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Prevention of HIV/AIDS
Prevention of HIV/AIDS
Prevention of HIV/AIDS
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HIV prevention refers to practices that aim to prevent the spread of the human immunodeficiency virus (HIV). HIV prevention practices may be undertaken by individuals to protect their own health and the health of those in their community, or may be instituted by governments and community-based organizations as public health policies.

Prevention strategies

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Interventions for the prevention of HIV include the use of:

AIDS Prevention - Condom dispensers in toilets

The consistent, correct use of condoms is one proven method for preventing the spread of HIV during sexual intercourse.[6] In high income countries, Prevention of Mother to Child Transmission Programs (PMTC) including HIV testing of pregnant women, antiretroviral treatment,[7] counselling about infant feeding, and safe obstetric practices (avoiding invasive procedures) have reduced mother-to-child transmission to less than 1%.

Treatment as prevention (TasP) is also effective; in sero-different couples (where one partner is HIV-positive and the other is HIV negative), HIV is significantly less likely to be transmitted to the uninfected partner if the HIV positive partner is on treatment.[8] It is now known that an if HIV-positive person has an undetectable viral load, there is no risk of HIV transmission to a sexual partner.[9][10][11]

Increased risk of contracting HIV correlates with the presence of co-infections, particularly other sexually transmissible infections. Medical professionals recommend treatment or prevention of other infections such as herpes, hepatitis A, hepatitis B, hepatitis C, human papillomavirus, syphilis, gonorrhea, and tuberculosis as an indirect way to prevent the spread of HIV infection. Doctors treat these conditions with pharmaceutical interventions and/or vaccination.[12] Nevertheless, it is not known if treating other sexually transmitted infections on a population scale is effective in preventing HIV.[13]

Harm reduction and social strategies

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Harm reduction is defined as "policies, programmes and practices that aim to minimise negative health, social and legal impacts associated with drug use, drug policies and drug laws".[14] The World Health Organization (WHO) recognizes that harm reduction is central to the prevention of HIV amongst people who inject drugs (PWID) and their sexual and drug using partners.[15] Social strategies do not require any drug or object to be effective, but rather require persons to change their behaviors to gain protection from HIV. Some social strategies include:[citation needed]

Each of these strategies has widely differing levels of efficacy, social acceptance, and acceptance in the medical and scientific communities.[citation needed]

Populations who access HIV testing are less likely to engage in behaviors with high risk of contracting HIV,[16] so HIV testing is almost always a part of any strategy to encourage people to change their behaviors to become less likely to contract HIV. Over 60 countries impose some form of travel restriction, either for short or long-term stays, for people infected with HIV.[17]

Advertising and campaigns

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Persuasive messages delivered through health advertising and social marketing campaigns which are designed to educate people about the risks of HIV/AIDS and simple prevention strategies are also an important way of preventing HIV. These persuasive messages have successfully increased people's knowledge about HIV. More importantly, information sent out through advertising and social marketing also proves to be effective in promoting more favorable attitudes and intentions toward future condom use, though they did not bring significant change in actual behaviors except those were targeting at specific behavioral skills.[18][19]

A 2020 systematic review of 16 studies found that financial education improved self-efficacy and lowered vulnerability to HIV in young people in low and middle income countries. Many of the studies in the review combined financial education with sexual health education and/or counselling.[20]

Research in health communication also found that importance of advocating critical skills and informing available resources are higher for people with lower social power, but not necessarily true for people with more power. African American audiences need to be educated about strategies they could take to efficiently manage themselves in health behaviors such as mood control, management of drugs, and proactive planning for sexual behaviors. However, these things are not as important for European Americans.[19]

Sexual contact

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Condoms and gels

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Condom in the shape of an AIDS ribbon
Various personal lubricants

Consistent condom use reduces the risk of heterosexual HIV transmission by about 80% over the long-term.[21] Where one partner of a couple has HIV infection, consistent condom use results in rates of HIV infection for the uninfected person below 1% per year.[22] Some data support the equivalence of internal condoms to latex condoms, but the evidence is not definitive.[23] As of January 2019, condoms are available inside 30% of prisons globally.[24] Use of the spermicide nonoxynol-9 may increase the risk of transmission because it causes vaginal and rectal irritation.[25] A vaginal gel containing tenofovir, a reverse transcriptase inhibitor, when used immediately before sex, was shown to reduce infection rates by roughly 40% among African women.[26]

Voluntary male circumcision

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South Africa 1 millionth voluntary medical male circumcision

Studies conducted in sub-Saharan Africa have found that circumcision reduces the risk of HIV infection in heterosexual men between 38 and 66% over two years.[27] Based on these studies, the World Health Organization and UNAIDS both recommended male circumcision as a method of preventing female-to-male HIV transmission in 2007.[28] Whether it protects against male-to-female transmission is disputed[29][30] and whether it is of benefit in developed countries and among men who have sex with men is undetermined.[31][32][33] For men who have sex with men there is some evidence that the penetrative partner has a lower chance of contracting HIV.[34] Some experts fear that a lower perception of vulnerability among circumcised men may result in more sexual risk-taking behavior, thus negating its preventive effects.[35] Women who have undergone female genital cutting have an increased risk of HIV.[36]

The African studies on which this information is based have been criticized for methodological flaws.[37] Svoboda and Howe compare them to the "lowest common denominator", citing "selection bias, randomization bias, experimenter bias, inadequate blinding, participant expectation bias, lack of placebo control, inadequate equipoise, excessive attrition of subjects, failure to investigate non-sexual HIV transmission, lead time bias, and time-out discrepancy." In addition, the 60% figure for risk reduction is dismissed as relative and misleading, with an absolute figure of only 1.3%, which is considered effectively meaningless given the "background noise produced by numerous sources of bias". They also point out that the United States has both the highest rates of circumcision and HIV/STD infections in the industrialized world, casting serious doubt that the former prevents the latter. There are also major epidemiological differences between regions: in Africa, HIV is commonly spread via inadequate infection prevention practices in health clinics, while in the US, the primary routes of infection are sharing equipment amongst people who use drugs and condomless anal intercourse among MSM. Additional criticisms are offered by George Hill:[38] "Our results clearly show that these African CRFs were methodologically flawed from start to finish... From the start, there was almost nothing correct with these studies. It was quite clear that these studies were unethical. They would never have been approved by a single ethics committee in the United States."

Education and health promotion

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Programs encouraging sexual abstinence do not appear to affect subsequent HIV risk in high-income countries.[39] Evidence for a benefit from peer education is equally poor.[40] Comprehensive sexual education provided at school may decrease high risk behavior.[41] A substantial minority of young people continue to engage in high-risk practices despite HIV/AIDS knowledge, underestimating their own risk of becoming infected with HIV.[42]

Before exposure

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Early treatment of HIV-infected people with antiretrovirals protected 96% of partners from infection.[43][8] Pre-exposure prophylaxis with a daily dose of tenofovir with or without emtricitabine is effective in a number of groups, including men who have sex with men, couples where one is HIV positive, and young heterosexuals in Africa.[26] Within the MSM community, the greatest barrier to PrEP use has been the stigma surrounding HIV and gay men. Gay men on PrEP have experienced "slut-shaming".[44][45] Numerous other barriers were identified, including lack of quality LGBTQ care, cost, and adherence to medication use.[citation needed]

Universal precautions within the health-care environment are believed to be effective in decreasing the risk of HIV.[46] Intravenous drug use is an important risk factor and harm reduction strategies such as needle-exchange programmes and opioid substitution therapy appear effective in decreasing this risk.[47]

Needle exchange programs (also known as syringe exchange programs) are effective in preventing HIV among IDUs and in the broader community.[48] Pharmacy sales of syringes and physician prescription of syringes have been also found to reduce HIV risk.[49] Supervised injection facilities are also understood to address HIV risk in the most-at-risk populations.[50] Multiple legal and attitudinal barriers limit the scale and coverage of these "harm reduction" programs in the United States and elsewhere around the world.[50]

The American Centers for Disease Control and Prevention (CDC) conducted a study in partnership with the Thailand Ministry of Public Health to ascertain the effectiveness of providing people who inject drugs illicitly with daily doses of the antiretroviral drug tenofovir as a prevention measure. The results of the study revealed a 48.9% reduced incidence of the virus among the group of subjects who received the drug, in comparison to the control group who received a placebo. The principal investigator of the study stated in the Lancet medical journal: "We now know that pre-exposure prophylaxis can be a potentially vital option for HIV prevention in people at very high risk for infection, whether through sexual transmission or injecting drug use."[51]

After exposure

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A course of antiretrovirals administered within 48 to 72 hours after exposure to HIV-positive blood or genital secretions is referred to as post-exposure prophylaxis.[52] The use of the single agent zidovudine reduces the risk of subsequent HIV infection fivefold following a needle stick injury.[52] Treatment is recommended after sexual assault when the perpetrators are known to be HIV positive, but is controversial when their HIV status is unknown.[53] Current treatment regimens typically use lopinavir/ritonavir and lamivudine/zidovudine or emtricitabine/tenofovir and may decrease the risk further.[52] The duration of treatment is usually four weeks[54] and is associated with significant rates of adverse effects (for zidovudine about 70% including: nausea 24%, fatigue 22%, emotional distress 13%, and headaches 9%).[55]

Follow-up care

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Strategies to reduce recurrence rates of HIV have been successful in preventing reinfection. Treatment facilities encourage those previously treated for HIV return to ensure that the infection is being successfully managed. New strategies to encouraging retesting have been the use of text messaging and email. These methods of recall are now used along with phone calls and letters.[56]

Mother-to-child

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Programs to prevent the transmission of HIV from mothers to children can reduce rates of transmission by 92–99%.[47][57] This primarily involves the use of a combination of antivirals during pregnancy and after birth in the infant but also potentially include bottle feeding rather than breastfeeding.[57][58] If replacement feeding is acceptable, feasible, affordable, sustainable and safe mothers should avoid breast-feeding their infants; however, exclusive breast-feeding is recommended during the first months of life if this is not the case.[59] If exclusive breast feeding is carried out the provision of extended antiretroviral prophylaxis to the infant decreases the risk of transmission.[60]

Vaccination

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Various approaches for HIV vaccine development

As of 2020, no effective vaccine for HIV or AIDS is known.[61] A single trial of the vaccine RV 144 found a partial efficacy rate around 30% and has stimulated optimism in the research community regarding developing a truly effective vaccine.[62] Further trials of the vaccine are ongoing.[63][64]

Gene therapy

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Certain mutations on the CCR5 gene have been known to make certain people unable to catch AIDS. Modifying the CCR5 gene using gene therapy can thus make people unable to catch it either.[65][66]

[edit]

Laws criminalizing HIV transmission have not been found an effective way to reduce HIV risk behavior, and may actually do more harm than good. In the past, many U.S. states criminalized the possession of needles without a prescription, even going so far as to arrest people as they leave private needle-exchange facilities.[67] In jurisdictions where syringe prescription status presented a legal barrier to access, physician prescription programs had shown promise in addressing risky injection behaviors.[68] Epidemiological research demonstrating that syringe access programs are both effective and cost-effective helped change state and local laws relating to needle-exchange program (NEP) operations and the status of syringe possession more broadly.[69] As of 2006, 48 states in the United States authorized needle exchange in some form or allowed the purchase of sterile syringes without a prescription at pharmacies.[70]

Removal of legal barriers to operation of NEPs and other syringe access initiatives has been identified as an important part of a comprehensive approach to reducing HIV transmission among injection drug users (IDUs).[69] Legal barriers include both "law on the books" and "law on the streets", i.e., the actual practices of law enforcement officers,[71][72] which may or may not reflect the formal law. Changes in syringe and drug-control policy can be ineffective in reducing such barriers if police continue to treat syringe possession as a crime or participation in NEP as evidence of criminal activity. [73] Although most NEPs in the US are now operating legally, many report some form of police interference.[73]

Research elsewhere has shown similar misalignment between "law on the books" and "law on the streets". For example, in Kyrgyzstan, although sex work, syringe sales, and possession of syringes are not criminalized and possession of small drug amounts has been decriminalized, gaps remain between these policies and law enforcement knowledge and practice.[74][75] To optimize public health efforts targeting vulnerable groups, law enforcement personnel and public health policies should be closely aligned. Such alignment can be improved through policy, training, and coordination efforts.[75]

Quality in prevention

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The EU-wide Joint Action on Improving Quality in HIV Prevention is seeking to increase the effectiveness of HIV prevention in Europe by using practical quality assurance (QA) and quality improvement (QI) tools.[76]

History

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1980s

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The Centers for Disease Control was the first organization to recognize the pandemic which came to be called AIDS.[77] Their announcement came on June 5, 1981, when one of their journals published an article reporting five cases of pneumonia, caused by Pneumocystis jirovecii, all in gay men living in Los Angeles.[78][79]

In May 1983, scientists isolated a retrovirus which was later called HIV from an AIDS patient in France.[80] At this point, the disease called AIDS was proposed to be caused by HIV, and people began to consider prevention of HIV infection as a strategy for preventing AIDS.[citation needed]

In the 1980s, public policy makers and most of the public could not understand that the overlap of sexual and needle-sharing networks with the general community had somehow lead to many thousands of people worldwide becoming infected with HIV.[77] In many countries, leaders and most of the general public denied both that AIDS and the risk behaviors which spread HIV existed outside of concentrated populations.[77]

In 1987, the United States FDA approved AZT as the first pharmaceutical treatment for AIDS.[81] Around the same time, ACT UP was formed, with one of the group's first goals being to find a way to get access to pharmaceutical drugs to treat HIV.[82] When AZT was made publicly available, it was extremely expensive and unaffordable to all but the most wealthy AIDS patients.[83] The availability of medicine but the lack of access to it sparked large protests around FDA offices.[84][85]

From 2003

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In 2003, Swaziland and Botswana reported nearly four out of 10 people were HIV positive.[86] Festus Mogae, president of Botswana, admitted huge infrastructure problems to the international community and requested foreign intervention in the form of consulting in health care setup and antiretroviral drug distribution programs.[87] In Swaziland, the government chose not to immediately address the problem in the way that international health agencies advised, so many people died.[88] In world media, the governments of African countries began to similarly be described as participating in the effort to prevent HIV actively or less actively.

There came to be international discussion about why HIV rates in Africa were so high, because if the cause were known, then prevention strategies could be developed. Previously, some researchers had suggested that HIV in Africa was widespread because of unsafe medical practices which somehow transferred blood to patients through procedures such as vaccination, injection, or reuse of equipment. In March 2003, the WHO released a statement that almost all infections were, in fact, the result of unsafe practices in heterosexual intercourse.[89]

In response to the rising HIV rates, Cardinal Alfonso López Trujillo, speaking on behalf of the Vatican, said that not only was the use of condoms immoral, but also that condoms were ineffective in preventing HIV.[90] The cardinal was highly criticized by the world health community, who were trying to promote condom use as a way to prevent the spread of HIV.[91][92] The WHO later conducted a study showing that condoms are 90% effective at preventing HIV.[90]

In 2001, the United States began a war in Afghanistan related to fighting the Taliban. The Taliban, however, had opposed local opium growers and the heroin trade; when the government of Afghanistan fell during the war, opium production was unchecked. By 2003, the world market had an increase in the available heroin supply; in former Soviet states especially, an increase in HIV infection was due to injection drug use. Efforts were renewed to prevent HIV related to sharing needles.[93][94][95][96]

From 2011

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In July 2011, it was announced by the WHO and UNAIDS that a once-daily antiretroviral tablet could significantly reduce the risk of HIV transmission in heterosexual couples.[97] These findings were based on the results of two trials conducted in Kenya and Uganda, and Botswana.

The Partners PrEP (pre-exposure prophylaxis) trial was funded by the Bill & Melinda Gates Foundation[98] and conducted by the International Clinical Research Center at the University of Washington. The trial followed 4758 heterosexual couples in Kenya and Uganda, in which one individual was HIV positive and the other was HIV negative.[97] The uninfected (HIV negative) partner was given either a once-daily tenofovir tablet, a once-daily combination tablet of tenofovir and emtricitabine, or a placebo tablet containing no antiretroviral drug. These couples also received counselling and had access to free male and female condoms. In couples taking tenofovir and tenofovir/emtricitabine, there was a 62% and 73% decrease, respectively, in the number of HIV infections as compared to couples who were receiving the placebo.[97]

A similar result was observed with the TDF2 trial, conducted by the United States Centers for Disease Control in partnership with the Botswana Ministry of Health.[99] The trial followed 1200 HIV negative men and women in Francistown, Botswana, a city known to have one of the world's highest HIV infection rates.[99] Participants received either a once-daily tenofovir/emtricitabine combination tablet or a placebo. In those taking the antiretroviral treatment, there was found to be a 63% decrease in the risk of acquiring HIV, as compared to those receiving the placebo.[97]

The HIV-1 virus has proved to be tenacious, inserting its genome permanently into patients' DNA, forcing patients to take a lifelong drug regimen to control the virus and prevent a fresh attack. Now, a team of Temple University School of Medicine researchers have designed a way to "snip out" the integrated HIV-1 genes for good. This is one important step on the path toward a permanent cure for AIDS. This is the first successful attempt to eliminate latent HIV-1 virus from human cells.

In a study published by the Proceedings of the National Academy of Sciences (PNAS), Khalili and colleagues detail how they created molecular tools to delete the HIV-1 proviral DNA.[full citation needed] When deployed, a combination of DNA-snipping enzyme called a nuclease and targeting strand of RNA called a guide RNA (gRNA) hunt down the viral genome and excise the HIV-1 DNA. From there, the cell's own gene repair machinery takes over, soldering the loose ends of the genome back together – resulting in virus-free cells.[citation needed]

Since HIV-1 is never cleared by the immune system, removal of the virus is required in order to cure the disease. The same technique could theoretically be used against a variety of viruses. The research shows that these molecular tools also hold promise as a therapeutic vaccine; cells armed with the nuclease-RNA combination proved impervious to HIV infection.

See also

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References

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Revisions and contributorsEdit on WikipediaRead on Wikipedia

Prevention of HIV/AIDS

View on Grokipedia
from Grokipedia
Prevention of HIV/AIDS comprises biomedical, behavioral, and public health interventions designed to block transmission of the human immunodeficiency virus (HIV), which progressively destroys CD4+ T cells and leads to acquired immunodeficiency syndrome (AIDS) if untreated. HIV spreads primarily through unprotected vaginal or anal intercourse, sharing of contaminated needles or syringes, and vertical transmission from mother to child during pregnancy, birth, or breastfeeding, requiring direct exchange of infected bodily fluids such as blood, semen, vaginal secretions, or breast milk with mucosal surfaces or the bloodstream. Key preventive measures include barrier methods like consistent and correct condom use during sex, pre-exposure prophylaxis (PrEP) with daily oral antiretrovirals for high-risk individuals, voluntary medical male circumcision for heterosexual men in high-prevalence areas, treatment as prevention (TasP) achieving viral suppression in people living with HIV, and harm reduction for injection drug use via sterile needle provision and opioid substitution therapy. Randomized controlled trials in sub-Saharan Africa established that voluntary medical male circumcision reduces heterosexual HIV acquisition in men by approximately 60%, prompting WHO recommendations and over 27 million procedures since 2007. PrEP demonstrates up to 99% efficacy against sexual transmission when adherence is high, though real-world effectiveness diminishes with inconsistent use, highlighting the need for adherence support.00116-5/fulltext) TasP, supported by cohort studies showing zero linked transmissions from virally suppressed individuals during condomless sex, has contributed to declining incidence in treated populations. Despite these evidence-based advances, prevention faces challenges from behavioral risks, access barriers in low-resource settings, and incomplete coverage, with no licensed vaccine available after decades of research.

Behavioral and Lifestyle Prevention

Abstinence, Monogamy, and Partner Selection

Sexual abstinence from vaginal and anal intercourse completely eliminates the risk of HIV transmission through these routes, as the virus requires direct contact with infected bodily fluids such as blood, semen, or vaginal secretions during such activities. This method relies on no penetrative sex occurring, rendering it 100% effective when adhered to, independent of viral load or other factors.30307-2/fulltext) Oral sex carries negligible risk, with no confirmed cases of HIV transmission solely via this route in systematic reviews. Monogamous relationships, defined as exclusive sexual partnering between two HIV-negative individuals with verified status through testing, similarly confer zero risk of sexual transmission, as no exposure to the virus occurs. In serodiscordant couples (one partner HIV-positive), transmission risk persists despite monogamy, with per-coital-act probabilities ranging from 0.0001 (low viral load <1,700 copies/mL) to 0.0023 (high viral load ≥38,500 copies/mL) for heterosexual acts, accumulating over time without suppression.04331-2/abstract) Long-term mutual fidelity has been linked to population-level declines, as evidenced in Uganda where reductions in casual partnerships—promoted via fidelity messaging—correlated with HIV prevalence dropping from approximately 15-30% in the early 1990s to under 6% by 2005, primarily through behavioral shifts rather than condom use alone. Partner selection strategies, such as choosing individuals with low-risk profiles (e.g., no history of multiple partners, injection drug use, or sexually transmitted infections), further mitigate risk by avoiding exposure to higher-prevalence networks. Serosorting—limiting unprotected sex to partners perceived as HIV-negative—offers partial protection, reducing acquisition risk by less than 50% compared to unknown or discordant partners, but is undermined by testing gaps, window periods, and undiagnosed infections. Regular mutual testing and disclosure enhance efficacy, though reliance on self-reported status introduces inaccuracies, as studies show 19% HIV prevalence among self-identified monogamous women in high-burden areas due to undisclosed infidelity or prior infections. These behavioral approaches, when combined, outperform inconsistent barrier methods in causal models of transmission dynamics, emphasizing sustained commitment over episodic interventions.

Risk-Averse Sexual Practices

Risk-averse sexual practices for HIV prevention emphasize selecting activities, positions, and partner dynamics that inherently lower the probability of transmission per sexual encounter, independent of barriers or pharmacological interventions. These strategies leverage empirical data on per-act transmission risks, which vary significantly by exposure type: receptive anal intercourse carries the highest risk at approximately 1.38% (138 per 10,000 acts) for the receptive partner when the insertive partner is untreated and HIV-positive, followed by insertive anal at 0.11% (11 per 10,000 acts), receptive penile-vaginal at 0.08% (8 per 10,000 acts), and insertive penile-vaginal at 0.04% (4 per 10,000 acts). Oral sex poses negligible risk, estimated at 0 to 4 per 10,000 acts across studies; however, using barriers such as condoms or dental dams can further minimize this low risk. High-risk individuals engaging in oral sex may consider pre-exposure prophylaxis (PrEP) for added protection. If exposure is suspected, prompt consultation with a medical professional for HIV testing is advised, with detection typically possible around 4 weeks post-exposure depending on the test used. Oral sex also transmits other sexually transmitted infections, such as syphilis, gonorrhea, and HPV, more readily than HIV, underscoring the importance of regular screening. Meta-analyses confirm that anal intercourse transmits HIV at rates 10 to 20 times higher than vaginal intercourse, primarily due to thinner rectal mucosa, greater susceptibility to microtears, and higher viral shedding in rectal fluids compared to vaginal or cervical secretions. Receptive roles amplify risk across both anal and vaginal acts, as they involve greater exposure to pre-ejaculate, semen, or menstrual blood containing the virus. Thus, HIV-negative individuals can reduce exposure by prioritizing insertive over receptive positions, vaginal or oral over anal intercourse, and limiting acts to those with lower baseline probabilities, particularly with partners of unknown or positive status. Serosorting—selecting partners of concordant HIV-negative status based on self-reported or tested knowledge—offers partial risk reduction for negatives, with observational data indicating up to a 12% lower odds of seroconversion compared to partnering with those of unknown or discordant status, though effectiveness drops below 50% when accounting for disclosure inaccuracies or undiagnosed infections. This practice's limitations are pronounced during acute HIV infection, when viral loads peak and transmission risk surges 10- to 26-fold, often preceding detectable antibodies or symptoms; serosorting fails here if partners are in this window, contributing to clusters among men who have sex with men (MSM). Strategic positioning, where HIV-positive individuals assume insertive roles to minimize partner exposure, similarly yields modest benefits but does not eliminate risk without viral suppression. Cumulative risk escalates with repeated exposures, underscoring the value of minimizing high-risk acts even in seroconcordant scenarios; for instance, consistent preference for low-risk practices can avert infections where per-act probabilities compound over time. These approaches, while evidence-based, require accurate status awareness and do not substitute for comprehensive strategies, as real-world adherence often underperforms idealized models due to behavioral inconsistencies.

Substance Use Avoidance and Injection Risk Reduction

Injection drug use contributes significantly to HIV transmission through the sharing of contaminated needles and syringes, which directly exposes users to infected blood. In the United States, approximately 7% of new HIV infections in 2022 were attributed to people who inject drugs (PWID), with men accounting for 4% and women for 3% of these cases. Globally, an estimated 1.4 million PWID live with HIV, representing about 1 in 8 injectors. The per-act risk of HIV transmission from a needlestick injury involving HIV-positive blood is approximately 0.23%, though cumulative risk escalates with repeated sharing, as evidenced by higher HIV prevalence among frequent sharers—up to 44% in some street-based cohorts. Complete avoidance of injection drug use eliminates the risk of HIV acquisition via this route, providing 100% protection against injection-related transmission. Empirical data from treatment programs underscore that sustained abstinence, achieved through pharmacological and behavioral interventions, prevents new infections by curtailing exposure opportunities entirely. For instance, entry into substance use treatment, including relapse prevention strategies, has been linked to zero injection-related HIV incidents among completers, contrasting with ongoing risks for active users. While comprehensive drug dependence treatment—encompassing detoxification, counseling, and long-term support—demonstrates efficacy in reducing HIV risk behaviors across various injected substances like heroin, cocaine, and amphetamines, its success hinges on adherence and access barriers. For PWID unable or unwilling to cease injection immediately, harm reduction measures aim to minimize sharing while ideally facilitating transition to abstinence-oriented care. Needle and syringe programs (NSPs), which provide sterile equipment, are associated with reduced receptive needle-sharing behaviors and HIV seroconversion in meta-analyses of observational data; one review of high-validity studies reported a protective effect against HIV incidence, though outcomes vary by program scale and complementary interventions. Systematic reviews indicate NSPs correlate with up to 50% reductions in HIV transmission in some contexts, without evidence of increased drug initiation or use prevalence, but they do not consistently promote cessation and may require integration with treatment to maximize impact. Opioid substitution therapy (OST), such as methadone or buprenorphine maintenance, further mitigates injection risks by substituting oral administration for injecting, thereby reducing frequency of use and sharing. A Cochrane systematic review found OST associated with a 54% reduction in HIV transmission risk among PWID (rate ratio 0.46, 95% CI 0.32-0.67), supported by lowered drug- and sex-related risk behaviors in diverse populations. Meta-analyses confirm OST enhances antiretroviral therapy adherence and HIV care continuum outcomes, halving injection-related exposures without exacerbating overall substance use when combined with psychosocial support. However, effectiveness diminishes with suboptimal dosing or retention, and access remains limited in many regions, underscoring the need for abstinence-focused alternatives where feasible.

Physical and Mechanical Barriers

Condom Efficacy and Usage Challenges

Condoms, when used consistently and correctly, reduce the risk of HIV transmission during heterosexual intercourse by approximately 80% among serodiscordant couples, according to a meta-analysis of prospective studies. Estimates of effectiveness vary, with some reviews placing it between 60% and 96%, reflecting differences in study designs and populations, but consistent use does not eliminate transmission risk entirely due to potential viral exposure from pre-ejaculate or micro-tears. In laboratory conditions, intact latex condoms provide a barrier impermeable to HIV particles, yet real-world efficacy diminishes significantly with typical use patterns. Usage challenges arise primarily from errors in application and maintenance, which compromise protective efficacy. Common issues include breakage, occurring in 1-3% of uses during vaginal or anal intercourse, and slippage, reported in 2-13% of instances, often due to improper sizing, inadequate lubrication, or premature withdrawal without holding the base. Incomplete use—such as delayed application after initial penetration or removal before completion—exacerbates risks, with self-reported errors affecting up to 40% of condom-protected encounters in observational data. In anal intercourse, particularly among men who have sex with men, higher friction increases breakage rates to 3-5%, underscoring the need for water-based lubricants to mitigate tears. Behavioral and contextual factors further hinder consistent adoption. Alcohol or substance intoxication impairs judgment, leading to skipped use or mishandling, while long-term relationships foster complacency, reducing adherence even in high-risk serodiscordant pairs. Cultural, religious, or stigma-related barriers, including perceptions of reduced pleasure or emasculation, contribute to non-use, as documented in surveys from diverse regions. Interventions like counseling and demonstrations can halve breakage rates by improving skills, yet sustained compliance remains low, with meta-analyses showing inconsistent use in over 50% of sexually active HIV-positive individuals in sub-Saharan Africa. These challenges highlight that while condoms offer substantial protection, their preventive impact depends on addressing human factors beyond mechanical reliability.

Male Circumcision Evidence and Debates

Three randomized controlled trials (RCTs) conducted in high HIV-prevalence regions of sub-Saharan Africa demonstrated that voluntary medical male circumcision (VMMC) reduces the risk of HIV acquisition in heterosexual men by approximately 60%. The first trial in South Africa (2005) reported a 60% reduction in HIV incidence among circumcised men compared to uncircumcised controls over 21 months. Similar results emerged from trials in Kenya (2007) and Uganda (2007), with hazard ratios indicating 51-60% protective efficacy, leading to early trial termination due to evident benefit. These findings prompted WHO and UNAIDS in 2007 to recommend VMMC as an additional strategy for HIV prevention in 15 priority countries in eastern and southern Africa, where heterosexual transmission predominates. Subsequent observational studies and meta-analyses have corroborated the RCTs, estimating a consistent 50-60% reduction in HIV risk for circumcised men engaging in vaginal sex. A 2021 meta-analysis of studies on risk behavior found no evidence of risk compensation—increased sexual activity offsetting the protective effect—among heterosexual men post-circumcision. By 2023, over 27 million VMMCs had been performed in priority countries, with modeling estimating up to 83,000 HIV infections averted from 2010 onward. Biological mechanisms include removal of the foreskin, which harbors Langerhans cells susceptible to HIV entry, and reduced viral shedding in circumcision wounds or semen. Debates center on generalizability beyond high-prevalence African settings with primarily heterosexual transmission. Critics argue that VMMC is not a "panacea," requiring integration with behavioral interventions, and note low uptake due to cultural resistance or misconceptions about complete protection. Evidence for protection of female partners is mixed; a 2014 Ugandan study found women with circumcised partners had lower HIV prevalence, but RCTs like the Partners PrEP trial showed no significant reduction in female acquisition rates. For men who have sex with men (MSM), where anal transmission dominates, observational meta-analyses suggest a 23% overall HIV risk reduction, stronger for insertive roles, but RCTs are lacking and WHO does not routinely recommend VMMC for this group. In low-prevalence areas like the US or Europe, where MSM drive epidemics, public health modeling indicates limited population-level impact. Adverse events from VMMC are rare (1-2% moderate/severe), mostly resolving without sequelae, supporting safety in resource-limited settings. Ethical concerns include informed consent for minors and potential coercion in campaigns, though voluntary adult/ adolescent programs emphasize autonomy. Some opponents question trial validity, citing early stopping or self-reported behaviors, but independent analyses affirm methodological rigor and causal efficacy via direct intervention effects. Overall, while VMMC complements but does not replace condoms or PrEP, empirical data substantiate its role in targeted heterosexual epidemics.

Pharmacological and Biomedical Interventions

Pre-Exposure Prophylaxis (PrEP) Including Long-Acting Options

Pre-exposure prophylaxis (PrEP) refers to the use of antiretroviral medications by HIV-uninfected individuals at substantial risk of acquisition to prevent infection upon potential exposure. The primary oral regimen consists of daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, branded as Truvada), approved by the U.S. Food and Drug Administration (FDA) for this indication in July 2012 following demonstration of efficacy in clinical trials among men who have sex with men (MSM) and heterosexual serodiscordant couples. When adhered to consistently, oral PrEP reduces HIV acquisition risk from sexual exposure by approximately 99% and from injection drug use by at least 74%, though real-world effectiveness diminishes with suboptimal adherence, often falling below trial levels due to inconsistent pill-taking. High adherence (>80% of doses) correlates with near-complete protection, as evidenced by nested analyses in trials like Partners PrEP, underscoring the causal role of sustained drug levels in blocking viral replication during early exposure. Alternative oral formulations include emtricitabine/tenofovir alafenamide (FTC/TAF, Descovy), approved for PrEP in 2019, which offers similar efficacy with potentially lower risks of tenofovir-related renal and bone toxicity compared to TDF-based regimens. On-demand dosing (e.g., two pills 2-24 hours before sex followed by one daily for two days) is supported for MSM but not recommended for vaginal sex or injection drug use due to pharmacokinetic differences. Common side effects of oral PrEP include gastrointestinal intolerance (e.g., nausea, diarrhea in ~15% of users) and fatigue, with rare but monitored risks of lactic acidosis, renal impairment, or hepatitis B reactivation upon discontinuation. Quarterly HIV testing, creatinine monitoring, and counseling on adherence and risk behaviors are required for safe use, as undetected infection can lead to antiretroviral resistance. Long-acting injectable options address adherence barriers inherent to daily oral therapy. Cabotegravir long-acting (CAB-LA, Apretude), an integrase strand transfer inhibitor administered intramuscularly every two months after initial loading doses, demonstrated superior HIV prevention efficacy over daily FTC/TDF in phase 3 trials among MSM and transgender women, with incidence rates of 0.15% versus 0.68% and real-world data confirming >99% effectiveness in diverse cohorts. FDA approval occurred in December 2021, with post-trial open-label extensions maintaining low incidence (0.07%) over four years. Injection-site reactions occur in up to 80% of recipients but are mostly mild and transient; rare integrase inhibitor resistance has been noted in breakthrough cases. Emerging ultra-long-acting PrEP includes subcutaneous lenacapavir, a capsid inhibitor administered every six months, which received CDC recommendation in September 2025 for high-risk individuals following trials showing superior efficacy to oral and CAB-LA options, with HIV incidence reductions exceeding 96% in diverse populations. This biannual regimen minimizes adherence demands while preserving high drug concentrations, though implementation challenges include higher costs and the need for specialized administration. Overall, PrEP's population-level impact depends on targeting high-incidence groups, overcoming access barriers like cost (e.g., ~$2,000/month for branded orals without assistance), and integrating with testing and behavioral strategies, as suboptimal real-world uptake limits broader incidence declines.

Post-Exposure Prophylaxis (PEP)

Post-exposure prophylaxis (PEP) consists of a 28-day course of antiretroviral medications initiated after a potential HIV exposure to prevent infection establishment. The regimen must begin as soon as possible, ideally within 2 hours but no later than 72 hours post-exposure, as efficacy diminishes beyond this window based on viral replication dynamics observed in animal models and human pharmacokinetics. Indications include high-risk events such as receptive anal intercourse with an HIV-positive partner, occupational needlestick injuries from viremic sources, or shared injection equipment with known HIV-infected individuals; decisions for unknown-source exposures require case-by-case risk assessment weighing exposure type, source viral load if available, and recipient factors like pre-existing hepatitis B or renal impairment. Preferred regimens involve three-drug combinations, typically a backbone of tenofovir disoproxil fumarate or tenofovir alafenamide plus emtricitabine or lamivudine, paired with an integrase strand transfer inhibitor such as dolutegravir or raltegravir for rapid viral suppression and tolerability. These selections prioritize agents with low resistance barriers, favorable pharmacokinetics for post-exposure use, and minimal drug interactions, as evidenced by updated 2025 U.S. Public Health Service guidelines incorporating newer antiretrovirals. Side effects are generally mild and self-limiting, including nausea, diarrhea, fatigue, headache, and rash, affecting a minority of users and rarely leading to discontinuation when managed supportively; severe reactions like lactic acidosis or hepatotoxicity are exceptional and linked to underlying conditions. Adherence to the full 28-day course is critical, though meta-analyses report completion rates around 57-90% in observational settings, influenced by counseling and follow-up. Efficacy data derive primarily from observational studies and animal models rather than randomized controlled trials, which are ethically infeasible due to withholding treatment from high-risk exposed individuals. A 1997 case-control study of occupational exposures found zidovudine monotherapy reduced HIV acquisition odds by 81% when started promptly. Network meta-analyses of randomized trials on regimen tolerability suggest integrase inhibitor-based PEP yields higher completion rates and lower seroconversion risks compared to older protease inhibitor options, with zero infections in small completion cohorts. Real-world reductions in transmission risk approximate 80% for adherent users in high-incidence scenarios, though incomplete data on non-adherent cases and confounding factors like source viral suppression limit precision; PEP does not eradicate established infection and fails if viral integration precedes full suppression. Post-PEP management includes HIV testing at baseline, 4-6 weeks, 3 months, and 6 months to detect rare delayed seroconversions, alongside screening for hepatitis B/C and sexually transmitted infections. During the course, individuals should avoid further exposures, such as condomless sex or needle sharing, and use additional barriers to mitigate secondary transmission risks if undiagnosed infection occurs. PEP originated from 1990s extrapolations of antiretroviral monotherapy successes, with formal nonoccupational guidelines emerging in the early 2000s following occupational precedents; 2025 updates reflect evolving drug safety profiles and emphasize rapid access via emergency departments or hotlines. Limitations include cost barriers in low-resource settings, potential for drug resistance if misused, and over-reliance as a substitute for primary prevention, underscoring the need for integrated counseling on abstinence, condoms, and PrEP for recurrent risks.

Antiretroviral Treatment as Prevention (TasP)

Antiretroviral treatment as prevention (TasP) involves administering antiretroviral therapy (ART) to individuals living with HIV to suppress their plasma viral load to undetectable levels, thereby dramatically reducing the risk of sexual transmission to uninfected partners. This approach leverages the causal relationship between viral load and transmissibility: higher viral loads correlate with increased transmission probability, while suppression below detectable thresholds—typically less than 200 copies per milliliter—eliminates viable virus in genital fluids and blood. Empirical data from randomized controlled trials and observational studies confirm that TasP achieves near-zero transmission risk when viral suppression is maintained, underpinning public health strategies like the "Undetectable = Untransmittable" (U=U) consensus. The landmark HPTN 052 trial, conducted from 2005 to 2015 across nine countries, enrolled 1,763 serodiscordant heterosexual couples and demonstrated that immediate ART initiation by the HIV-positive partner reduced linked transmissions by 93% compared to delayed initiation. In the immediate-ART arm, only one transmission occurred after viral suppression was achieved, yielding a 96% preventive efficacy attributable to treatment; no transmissions were observed during periods of confirmed undetectability. Subsequent analyses, including the PARTNER studies (2014–2018), extended this to diverse populations: across 1,166 serodiscordant couples (including men who have sex with men), zero transmissions were documented in 58,000 condomless sex acts when the HIV-positive partner maintained an undetectable viral load. A 2023 systematic review reinforced these findings, identifying no definitive evidence of transmission at viral loads below 600 copies per milliliter across multiple cohorts, though rare events at low detectable levels highlight the need for consistent suppression. Major health authorities endorse TasP as a core prevention pillar. The U.S. Centers for Disease Control and Prevention (CDC) recommends ART for all diagnosed individuals regardless of CD4 count, citing its dual benefit in preserving health and preventing onward transmission. Similarly, the World Health Organization (WHO) advocates universal ART access under the "treat all" policy since 2016, projecting up to 28% global incidence reduction by 2030 if scaled effectively. Real-world implementation, however, depends on achieving and sustaining viral suppression, which requires daily adherence rates exceeding 95% in most regimens; suboptimal adherence leads to viral rebound and restored transmissibility. Challenges to TasP efficacy include barriers to adherence, such as stigma, medication side effects, and socioeconomic factors, which undermine suppression in resource-limited settings. Drug resistance, arising from inconsistent use, can compromise both individual treatment and population-level prevention, necessitating resistance monitoring and optimized regimens. While TasP integrates well with other interventions like PrEP, its success hinges on robust testing, linkage to care, and retention—elements often faltering in high-burden regions despite empirical proof of biological efficacy.

Prevention of Mother-to-Child Transmission

Mother-to-child transmission (MTCT) of HIV occurs during pregnancy (intrauterine), labor and delivery (intrapartum), or breastfeeding (postnatal), with overall transmission rates of 15-45% in the absence of interventions, including approximately 5-8% intrauterine, 10-20% intrapartum, and 10-20% cumulative postnatal risk over 1-2 years of breastfeeding. Risk factors include high maternal viral load (>100,000 copies/mL), advanced maternal disease (low CD4 count), prolonged rupture of membranes, chorioamnionitis, preterm delivery, and breastfeeding without suppression of viral replication. Antiretroviral therapy (ART) administered to the mother throughout pregnancy, delivery, and postpartum periods is the cornerstone of prevention, reducing MTCT risk to less than 5% globally and under 1-2% in settings with comprehensive care, through mechanisms including lowering maternal viral load, placental protection, and pre-exposure for the infant. World Health Organization (WHO) guidelines recommend initiating lifelong triple-drug ART as early as possible in pregnancy for all women living with HIV, regardless of CD4 count or viral load, with regimens such as dolutegravir-based therapy preferred for efficacy and safety. U.S. Centers for Disease Control and Prevention (CDC) and National Institutes of Health (NIH) endorse similar oral ART continuation from preconception, with intrapartum intravenous zidovudine added if viral load exceeds 1,000 copies/mL near delivery. Randomized trials, including the Pediatric AIDS Clinical Trials Group 076 study, demonstrate that zidovudine alone reduces transmission by 66%, with triple ART achieving greater reductions, though early trials noted higher adverse outcomes like preterm birth that have diminished with modern regimens. For infants, postnatal prophylaxis with nevirapine or zidovudine, initiated within 6-12 hours of birth and continued for 4-6 weeks, further mitigates risk, particularly when combined with maternal ART, yielding transmission rates below 2% in adherent populations. Mode of delivery influences risk: vaginal birth is recommended if maternal viral load is suppressed below 1,000 copies/mL, while scheduled cesarean section at 38 weeks reduces intrapartum transmission by up to 50% if viral load remains higher despite ART. Postnatal feeding strategies vary by resource setting; in high-income contexts like the U.S., exclusive replacement feeding with formula is advised to eliminate breastfeeding-associated risk (estimated 0.3-1% per month if unsuppressed), whereas WHO permits ART-suppressed breastfeeding in low-resource areas where formula is unsafe, with infant prophylaxis extended to 6-12 weeks or longer. Early infant diagnosis via virologic testing (e.g., HIV DNA/RNA PCR) at birth, 4-6 weeks, and 4-6 months, followed by confirmatory antibody testing at 18 months, enables prompt ART initiation if infected, with global programs achieving MTCT reductions from 20-30% pre-ART era to under 5% where coverage exceeds 80%. Challenges persist in low-adherence settings, where incomplete ART uptake correlates with 3-11% residual transmission, underscoring the need for universal antenatal HIV testing and linkage to care.

Experimental and Emerging Approaches

Vaccine Development Efforts

Developing an effective vaccine against HIV has proven exceptionally challenging due to the virus's high mutation rate, which generates extensive genetic diversity, and its ability to evade immune detection by integrating into host DNA and suppressing key immune responses. Unlike many pathogens, HIV lacks natural sterilizing immunity in infected individuals, and no clear correlates of protection—such as specific antibody levels or T-cell responses—have been definitively established in humans. These factors, combined with the absence of an ideal animal model that fully recapitulates human infection, have hindered progress despite decades of research. Early efforts focused on recombinant envelope proteins like gp120 in the AIDSVAX trials (1998–2003), which failed to demonstrate efficacy against HIV acquisition in phase 3 studies involving over 5,000 participants in North America and Thailand. Adenoviral vector-based approaches, such as the STEP trial (2004–2007) using Merck's MRK Ad5 HIV-1 gag/pol/nef vaccine, not only failed to protect but showed increased infection risk in uncircumcised men with pre-existing Ad5 immunity, leading to trial halt. The RV144 trial (2003–2009) in Thailand, combining ALVAC prime with AIDSVAX boost, achieved modest 31.2% efficacy—the only positive signal in large-scale efficacy trials—but waned rapidly and lacked replication. Subsequent trials like HVTN 505 (DNA/adenovirus vectors, halted 2013) and Mosaico (2019–2023, mosaic immunogen in MSM/transgender populations) also failed, leaving no candidates in phase 3 as of 2023. Contemporary strategies emphasize inducing broadly neutralizing antibodies (bNAbs) targeting conserved HIV epitopes, often via germline-targeting immunogens to guide naive B cells toward mature bNAb lineages. In May 2025, two IAVI-led phase 1 trials demonstrated proof-of-concept for sequential vaccination priming bnAb precursors, published in Science, marking a potential pathway though long-term efficacy remains unproven. mRNA platforms, leveraging COVID-19 vaccine successes, showed potent CD4+ T-cell and antibody responses in early 2025 trials, addressing variable envelope immunogenicity. Other candidates include a Duke-developed vaccine activating bnAb pathways (January 2025), an Argonne-assisted immunogen neutralizing over one-third of U.S. strains (March 2025), and MIT's adjuvant-enhanced single-dose approach boosting B-cell responses in preclinical models (June 2025). A phase 1 trial of the GRAd-HIVNE1 gorilla adenovirus vector began in Africa in July 2025, focusing on conserved epitopes. As of October 2025, no HIV vaccine has been licensed, with efforts constrained by NIAID's May 2025 decision to defund major consortia, signaling funding uncertainties amid repeated trial failures. Phase 1 and 2 trials predominate, prioritizing bnAb induction and multi-clade coverage, but advancing to efficacy testing requires overcoming HIV's immune evasion and establishing durable protection—challenges unmet after over $20 billion invested globally since the 1980s.

Gene Editing and Therapeutic Strategies

Gene editing strategies for HIV prevention primarily target the CCR5 co-receptor, a key entry point for R5-tropic HIV strains that predominate in early infection. Individuals homozygous for the CCR5Δ32 mutation exhibit near-complete resistance to these strains due to the absence of functional CCR5 on cell surfaces, as evidenced by epidemiological data showing significantly lower HIV acquisition rates among such genotypes. This natural variant provides a first-principles basis for therapeutic editing: disrupting CCR5 expression in hematopoietic stem and progenitor cells (HSPCs) or T cells could generate HIV-resistant immune compartments, potentially preventing de novo infection in high-risk uninfected individuals or reducing transmission risk post-exposure. CRISPR-Cas9 has emerged as the dominant tool for CCR5 knockout, with preclinical studies demonstrating efficient editing in primary human T cells and HSPCs, conferring resistance to HIV challenge in vitro. For instance, dual-guide RNA approaches achieved up to 90% indel formation at CCR5 loci, protecting edited CD4+ T cells from R5- and X4-tropic HIV replication while unedited controls succumbed. In vivo, CRISPR-mediated CCR5 disruption combined with HIV proviral editing (targeting LTR-Gag regions) enabled viral clearance in antiretroviral-suppressed humanized mouse models, highlighting potential for sterilizing protection or reservoir elimination that indirectly aids prevention by halting progression to transmissibility. Multilayered edits, such as CCR5 knockout alongside CXCR4 disruption or fusion inhibitor expression (e.g., C46 peptide), further enhance resistance against diverse HIV tropisms, with edited cells showing sustained protection in challenge assays. Clinical translation remains nascent, with early-phase trials focusing on safety in HIV-infected patients rather than uninfected prophylaxis. A 2019 phase 1 study transplanted autologous CRISPR-edited CCR5-ablated HSPCs into an HIV+ patient with acute lymphoblastic leukemia, achieving multilineage engraftment without severe adverse events, though editing efficiency was modest (low allelic disruption rates) and long-term HIV resistance unproven due to concurrent conditioning and ART. Ongoing efforts, including EBT-101 (an AAV-delivered CRISPR system targeting HIV provirus and host factors), received FDA fast-track designation in 2023 for potential cure, with phase 1 data expected by 2025; while aimed at infected individuals, the approach could adapt for preventive editing in at-risk populations. Ex vivo lentiviral gene therapies, such as AGT103-T (encoding triple-function vectors for CCR5 knockdown, antiviral peptides, and immune enhancement), completed phase 1a dosing in HIV+ subjects by 2023, showing tolerability but requiring further efficacy readouts for resistance induction. Challenges include off-target edits, incomplete engraftment, and ethical barriers to germline editing, as seen in the 2018 He Jiankui controversy where CCR5 edits in embryos aimed at HIV resistance but yielded mosaicism and unintended mutations, underscoring risks without proven population-level benefits. Broader therapeutic strategies integrate gene editing with immunotherapies for enhanced prevention. CRISPR-enabled disruption of both CCR5 and HIV-1 genomes in T cells, paired with checkpoint inhibitors, has shown synergy in preclinical models for eliciting curative immune responses that could preclude establishment of infection. Autologous lymphocyte infusions post-editing (e.g., NCT04561258 trial) aim to expand resistant cell pools in virally suppressed patients, with implications for post-exposure boosting of immunity. However, scalability limitations—high costs, need for myeloablation, and variable editing fidelity—constrain deployment for widespread prevention, prioritizing high-burden cases over prophylactic use. Peer-reviewed data emphasize empirical hurdles like immune rejection of edited cells and incomplete tropism coverage (e.g., X4 strains evading CCR5 edits), necessitating multiplexed strategies for robust, verifiable protection.

Public Health Implementation

Education, Campaigns, and Behavioral Promotion

Education and public campaigns for HIV prevention emphasize behavioral modifications to reduce transmission risk, including delayed sexual initiation among youth, reduction in sexual partners, and consistent use of condoms during intercourse. The ABC strategy—abstinence for the unmarried, being faithful in sexual relationships, and correct and consistent condom use—has been a cornerstone of such efforts, particularly in sub-Saharan Africa. Empirical evaluations indicate that comprehensive programs integrating these elements, when delivered with adequate intensity and resources, effectively lower risk behaviors and HIV incidence. In Uganda, nationwide mobilization starting in the late 1980s promoted the ABC approach through school curricula, community outreach, religious leaders, and mass media, leading to substantial behavioral shifts: increased abstinence among adolescents, higher rates of monogamy, and greater condom awareness. HIV prevalence among adults fell from about 15% in 1992 to 5% by 2001, with studies attributing roughly two-thirds of the decline to these changes rather than solely biomedical factors. This success contrasted with regions relying predominantly on condom promotion, where prevalence reductions were less pronounced, highlighting the causal role of partner limitation and delayed debut in transmission dynamics. School-based HIV education programs have demonstrated moderate effectiveness in altering knowledge, attitudes, and behaviors among adolescents, particularly in low- and middle-income countries. A meta-analysis of such interventions found they reduce HIV-related risk behaviors, including unprotected sex and multiple partnerships, with effect sizes indicating sustained impacts when programs include skills training for negotiation and refusal. Peer-led initiatives further enhance outcomes by fostering normative shifts, with meta-analyses showing improved behavioral metrics like condom use consistency, though effects on biological endpoints like incidence vary by implementation fidelity. Mass media campaigns, including television, radio, and social marketing, contribute to heightened awareness and short-term increases in testing uptake but yield mixed results for long-term behavioral adherence. Reviews of U.S. and international efforts from the 1980s onward note gains in knowledge and stigma reduction, yet limited evidence for durable risk reduction without complementary community or interpersonal reinforcement. Targeted campaigns for high-risk groups, such as men who have sex with men or sex workers, often integrate messaging on partner testing and PrEP alongside behavioral promotion, though evaluations stress the need for culturally tailored content to counter risk compensation. Overall, sustained declines in transmission require integrating education with policy support, as isolated campaigns risk diminishing returns amid evolving social norms. International guidelines on HIV/AIDS and human rights, consolidated by the Office of the United Nations High Commissioner for Human Rights (OHCHR), advocate for public health laws that empower authorities to deliver comprehensive prevention services, including funding for testing, condoms, and harm reduction measures like needle exchange programs. The UNAIDS Global Strategy Framework coordinates United Nations responses by promoting proactive policies for epidemic control, emphasizing integration of prevention into broader health systems. The World Health Organization (WHO) guidelines, updated through 2025, endorse evidence-based interventions such as condom promotion, opioid substitution therapy, and clean injecting equipment to curb transmission, while calling for legal environments that reduce stigma and barriers to care. In July 2025, WHO specifically recommended injectable lenacapavir as a highly effective pre-exposure prophylaxis (PrEP) option, prioritizing its rollout in high-burden settings to enhance prevention efficacy. Major funding mechanisms underpin global access frameworks, with the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), launched in 2003, committing over $110 billion by 2025 to support prevention in 50+ countries, averting an estimated 5 million new infections through antiretroviral distribution and community programs. PEPFAR's bilateral efforts focus on 14 high-prevalence countries, integrating prevention with treatment to achieve 95-95-95 targets (95% diagnosed, 95% treated, 95% virally suppressed). However, in 2025, U.S. policy shifts under the Trump administration imposed stop-work orders and funding freezes on PEPFAR contracts, halting PrEP distribution in several African nations and projecting up to 1 million additional infections by 2030 if unresolved. Complementing this, the Global Fund to Fight AIDS, Tuberculosis and Malaria secured voluntary licensing for lenacapavir in July 2025, enabling affordable access in low- and middle-income countries prioritized by HIV incidence. Legal frameworks often intersect with prevention efficacy, particularly through HIV-specific criminalization statutes that penalize non-disclosure or exposure, present in over 30 U.S. states and numerous countries as of 2025. These laws, enacted largely before advances in undetectable viral load and PrEP, correlate with reduced testing uptake due to prosecution fears, undermining prevention by limiting early intervention and partner notification. UNAIDS reports that such criminalization exacerbates stigma, deterring care-seeking among key populations like men who have sex with men and people who inject drugs. Conversely, reform efforts, including UNAIDS' 2025 Road Map, promote decriminalization of sex work and same-sex conduct to enable primary prevention scaling, alongside policies mandating anonymous testing and removing age-of-consent barriers for adolescents. National policies in countries like South Africa integrate voluntary medical male circumcision into public health mandates, supported by WHO endorsements for its 60% risk reduction in heterosexual transmission. Access disparities persist due to regulatory hurdles and intellectual property constraints, with only 37 countries reporting significant PrEP initiations by late 2024 under UNAIDS monitoring, despite global scale-up goals. Policies in high-income settings, such as U.S. Medicaid expansions, have boosted PrEP uptake, but low-resource areas face supply chain issues and user fees, prompting calls for generic approvals and task-shifting to non-physicians. Empirical analyses indicate that enabling legal environments—such as those prohibiting discrimination in healthcare—correlate with higher prevention service utilization, though implementation lags in regions with conservative statutes. Overall, frameworks prioritizing empirical outcomes over punitive measures have demonstrated greater success in reducing incidence, as evidenced by PEPFAR's pre-2025 impacts.

Screening, Testing, and Follow-Up Protocols

Screening for HIV infection targets individuals based on age and risk factors to enable early detection and intervention, thereby reducing transmission through prompt treatment. The U.S. Centers for Disease Control and Prevention (CDC) recommends that all persons aged 13 to 64 years undergo at least one HIV test as part of routine health care, with recent draft guidelines proposing a shift to at least one test for those aged 15 years and older, eliminating an upper age limit and emphasizing risk-based screening for younger adolescents and older adults. High-risk groups, including men who have sex with men (MSM), persons who inject drugs, individuals with multiple sexual partners, those with sexually transmitted infections, and recipients of blood products, warrant annual or more frequent testing, such as every 3 to 6 months depending on exposure levels. Pregnant individuals should receive routine screening, ideally in the first trimester, with repeat testing in the third trimester for those at continued risk. The World Health Organization (WHO) endorses a public health approach to HIV testing services, prioritizing index testing (partner notification) and self-testing to expand reach, particularly in high-prevalence settings. HIV testing employs a multi-step algorithm to balance sensitivity, specificity, and diagnostic accuracy. Initial screening typically uses fourth-generation antigen/antibody (Ag/Ab) combination immunoassays, which detect both HIV-1/2 antibodies and p24 antigen, achieving >99% sensitivity and specificity. These tests have a window period of 18 to 45 days post-exposure, detecting infection in 50% of cases by 18 days and 99% by 44 days. Positive results prompt confirmatory testing: HIV-1/2 differentiation immunoassays followed by nucleic acid amplification tests (NAAT) or HIV RNA assays if indeterminate, with NAAT offering the shortest window (10-33 days) but reserved for acute suspicion due to cost. Rapid point-of-care tests, including self-tests, provide results in 20-30 minutes with similar accuracy but require follow-up confirmation for positives. Antibody-only tests (third-generation) extend the window to 23-90 days and are less preferred.
Test TypeDetection TargetsWindow Period (Median/99%)Sensitivity/Specificity
Fourth-Generation Ag/Abp24 Ag + HIV-1/2 Ab18-45 days>99% / >99%
Antibody-Only (3rd Gen)HIV-1/2 Ab23-90 days>99% / >99%
NAAT (RNA/DNA)HIV RNA/DNA10-33 days>99% / >99%
Follow-up protocols for positive diagnoses prioritize rapid antiretroviral therapy (ART) initiation to achieve viral suppression and prevent transmission. Upon confirmation, baseline assessments include CD4 count, HIV RNA viral load, genotypic resistance testing, hepatitis B/C serology, and HLA-B*5701 screening if abacavir is considered; ART should begin the same day if labs are pending and no contraindications exist, per CDC and WHO rapid initiation guidelines updated in 2023-2024. Viral load monitoring occurs at 4-8 weeks post-initiation, then quarterly until undetectable (<200 copies/mL), with adherence counseling and partner notification services to trace and test contacts. For initial negatives, high-risk individuals require retesting every 3-6 months, while low-risk persons may retest every 3-5 years. These protocols, grounded in empirical data showing 96% transmission reduction with undetectable viral loads, underscore testing's causal role in prevention.

Historical Evolution

1980s: Initial Response and Awareness

The first cases of what would later be identified as AIDS were reported by the Centers for Disease Control and Prevention (CDC) on June 5, 1981, describing five instances of Pneumocystis carinii pneumonia among previously healthy homosexual men in Los Angeles, marking the onset of systematic surveillance to track the emerging syndrome. This surveillance, initiated without delay, enabled early characterization of risk factors, including male-to-male sexual contact and intravenous drug use, informing initial prevention guidance focused on reducing exposure through behavioral modifications such as avoiding shared needles and limiting high-risk sexual practices. By 1982, the CDC expanded case reporting requirements nationwide, establishing AIDS as a reportable condition to monitor incidence and transmission patterns empirically. In March 1983, the U.S. Public Health Service issued its first formal recommendations for AIDS prevention, advising deferral of blood donations from high-risk groups and emphasizing infection control in healthcare settings, based on observed transmission via blood products among hemophiliacs and transfusion recipients. These measures preceded the identification of HIV as the causative agent in 1983-1984, relying on epidemiological data to advocate causal risk reduction without effective diagnostics or treatments available. The CDC established a National AIDS Hotline in 1983 to disseminate information on transmission risks, handling inquiries that underscored public confusion and the need for clear, evidence-based messaging. A pivotal advancement in prevention occurred in March 1985, when the FDA licensed the first commercial HIV antibody screening test, leading to immediate implementation in U.S. blood banks and a sharp decline in transfusion-related transmissions from prior rates of approximately 1 in 100 units contaminated. In 1986, Surgeon General C. Everett Koop released a report urging comprehensive sex education in schools, promotion of condom use, and monogamy to mitigate sexual transmission, countering political reluctance with data-driven calls for widespread awareness despite opposition from conservative factions. This was followed in 1987 by the CDC's America Responds to AIDS campaign, the first national multimedia effort to boost public understanding of HIV risks and prevention, targeting behaviors empirically linked to outbreaks in affected communities. Internationally, the World Health Organization launched its Global Programme on AIDS in 1987, coordinating early global surveillance and risk education in response to spreading cases beyond initial U.S. and European clusters. These initiatives, though hampered by stigma and underfunding—evident in the U.S. federal response's initial minimalism—laid foundational empirical strategies for prevention centered on transmission causality rather than unsubstantiated optimism.

1990s-2000s: Shift to Antiretrovirals and Global Scaling

The introduction of highly active antiretroviral therapy (HAART) in the mid-1990s represented a fundamental shift in HIV management, transitioning from single-drug regimens like zidovudine (AZT), approved in 1987, to combination therapies that suppressed viral replication more effectively. By 1996, HAART regimens, typically involving three or more drugs from at least two classes, became standard in high-resource settings, leading to a 47% decline in U.S. AIDS-related deaths by 1997 and substantial reductions in viral loads among treated individuals. This suppression decreased infectiousness, providing an empirical basis for integrating treatment into prevention strategies, though widespread recognition of treatment as prevention emerged later. Antiretroviral interventions specifically targeted mother-to-child transmission (MTCT) during this era, with the Pediatric AIDS Clinical Trials Group (PACTG) 076 trial in 1994 demonstrating that a zidovudine regimen administered to HIV-positive pregnant women and their newborns reduced MTCT risk by approximately two-thirds, from 25.5% to 8.3% in non-breastfeeding populations. In resource-limited settings, the HIVNET 012 trial in Uganda, published in 1999, showed that a single oral dose of nevirapine to mothers at delivery and to infants within 72 hours reduced MTCT by 50% compared to short-course zidovudine, offering a more affordable option at about $4 per course. Post-exposure prophylaxis (PEP) also advanced, with U.S. Public Health Service guidelines in 1996 recommending combination antiretrovirals for occupational exposures following needlestick injuries, and extension to non-occupational exposures like sexual assault or high-risk encounters formalized in 1998 guidelines, estimating up to 81% risk reduction based on animal models and early human data. The 2000s saw global scaling of these biomedical approaches through multilateral initiatives, beginning with the establishment of the Joint United Nations Programme on HIV/AIDS (UNAIDS) in 1996, which coordinated prevention efforts across UN agencies and emphasized ARV access in low-income countries. The Global Fund to Fight AIDS, Tuberculosis and Malaria, launched in 2002, invested over $27 billion by 2025 in HIV programs, including ARV provision that supported PMTCT scaling and averted millions of pediatric infections. Complementing this, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), enacted in 2003 with initial funding of $15 billion over five years, rapidly expanded ARV treatment to over 1.2 million people by 2008, prioritizing PMTCT and PEP in 15 focus countries, primarily in sub-Saharan Africa, where MTCT rates dropped significantly due to increased testing and drug distribution. These efforts integrated ARVs with behavioral prevention, such as voluntary counseling and testing, but faced challenges in adherence and supply chains in high-burden regions.

2010s-2025: PrEP Expansion and Recent Biomedical Advances

In the early 2010s, pre-exposure prophylaxis (PrEP) emerged as a biomedical strategy for HIV prevention, involving the daily oral administration of antiretroviral drugs to high-risk individuals prior to potential exposure. The U.S. Food and Drug Administration (FDA) approved tenofovir disoproxil fumarate-emtricitabine (Truvada) for PrEP on July 16, 2012, based on clinical trials demonstrating up to 99% reduction in HIV acquisition risk among adherent users engaging in sexual activity. This approval marked a shift from reliance on behavioral interventions, enabling pharmacological prevention for populations such as men who have sex with men (MSM) and serodiscordant couples, though real-world efficacy was tempered by adherence challenges, with studies showing protection dropping below 90% in non-adherent users. The World Health Organization (WHO) endorsed oral PrEP in 2015, recommending tenofovir-based regimens for individuals at substantial HIV risk, which spurred global implementation guidelines and integration into national programs. By the late 2010s, PrEP uptake expanded significantly in high-income countries; for instance, U.S. prescriptions rose from approximately 3,000 users in 2012 to over 200,000 by 2019, correlating with declines in new HIV diagnoses among targeted groups, though coverage remained below 10% of at-risk individuals. In the 2020s, efforts like the U.S. Ending the HIV Epidemic initiative prioritized PrEP scale-up, aiming for 50% coverage among high-risk populations by emphasizing access in underserved areas. Globally, PrEP initiation grew, but disparities persisted, with low adoption in low-income regions due to cost and supply barriers. Biomedical innovations in the 2020s focused on long-acting formulations to address daily pill adherence issues, which undermine oral PrEP's potential. In 2019, the FDA approved tenofovir alafenamide-emtricitabine (Descovy) as an alternative oral PrEP option with reduced renal and bone side effects compared to Truvada. A major advance came with cabotegravir, an integrase inhibitor; the FDA approved extended-release injectable cabotegravir (Apretude) for PrEP on December 20, 2021, administered every two months after initial loading doses, with trials showing superior efficacy (66% relative risk reduction versus daily oral tenofovir) in cisgender women and comparable protection in MSM. By 2025, lenacapavir, a capsid inhibitor, represented the latest PrEP milestone, with FDA approval on June 18 for subcutaneous administration every six months (branded Yeztugo), based on PURPOSE 1 and 2 trials demonstrating zero HIV seroconversions in over 2,000 MSM and transgender participants, yielding 100% efficacy and favorable safety. These long-acting injectables offer discrete, adherence-independent options, potentially transforming prevention in resource-limited settings, though high costs (e.g., cabotegravir at $22,000 annually in the U.S.) and implementation logistics pose rollout challenges. WHO guidelines for lenacapavir were anticipated in mid-2025 to facilitate global access. Ongoing research into implants and vaginal rings continues, but injectables dominate recent advances, with projections estimating they could avert millions of infections if scaled equitably.

Controversies, Criticisms, and Empirical Critiques

Debates on Harm Reduction vs. Abstinence Promotion

Harm reduction strategies in HIV prevention accept the persistence of high-risk behaviors—such as unprotected sex or injection drug use—and seek to mitigate associated harms through interventions like condom promotion, pre-exposure prophylaxis (PrEP), and syringe services programs (SSPs). These approaches have empirical support in specific contexts; for instance, meta-analyses of SSPs indicate they reduce HIV transmission among people who inject drugs (PWID) by providing sterile needles, with one review of 12 studies finding consistent associations with lower HIV incidence, particularly when integrated with medication-assisted treatment. Similarly, randomized trials of PrEP demonstrate up to 92% efficacy in preventing HIV acquisition among men who have sex with men (MSM) when adherence is high, though real-world implementation often yields lower protection due to inconsistent use. Abstinence promotion, conversely, emphasizes behavioral modification to eliminate exposure risks, advocating delayed sexual debut among youth, sexual fidelity in partnerships, and abstinence from injection drug use. Uganda's ABC program (Abstinence, Be faithful, Condoms), implemented from the late 1980s, exemplifies this approach and is credited with reversing national HIV prevalence from an estimated 15% in 1990 to 5% by 2007, driven primarily by reductions in premarital sex and multiple partnerships rather than widespread condom uptake. Peer-reviewed analyses attribute the decline to cultural and religious campaigns fostering partner limitation, with HIV incidence falling sharply among 15-19-year-olds as median sexual debut age rose. Systematic reviews of abstinence-plus education (combining delay tactics with limited condom information) further show short- and long-term reductions in HIV risk behaviors among adolescents in high-income settings. Critics of harm reduction contend it may foster risk compensation, where interventions like PrEP or condoms lead to increased sexual risk-taking, offsetting preventive gains; observational studies report rises in bacterial sexually transmitted infections (STIs) among PrEP users, with one analysis linking PrEP initiation to behavioral disinhibition in subgroups of MSM, though HIV incidence remains suppressed due to pharmacologic protection. In Uganda, HIV declines stalled in the mid-2000s after international donors shifted emphasis toward condom-centric harm reduction, correlating with resumed increases in early sexual activity. Proponents argue abstinence-based methods achieve causal risk elimination via first-principles—preventing exposure prevents transmission—outperforming probabilistic harm reduction in resource-limited settings where adherence falters, as evidenced by sustained low transmission in fidelity-focused communities. Direct comparative trials are scarce, but available evidence favors integrated approaches prioritizing behavior change; a review notes stronger empirical backing for abstinence-oriented interventions in altering root causes like partner concurrency, while harm reduction excels in acute mitigation for entrenched users but risks moral hazard without addressing addiction or promiscuity drivers. Public health bodies like UNAIDS advocate harm reduction as pragmatic, yet analyses highlight potential biases in such endorsements, stemming from institutional preferences for non-judgmental frameworks over culturally tailored abstinence messaging that proved effective in Uganda. Ongoing debates underscore the need for context-specific evaluation, with abstinence promotion showing superior long-term prevalence reductions in populations responsive to normative shifts.

PrEP Adherence, Costs, and Risk Compensation

Adherence to pre-exposure prophylaxis (PrEP) regimens, typically involving daily oral tenofovir disoproxil fumarate-emtricitabine (TDF/FTC), is critical for efficacy, with studies demonstrating near-100% protection against HIV acquisition when adherence exceeds 80% as measured by plasma tenofovir levels. Real-world adherence rates vary, with approximately 85% of users adherent after three months but dropping to over 50% after one year in U.S. commercial claims data from 2018–2020. Factors influencing poor adherence include stigma, side effects such as gastrointestinal issues, and forgetfulness, with systematic reviews reporting overall adherence ranging from 50% to 80% across diverse populations. Interventions like long-acting injectables, such as cabotegravir approved in 2021, aim to address oral adherence challenges by requiring dosing every two months, though real-world data on sustained use remains limited as of 2025. Costs of PrEP represent a significant barrier to widespread implementation, particularly in low-resource settings. Brand-name TDF/FTC (Truvada) lists at approximately $22,000 annually in the U.S., though generics introduced post-2020 patent expiration have reduced average total care costs by 56.7% between 2018 and 2022, from $127,529 to $55,179 per patient-year in insured populations. Long-acting options like lenacapavir, showing 96–100% efficacy in trials, carry brand prices exceeding $39,000 yearly, but generic manufacturing estimates suggest production costs as low as $25–$40 per patient-year at scale in low- and middle-income countries. Injectable cabotegravir-based PrEP, approved in 2025 for broader use, is priced at $28,000 annually in the U.S., limiting access despite potential adherence benefits. These disparities highlight how pharmaceutical pricing, rather than production costs, constrains global equity, with peer-reviewed analyses emphasizing the need for voluntary licensing to generics for cost-effective scaling. Risk compensation, the hypothesis that perceived protection from PrEP leads to increased high-risk behaviors such as condomless sex, has been debated in HIV prevention literature. Early randomized trials, including those reviewed by the USPSTF in 2019, found no significant evidence of behavioral risk elevation among PrEP users compared to placebo arms. However, observational data post-implementation reveal rising sexually transmitted infection (STI) rates among PrEP users, with some studies attributing this to reduced condom use; for instance, a 2019 review noted increased STIs potentially linked to compensation, challenging claims of negligible effects. Mathematical models indicate that even modest compensation could amplify transmission of drug-resistant HIV strains, underscoring causal risks beyond initial trial settings. A 2024 Danish cohort study comparing pre- and post-PrEP STI incidence found no overall increase but highlighted subgroup variations, suggesting compensation may manifest selectively rather than uniformly, with empirical critiques emphasizing the need for ongoing monitoring over assumptions of behavioral neutrality.

Ethical Issues in Trials and Policy Implementation

Ethical challenges in HIV prevention trials often center on informed consent, particularly in resource-limited settings with low literacy rates and cultural barriers. Participants in HIV vaccine trials, for instance, frequently exhibit incomplete comprehension of trial procedures, risks such as potential vaccine-induced seropositivity leading to stigma, and the experimental nature of interventions, complicating true voluntariness. In sub-Saharan African contexts, informed consent processes for prevention studies have been criticized for inadequate adaptation to local languages and customs, raising doubts about whether participants fully grasp long-term implications like discrimination or access to follow-up care. The use of placebo controls in trials for biomedical preventives like PrEP or microbicides has sparked debate over equipoise, especially when partially effective standards of prevention exist. Guidelines permit placebos only if added to proven interventions, but critics argue this undermines scientific rigor or exposes participants to undue risk in high-prevalence areas; for example, early PrEP trials navigated this by providing comprehensive counseling, yet ethical lapses in monitoring risk compensation behaviors persisted. Male circumcision trials in Africa, such as those in Orange Farm (2005) and Rakai (2007), faced accusations of methodological flaws and ethical oversights, including randomization despite prior observational evidence of benefit, potential coercion through incentives, and insufficient post-trial infrastructure for scaling, which some viewed as exploiting vulnerable populations without assured community benefits. In policy implementation, disparities arise from unequal post-trial access and potential exploitation in developing countries, where trials often occur without commitments to affordable intervention rollout, as seen in historical critiques of vertical transmission prevention studies denying proven regimens to controls. Community engagement remains inconsistent, with policies like voluntary medical male circumcision programs in Africa (initiated post-2007 trials) raising concerns over cultural imposition, replacement of traditional practices, and measurement biases favoring efficacy claims despite real-world adherence failures. Moreover, implementing harm reduction policies, such as needle exchanges, involves balancing public health imperatives against enabling illegal behaviors, with ethical tensions amplified in settings where abstinence promotion competes but lacks empirical prioritization in biased institutional frameworks.

Global Challenges and Future Outlook

Disparities in Access and Outcomes

Sub-Saharan Africa accounts for approximately 65% of global HIV infections and 70% of new cases in 2024, despite comprising only 15% of the world's population, highlighting stark regional disparities driven by limited access to prevention tools like PrEP and condoms in low-resource settings. In contrast, high-income regions such as Western Europe and North America report new infection rates below 0.1% of the population annually, benefiting from widespread availability of antiretrovirals for prevention and routine testing. These gaps persist due to infrastructural barriers, including insufficient healthcare facilities and supply chain issues for biomedical interventions, with only 15% of people in low- and middle-income countries outside sub-Saharan Africa accessing PrEP in 2023, compared to over 50% eligibility coverage in high-income nations. Within countries, racial and ethnic disparities exacerbate uneven prevention outcomes; in the United States, Black/African Americans and Hispanics/Latinos accounted for over 70% of new HIV diagnoses in 2022, despite representing 40% of the population, linked to lower PrEP uptake rates—Black men who have sex with men (MSM) access PrEP at rates 50% below white MSM counterparts due to systemic barriers like mistrust in healthcare and geographic maldistribution of services. Women face compounded challenges, with Black women comprising 54% of female HIV diagnoses in 2021 while making up less than 15% of the female population, attributable to heterosexual transmission risks amplified by partner serodiscordance and limited female-initiated prevention options beyond condoms. Globally, key populations such as MSM, sex workers, and transgender individuals experience infection rates 10-20 times higher than the general population, yet at least 50% remain unreached by tailored prevention services due to stigma and criminalization in many jurisdictions. Socioeconomic factors further widen these divides: rural residents report 20-30% lower PrEP adherence and testing rates than urban dwellers, stemming from transportation barriers and fewer providers, as evidenced in U.S. analyses showing rural areas with poverty rates above 20% having HIV incidence 1.5 times urban averages. In PEPFAR-supported countries, PrEP-to-need ratios vary threefold by subregion, with Eastern and Southern Africa achieving higher coverage (up to 40% of high-risk adults) than Asia or Latin America (under 10%), reflecting funding prioritization and local implementation efficacy. Youth under 25, particularly in low-income settings, show the slowest progress, with new infections stable at 300,000 annually since 2010, tied to inadequate school-based education and parental consent requirements hindering access. These patterns underscore that while biomedical advances like PrEP reduce incidence by up to 90% in adherent high-access groups, unaddressed social determinants perpetuate higher transmission in marginalized cohorts.

Integration with Broader Health Strategies

Integration of HIV prevention into primary health care systems has been shown to enhance overall health service delivery and sustain gains against the epidemic. A systematic review of 34 studies indicated that such integration improves patient retention in HIV care by up to 20% in some settings and increases uptake of preventive services like testing and counseling when bundled with routine primary care visits. This approach leverages existing infrastructure, reducing duplication of efforts and costs; for instance, combining HIV screening with tuberculosis diagnostics in high-burden areas has yielded efficiencies of 15-30% in resource use, according to modeling from integrated programs in sub-Saharan Africa.00156-0/fulltext) However, evidence quality varies, with many studies relying on observational data rather than randomized trials, necessitating cautious interpretation of causal impacts. Synergies with sexual and reproductive health (SRH) services represent a key pillar, where HIV prevention is embedded alongside family planning and maternal care to address overlapping risk factors. Integration efforts have boosted adolescent service uptake by nearly 20%, with programs in Southern Africa demonstrating higher condom distribution and PrEP initiation rates when co-located with SRH clinics. The U.S. Centers for Disease Control and Prevention's Program Collaboration and Service Integration (PCSI) framework exemplifies this domestically, coordinating HIV efforts with sexually transmitted infection and viral hepatitis control, resulting in improved case detection and reduced transmission clusters through shared surveillance systems as of 2024 updates. Globally, embedding HIV interventions within universal health coverage (UHC) schemes has expanded access, as seen in Indonesia where UHC enrollment doubled HIV treatment claims from 2012 to later years, though funding shifts toward domestic sources highlight risks of under-prioritization without sustained political commitment.30704-5/fulltext) Broader alignments with non-communicable disease management and poverty alleviation programs further amplify prevention impacts. Evidence from multi-country analyses shows that linking HIV services to chronic care models improves viral suppression rates by 10-15% via shared adherence support mechanisms. Collaborative strategies in Africa, integrating HIV with reproductive health and socioeconomic interventions, have reduced incidence by addressing upstream determinants like gender inequality, though empirical critiques note that integration success depends on robust health system capacity, with weaker systems experiencing service fragmentation rather than true synergies. As of 2025, frameworks like UNAIDS' Prevention 2025 Roadmap advocate tailored, population-specific bundling to align with UHC goals, emphasizing evidence-based combinations over siloed approaches to avoid inefficiencies.

Projections and Unmet Needs Based on 2025 Data

In 2024, an estimated 1.3 million [1.0–1.7 million] people acquired HIV globally, representing a 40% decline since 2010 but falling short of the 2025 target of fewer than 370,000 new infections. AIDS-related deaths totaled 630,000 [490,000–820,000], a 54% reduction from 2010 levels, while the number of people living with HIV reached 40.8 million [37.0–45.6 million]. Projections indicate that without accelerated interventions, new infections and deaths will not meet UNAIDS 2030 goals of a 90% reduction from 2010 baselines, potentially peaking prevalence at around 40 million before a slow decline as deaths outpace new cases.01449-7/fulltext) A permanent cessation of key funding, such as the U.S. PEPFAR program's $4.3 billion reduction in 2025, could lead to 6 million additional infections and 4 million extra AIDS deaths by 2030, exacerbating supply chain disruptions and service suspensions in low- and middle-income countries. Unmet prevention needs remain substantial, with pre-exposure prophylaxis (PrEP) reaching only 3.9 million people in 2024 against a 2025 target of 21.2 million, particularly among key populations like men who have sex with men, sex workers, and transgender individuals, where fewer than 50% receive tailored services. In sub-Saharan Africa, which accounts for 60% of people living with HIV, adolescent girls and young women (aged 15–24) saw 210,000 new infections in 2024 despite a 56% regional decline since 2010, highlighting gaps in targeted biomedical and behavioral interventions. Among children, 120,000 [82,000–170,000] new infections occurred via vertical transmission, with 620,000 of 1.4 million [1.1–1.8 million] children living with HIV untreated, underscoring failures in elimination efforts. Progress toward the 95-95-95 targets (diagnosis, treatment, viral suppression) stood at 87% diagnosed, 89% of diagnosed on antiretroviral therapy, and 94% suppressed in 2024, but 9.2 million people living with HIV—half in sub-Saharan Africa—remain untreated. Funding disruptions since early 2025 have halted programs in over 60% of surveyed women-led HIV organizations, with external aid comprising 80% of prevention financing in sub-Saharan Africa, revealing dependency vulnerabilities and the need for domestic resource mobilization in 25 low- and middle-income countries planning increases by 2026. Rising infections in Eastern Europe/Central Asia (94% increase since 2010) and the Middle East/North Africa (7% increase) further emphasize unmet needs for adapted strategies beyond sub-Saharan focus.

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