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Preventing HIV in women in Africa. HIV incidence is declining globally, but around half of all new infections are in sub-Saharan Africa-where adolescent girls and young women bear a disproportionate burden of new infections. Those who sell sex are at particularly high risk. Despite declining incidence rates and availability of effective biomedical prevention tools, we are not on track, globally or in Africa, to achieve UNAIDS 2025 prevention targets. For those at risk, interventions that strengthen their motivation, capabilities and access to all available HIV prevention technologies are critical-for adolescent girls and women in particular, but also for epidemic control more broadly. Exciting possibilities for scaling up new and highly effective prevention technologies are close, but delivery, implementation and financing models need to be developed and urgently evaluated, in partnership with communities, or these opportunities may be lost. Here, we discuss the evolving landscape of biomedical prevention technologies for women in Africa, their implementation and financing, as well as priorities for HIV prevention research in this setting.

UNAIDS estimates that 25% of all new infections that occurred across SSA in 2022 were among key populations and their sexual partners6,16. UNAIDS defines key populations as those people who are at higher risk of HIV and other health issues due to their behaviors; this includes female sex workers17,18. HIV incidence among female sex workers is nine times higher than among all women, with this difference over 20 times greater in western and Central Africa and five times greater in eastern and southern Africa19. Young women who sell sex are especially vulnerable, because they experience relationship power imbalances due to their age as well as their gender. All women who sell sex do so against a background of intense stigma and discrimination, exacerbated by criminalization of sex work20. These challenges are likely to increase as a result of the recent erosion of sexual and reproductive rights in parts of Africa, the impact of climate change and the rise in conflicts, all of which negatively affect engagement with prevention services10. As HIV epidemics become better controlled across the continent, the relative importance of these ‘key’ populations is likely to increase. In this scenario, failure to keep sex workers healthy could result in in repeated outbreaks of HIV as a result of direct or indirect transmission through sex work21. Modeling suggests that increasing the intensity of HIV prevention programs for female sex workers in SSA would offer cost-effective and beneficial impacts on population incidence22.

o keep sex workers healthy could result in in repeated outbreaks of HIV as a result of direct or indirect transmission through sex work21. Modeling suggests that increasing the intensity of HIV prevention programs for female sex workers in SSA would offer cost-effective and beneficial impacts on population incidence22. On the other hand, half of all new infections in SSA are in the general population, and while many of the risk factors for incident infection are known (for example, place of residence, young age, STIs, non-cohabiting with sex partners, selling sex, violence), general population prevention services have struggled to reach those at highest risk who are not easily identifiable23,24. Importantly, not all adolescent girls and women are equally at risk. In an analysis of population-representative surveys conducted across Africa between 1985 and 2020, the proportion of women reporting ever having sex before age 18 varied by region from under 25% to over 77% (highest in West and Central Africa) and the median age of sexual debut was above 18 in both eastern and southern Africa—the regions with highest rate of new infections (although there is considerable within-region variation)25. Without doubt, new approaches are required. Evidence from the Isisekelo Sempilo trial in rural South Africa showed that offering home-based sampling for STI testing and integrated sexual and reproductive health combined with HIV mobile services, increased uptake of HIV prevention by 60%26. Other models offer PrEP and family planning in the same facilities but from different providers27,28. However, these integrated models have not been scaled up for primary HIV prevention delivery in SSA29.

ated sexual and reproductive health combined with HIV mobile services, increased uptake of HIV prevention by 60%26. Other models offer PrEP and family planning in the same facilities but from different providers27,28. However, these integrated models have not been scaled up for primary HIV prevention delivery in SSA29. Some of those at highest risk are likely individuals who sell sex but do not identify as sex workers (Fig. 1). A review from the mid-2000s found that when women in Africa were asked (in demographic and health surveys) about exchanging sex for gifts or money in the past 12 months, roughly twice as many women responded affirmatively compared to the number reporting being sex workers30. In Zimbabwe, young women who report selling sex but do not identify as sex workers tend to have fewer sex partners than those who do identify as sex workers, but their rate of HIV acquisition is just as high31. Similarly, in rural KwaZulu-Natal, South Africa, incidence of HIV infections among young women who sell sex (17% of young women overall) was 8% per annum, three times that of young women who did not report selling sex32. A comprehensive review of over 300 social science studies exploring transactional sex in SSA observed three overlapping motivations; sex for basic needs, sex for improved social status and sex and material expression of love. Crucially, the associated risks and appropriate mitigation approaches differ between these33.

A comprehensive review of over 300 social science studies exploring transactional sex in SSA observed three overlapping motivations; sex for basic needs, sex for improved social status and sex and material expression of love. Crucially, the associated risks and appropriate mitigation approaches differ between these33. Expanding tailored services for key populations—for example, by introducing peer-led social and sexual network approaches—may reach this population of women who transact sex but who, as a group, are less well characterized than self-identifying female sex workers. By contrast, most current strategies seek to identify and reach high-risk individuals from within ‘general population’ platforms (which include many people at very low or no risk). We argue that research to explore the relative merits (and cost-effectiveness) of both these approaches is needed. In addition, working cooperatively with these groups of women may help researchers to better understand who needs which services and where, and to identify optimal ways to package services, such as STI testing and sexual and reproductive health.

lative merits (and cost-effectiveness) of both these approaches is needed. In addition, working cooperatively with these groups of women may help researchers to better understand who needs which services and where, and to identify optimal ways to package services, such as STI testing and sexual and reproductive health. Other populations with high rates of HIV acquisition in SSA include tertiary education students, who report condomless sex, multiple partnerships, transactional sex and sex while intoxicated34,35. Pregnant and lactating adolescent girls and young women are another group with high HIV incidence, with new HIV infections associated with higher rates of mother-to-child transmission than preexisting HIV infections36. This group is relatively easy to identify and access through maternal and child health clinics. Although PrEP is recommended for this population37, and research shows its provision to be feasible and safe38, PrEP has not been adequately integrated into antenatal care39–41.

PrEP and PEP agents have been rolled out to varying degrees (and with varying levels of success) in African countries, while recent advances in drug development are generating longer-lasting and more-effective options. In practice, however, prevention choices for women in Africa are often limited to condoms and daily oral PrEP. Below, we discuss the effectiveness, cost-effectiveness and availability of PrEP and PEP options for women in Africa. Other strategies such as preventive vaccines and broadly neutralizing antibodies are also being developed and tested, but these are not currently in a position to have real-world impact, so they are not discussed here.

s the effectiveness, cost-effectiveness and availability of PrEP and PEP options for women in Africa. Other strategies such as preventive vaccines and broadly neutralizing antibodies are also being developed and tested, but these are not currently in a position to have real-world impact, so they are not discussed here. Since 2015, the World Health Organization (WHO) has recommended daily oral PrEP42 for people at substantial risk of HIV (defined as HIV incidence greater than 3% per annum in their population group). More recently, longer-acting PrEP options—such as the monthly dapivirine vaginal ring (DVR) and injectable long-acting cabotegravir (CAB-LA; administered every 2 months)43–46—have been recommended and pre-qualified by the WHO, and are being scaled up to varying extents across Africa. Globally, 76 countries have national PrEP guidelines in place, with the global oral PrEP target set at 10 million individuals initiated by 2025. As of July 2024, only 7.5 million people had initiated oral PrEP globally47. According to the Global PrEP Tracker (https://data.prepwatch.org/), scale-up in Africa started in 2016 and by mid-2024, 3.7 million people in eastern and southern Africa and 706,000 in western and Central Africa had started oral PrEP. In South Africa, where more than 5.25 million people are eligible, only 1.35 million (<26%) had received a prescription by June 2024; effective use is likely lower48. PrEP rollout is crucial to achieving targets for HIV prevention, but unless careful consideration is given to implementation, for example, through service integration and task shifting, PrEP rollout could overburden already weak health systems49.

ad received a prescription by June 2024; effective use is likely lower48. PrEP rollout is crucial to achieving targets for HIV prevention, but unless careful consideration is given to implementation, for example, through service integration and task shifting, PrEP rollout could overburden already weak health systems49. Qualitative and quantitative data suggest a number of barriers to oral PrEP uptake and effective continuation50,51 (Box 2). Even among self-reported PrEP users, biomarkers often show low rates of actual protection—for example, among a sample of adolescent girls and young women who were regular PrEP program attendees in Kenya, fewer than 5% had protective plasma levels of tenofovir disoproxil fumarate (TDF; daily regimen). And among 578 female sex workers in Zimbabwe who reported current PrEP use in an end-of-trial survey (the AMETHIST trial), only 2 had TDF levels indicative of adherence at four or more doses per week52–54 (Fig. 2). There is some evidence that discussing TDF levels with users can reinforce adherence. The randomized, controlled HPTN 082 trial did not show any impact of this approach, although it had only modest power to detect such differences55; while the INSIGHT cohort56, an uncontrolled study that recruited over 3,000 adolescent girls and young women from several countries in Africa, showed high oral PrEP uptake (>95%) and continuation (>85% at 6 months) with this kind of communication. In this study, two-thirds of those tested at 6 months had detectable TDF; self-reported adherence aligned very well with positive results from the TDF test (in this case, a urine test) and over half the girls interviewed at 6 months reported that their urine TDF test result motivated them to take PrEP.

f communication. In this study, two-thirds of those tested at 6 months had detectable TDF; self-reported adherence aligned very well with positive results from the TDF test (in this case, a urine test) and over half the girls interviewed at 6 months reported that their urine TDF test result motivated them to take PrEP. The DVR offers an alternative strategy—a female-controlled HIV prevention method for women who do not want to take tablets or have injections. It consists of a flexible silicone ring that is inserted in the vagina and slowly releases the antiviral dapivirine over the course of one month. Very little drug is absorbed systemically. In trials, the ring reduced risk of HIV acquisition by 35%, or as much as 45% with optimal adherence45,46. It has been conditionally recommended by the WHO since 2021 but is currently only licensed for use in a few African countries, and is not available outside implementation studies. A 3-month vaginal ring is currently being evaluated. Aphase 1 trial (https://popcouncil.org/project/the-three-month-dapivirine-vaginal-ring-for-hiv-prevention/) to investigate the relative bioavailability of dapivirine with the monthly versus 3-monthly DVR found that the latter delivers dapivirine at higher levels than the former.

ginal ring is currently being evaluated. Aphase 1 trial (https://popcouncil.org/project/the-three-month-dapivirine-vaginal-ring-for-hiv-prevention/) to investigate the relative bioavailability of dapivirine with the monthly versus 3-monthly DVR found that the latter delivers dapivirine at higher levels than the former. Injectable PrEP is another long-lasting option that negates the need for taking pills daily. It is highly effective and widely preferred (over daily PrEP) in values and preferences studies57. In 2021 and 2022, large trials of injectable CAB-LA (given every 2 months) demonstrated its superiority compared to daily oral TDF in both men43 and women44. Recent safety data from HPTN084 suggest CAB-LA use is safe also in pregnant and lactating women58. Since 2022, the WHO has recommended that CAB-LA be offered as an additional prevention choice to those at substantial risk of HIV infection. CAB-LA is licensed for prevention in 53 countries worldwide and is starting to be rolled out in 11 countries in Africa48. However, supplies are limited and CAB-LA is not available to all who would choose it. So far, 15,000 people globally—but <3,000 African women—have been started on CAB-LA48.

al risk of HIV infection. CAB-LA is licensed for prevention in 53 countries worldwide and is starting to be rolled out in 11 countries in Africa48. However, supplies are limited and CAB-LA is not available to all who would choose it. So far, 15,000 people globally—but <3,000 African women—have been started on CAB-LA48. An important implication of CAB-LA scale-up is that infections occurring just before CAB-LA initiation (not detectable at the time of treatment initiation) or while taking CAB-LA are difficult to detect using standard testing algorithms. This is due to altered (clinically silent) presentation of acute HIV infection in people taking CAB-LA, a phenomenon known as ‘long-acting early viral inhibition’. Delayed diagnosis is associated with resistance to certain antiretroviral drugs including dolutegravir, a critical part of first-line HIV therapy regimens in most countries in Africa59. Modeling the cost-effectiveness of CAB-LA in SSA while taking account of the risk of drug resistance suggests that CAB-LA has the potential to avert more deaths over 50 years than daily oral PrEP, and would be cost effective if delivered at the same cost as oral PrEP60. The cost-effectiveness of CAB-LA has also been studied in South Africa, which has a much higher gross domestic product per capita than most other countries in the region. CAB-LA was not found to be cost effective when targeted to those at substantial risk unless the price could be reduced60–62. One model of maximum cost at which CAB-LA would be similarly cost effective to oral PrEP (in South Africa) found a per-dose cost ranging from $9.05 to $14.47, which is considerably less than current costs. The extent to which models differ in their findings of PrEP cost-effectiveness relate to assumptions about the degree to which it is effectively used by individuals—mostly only during periods in which they are likely to have new condomless partners—which is uncertain60–62.

which is considerably less than current costs. The extent to which models differ in their findings of PrEP cost-effectiveness relate to assumptions about the degree to which it is effectively used by individuals—mostly only during periods in which they are likely to have new condomless partners—which is uncertain60–62. The injectable antiretroviral capsid inhibitor lenacapavir is an even longer-lasting PrEP option, requiring subcutaneous injection only every 6 months. The randomized component of a large phase 3 trial (PURPOSE 1) of lenacapavir in African women was stopped in mid-2024 following a preplanned interim analysis, because there were no incident HIV infections in the lenacapavir arm (follow-up of participants continues)—while incidence in two different daily oral PrEP arms was similar to background incidence63. This has generated excitement about the possibility of a highly effective, twice-yearly prevention technology soon becoming available. The randomized component of a second trial of lenacapavir for HIV prevention in cisgender men and trans women (PURPOSE 2) was also stopped in late 2024 again for preventing incident infections, and other trials in the USA (https://www.purposestudies.com/) are due to report in 2025, evaluating len-acapavir in women (PURPOSE 3) and injecting drug users (PURPOSE 4). One modeling study assessed the cost-effectiveness of lenacapavir for HIV prevention among individuals at substantial risk in western Kenya, Zimbabwe and South Africa64. The maximum price at which lenacapavir could be cost effective varied by setting and by the extent to which eligibility was extended beyond those at highest risk. Wider coverage is predicted to avert more infections but lenacapavir would have to be delivered at even lower costs to remain cost effective; lenacapavir rollout to 1.6–4.0% of the population would avert 12.3–18.0% of infections and could be implemented cost-effectively at a price per dose of $106.30 (South Africa), $21.10 (Zimbabwe) and $16.60 (western Kenya). The potential cost per dose of lenacapavir in low- and middle-income countries is not yet known, but below $40 is thought to be achievable. Researchers projecting the minimum lenacapavir pricing based on generic mass production and a Cost-Plus model found it could be manufactured in bulk for <US$100 per person per year65.

potential cost per dose of lenacapavir in low- and middle-income countries is not yet known, but below $40 is thought to be achievable. Researchers projecting the minimum lenacapavir pricing based on generic mass production and a Cost-Plus model found it could be manufactured in bulk for <US$100 per person per year65. There is some disquiet that, without coordinated rollout of CAB-LA and lenacapavir (as did happen for dolutegravir, the preferred first-line antiretroviral treatment) widespread scale-up will likely be delayed66. The Coalition to Accelerate Access to Long-Acting PrEP (https://avac.org/resource/coalition-to-accelerate-access-to-long-acting-prep/), which includes the WHO, Global Fund, the US President’s Emergency Plan For AIDS Relief (PEPFAR) and other donors/advocates, has developed a plan for accelerated introduction of CAB-LA—but this plan retains the developer (ViiV Healthcare) as sole supplier in the initial period. This is a lost opportunity that advocacy groups are working to address67,68. The developer of lenacapavir (Gilead Sciences) has issued licenses to six generic manufacturers ahead of regulatory approval but this has also led to concerns about access and affordability69.

ealthcare) as sole supplier in the initial period. This is a lost opportunity that advocacy groups are working to address67,68. The developer of lenacapavir (Gilead Sciences) has issued licenses to six generic manufacturers ahead of regulatory approval but this has also led to concerns about access and affordability69. HIV PEP as recommended by the WHO is a 28-day course of antiretroviral medication, consisting of tenofovir disoproxil–lamivudine–dolutegravir (TLD), taken within 72 h after potential exposure to HIV70,71. PEP works by halting viral replication and preventing persistent infection. There have been no randomized controlled trials assessing the efficacy of HIV PEP. Nonhuman primate studies suggest that PEP may reduce the risk of acquiring HIV by around 90%72, with the efficacy likely to be higher the earlier PEP is initiated after sexual exposure. Based on studies in macaques, even a single dose of prophylaxis with tenofovir alafenamide (TAF)/emtricitabine (FTC) and an integrase inhibitor (elvitegravir) before or after sex leads to over 90% protection, leading the authors to conclude it is a promising HIV prevention strategy71. Likewise, Bekerman et al.73 found that two doses of TAF/FTC plus the integrase inhibitor bictegravir initiated within 24 h of exposure provided over 80% protection, greater than the protection offered with TAF/FTC alone. These studies suggest that HIV PEP can reduce the risk of infection if taken quickly after exposure and for a long enough period. Animal studies suggest that 28 days of PEP may not be required to prevent infection; if PEP is started rapidly (for example, within a day at most), a much shorter course would likely be effective, although there are no data in humans to confirm this. Also of note, PEP has the potential to act as a ‘gateway’ to PrEP initiation74.

dies suggest that 28 days of PEP may not be required to prevent infection; if PEP is started rapidly (for example, within a day at most), a much shorter course would likely be effective, although there are no data in humans to confirm this. Also of note, PEP has the potential to act as a ‘gateway’ to PrEP initiation74. TLD is the first-line therapy for millions of people living with HIV across Africa and thus is widely available and considered safe. Although PEP has been recommended by the WHO for years, in practice it is not easily accessible. It requires a prescription and, in many settings, it is reserved for people who have experienced sexual assault or an occupational exposure. The WHO have recently revised their guidelines to emphasize the importance of expanding access to PEP to all who are potentially exposed to HIV, making it easily available in communities so it can be initiated rapidly after exposure70. Monitoring PEP use with HIV self-testing was also recommended47. Although there are no randomized controlled trials to confirm the impacts of this approach, its potential benefits are considered to outweigh potential harms.

Since 2015, the World Health Organization (WHO) has recommended daily oral PrEP42 for people at substantial risk of HIV (defined as HIV incidence greater than 3% per annum in their population group). More recently, longer-acting PrEP options—such as the monthly dapivirine vaginal ring (DVR) and injectable long-acting cabotegravir (CAB-LA; administered every 2 months)43–46—have been recommended and pre-qualified by the WHO, and are being scaled up to varying extents across Africa. Globally, 76 countries have national PrEP guidelines in place, with the global oral PrEP target set at 10 million individuals initiated by 2025. As of July 2024, only 7.5 million people had initiated oral PrEP globally47. According to the Global PrEP Tracker (https://data.prepwatch.org/), scale-up in Africa started in 2016 and by mid-2024, 3.7 million people in eastern and southern Africa and 706,000 in western and Central Africa had started oral PrEP. In South Africa, where more than 5.25 million people are eligible, only 1.35 million (<26%) had received a prescription by June 2024; effective use is likely lower48. PrEP rollout is crucial to achieving targets for HIV prevention, but unless careful consideration is given to implementation, for example, through service integration and task shifting, PrEP rollout could overburden already weak health systems49.

HIV PEP as recommended by the WHO is a 28-day course of antiretroviral medication, consisting of tenofovir disoproxil–lamivudine–dolutegravir (TLD), taken within 72 h after potential exposure to HIV70,71. PEP works by halting viral replication and preventing persistent infection. There have been no randomized controlled trials assessing the efficacy of HIV PEP. Nonhuman primate studies suggest that PEP may reduce the risk of acquiring HIV by around 90%72, with the efficacy likely to be higher the earlier PEP is initiated after sexual exposure. Based on studies in macaques, even a single dose of prophylaxis with tenofovir alafenamide (TAF)/emtricitabine (FTC) and an integrase inhibitor (elvitegravir) before or after sex leads to over 90% protection, leading the authors to conclude it is a promising HIV prevention strategy71. Likewise, Bekerman et al.73 found that two doses of TAF/FTC plus the integrase inhibitor bictegravir initiated within 24 h of exposure provided over 80% protection, greater than the protection offered with TAF/FTC alone. These studies suggest that HIV PEP can reduce the risk of infection if taken quickly after exposure and for a long enough period. Animal studies suggest that 28 days of PEP may not be required to prevent infection; if PEP is started rapidly (for example, within a day at most), a much shorter course would likely be effective, although there are no data in humans to confirm this. Also of note, PEP has the potential to act as a ‘gateway’ to PrEP initiation74.

The scale of the challenge posed by HIV to African health systems in the 2000s and 2010s was unprecedented, with life expectancies in many countries falling (for example, to age 45 in Malawi and 33 in Zimbabwe in 2002) and wider economies buckling under the strain of the epidemic. The global community coalesced to generate funding to address this challenge. In 2002, the Global Fund to Fight for AIDS, Tuberculosis and Malaria (GFATM; https://www.theglobalfund.org/en/) was established and, in 2003, PEPFAR (https://www.state.gov/pepfar/) was launched. Today, both institutions account for almost all HIV funding in low-income African countries with high HIV prevalence (for example, in Malawi, Zimbabwe and Mozambique), whereas domestic funding for HIV has increased substantially only in relatively wealthier countries (for example, South Africa and Botswana).

launched. Today, both institutions account for almost all HIV funding in low-income African countries with high HIV prevalence (for example, in Malawi, Zimbabwe and Mozambique), whereas domestic funding for HIV has increased substantially only in relatively wealthier countries (for example, South Africa and Botswana). The global response to HIV has been an outstanding success, as evidenced by the fall in HIV infections, but there are concerns that the exceptional levels of international funding for HIV may not be sustained into the future. This is a challenging issue, as global priorities shift toward new concerns such as climate change and pandemic preparedness. International funding for HIV has flatlined in recent years1,75, and it is widely expected to fall in future. There are hopes that the fall can be mitigated by increased domestic funding for HIV, but this will not replace donor funding in full because countries face a myriad of other health, social and economic challenges. If funding does fall, this is likely to have adverse implications for HIV prevention, unless domestic funding can fill the gap.

he fall can be mitigated by increased domestic funding for HIV, but this will not replace donor funding in full because countries face a myriad of other health, social and economic challenges. If funding does fall, this is likely to have adverse implications for HIV prevention, unless domestic funding can fill the gap. Several countries have experimented with innovative financing mechanisms, such as the use of taxes/levies and debt conversion instruments, to increase the availability of domestic funds for HIV services. The Zimbabwe National AIDS Trust was established in 2000 and receives revenues from a tax on formal sector employers and employees, with 10% of proceeds going to prevention76. Cote d’Ivoire and Cameroon have recently agreed schemes with creditors, through the GFATM’s Debt4Health Swap, for their debt burdens to be reduced with released funds being committed to national HIV responses77. Given the moral imperative for countries to provide antiretroviral therapy to citizens living with HIV for their rest of their lives, it has been recognized that HIV infections create a financial quasi-liability which is comparable in some African countries to management of their ratio of debt to gross domestic product78. In such a context, it makes sense for countries to target available funds to maximally reduce new HIV infections, especially among women and those at highest risk. To date, many of the most prominent HIV prevention programs that focus on women have been financed primarily using international funding.

omestic product78. In such a context, it makes sense for countries to target available funds to maximally reduce new HIV infections, especially among women and those at highest risk. To date, many of the most prominent HIV prevention programs that focus on women have been financed primarily using international funding. There are risks that future financing of HIV prevention services will, therefore, be inadequate unless domestic contributions substantially increase. This requires a combination of science and advocacy. Encouragingly, health leaders across Africa appear to recognize the challenge. For instance, African heads of state committed in 2019 to the African Leaders Meeting Investing in Health Declaration, aiming to increase domestic spending on health, especially to meet the challenges posed by HIV79. It is critical that HIV prevention continues to be bolstered, to both ease fiscal challenges and ensure population health improvement.

As described above, we have highly effective tools for preventing acquisition of HIV (all of which have been shown to be safe) and many of these should, by now, be well embedded in health systems. In reality, however, too few people are accessing prevention tools effectively. Randomized trials in East Africa have shown that offering individuals the choice of whichever biomedical prevention method best fits their needs (oral PrEP, long-acting injectable PrEP or condoms and PEP in the event of exposure) and the option to change their choice if their circumstances or preferences change, increases coverage of high-risk transmission events and results in substantially more people initiating primary prevention80,81.

best fits their needs (oral PrEP, long-acting injectable PrEP or condoms and PEP in the event of exposure) and the option to change their choice if their circumstances or preferences change, increases coverage of high-risk transmission events and results in substantially more people initiating primary prevention80,81. The challenge for new technologies, which include new drug delivery mechanisms, is that they be developed in ways that will reduce barriers to their ongoing use, such as by ensuring privacy and ease of use. Many barriers can be mitigated without new technologies, by using the ones we already have better. For example, many countries have been reluctant to adopt WHO’s recommendation to de-medicalize and monitor PrEP or PEP use via HIV self-tests. Similarly, task shifting of PrEP/PEP prescribing to community cadre, pharmacies and/or self-care has not been adequate. There is resistance among stakeholders to changing existing prescribing, delivery and monitoring practices and regulations. Although such regulations are in place to ensure population safety, they are often maintained by vested interests (for example, health-care professionals’ concerns about ‘losing control’ over certain aspects of care)82.

ng stakeholders to changing existing prescribing, delivery and monitoring practices and regulations. Although such regulations are in place to ensure population safety, they are often maintained by vested interests (for example, health-care professionals’ concerns about ‘losing control’ over certain aspects of care)82. One way to make PEP more widely available is to provide TLD (WHO-recommended PEP) in communities for anyone to access without prescription. This approach would need to be coupled with community education to promote PEP following condomless sex. Freely available TLD might end up being used either as PrEP by people wanting to prevent infection or as treatment by people living with HIV, allowing them to circumvent the need to go to a clinic (even though these would not be the intended uses). Phillips et al.83 modeled effectiveness and cost-effectiveness of this approach; assuming a high uptake of TLD, they projected a mean reduction in general population HIV incidence in eastern and southern Africa of 31% over 20 years. Nonprescription, community-based TLD was cost effective in 90% of scenarios and cost-saving (in terms of disability-adjusted life years) in 58% of scenarios. A range of implementation research projects are currently underway to make PEP more easily available including through pharmacies, vouchers, community cadres and ‘PEP in Pocket’, but none have yet tested removing all barriers to TLD access84,85.

t-saving (in terms of disability-adjusted life years) in 58% of scenarios. A range of implementation research projects are currently underway to make PEP more easily available including through pharmacies, vouchers, community cadres and ‘PEP in Pocket’, but none have yet tested removing all barriers to TLD access84,85. Multipurpose prevention technologies combining antiretrovirals and contraception are a promising intervention for women who want to prevent HIV and pregnancy simultaneously86. Although reported acceptability and adherence to a dual PrEP/contraceptive pill was high among adolescent girls and young women in Zimbabwe, mean adherence was too low for protection, which did not differ between the dual PrEP/contraceptive pill and taking two pills separately87. Ongoing studies investigating a co-formulated smaller pill may give a better picture of adherence and impact88. A 3-month combined dapivirine–levonorgestrel vaginal ring was well tolerated, with plasma and cervicovaginal levels that compared well with a dapivirine-only ring and other levonorgestrel contraceptives89. Other future approaches under development include a subdermal implant that can be refilled by transcutaneous injection for ultra-long-acting delivery of antiretrovirals for PrEP, as well as long-acting oral prevention90.

al levels that compared well with a dapivirine-only ring and other levonorgestrel contraceptives89. Other future approaches under development include a subdermal implant that can be refilled by transcutaneous injection for ultra-long-acting delivery of antiretrovirals for PrEP, as well as long-acting oral prevention90. A major challenge is to identify and test the population impact of scalable implementation strategies, to ensure effective use of available technologies while advocating for coordinated introduction of new innovations (see Box 3 for implementation priorities). Proactively engaging communities of women will increase understanding that HIV is genuinely preventable and worth preventing. In Mysore, India, for example, within the Ashodaya Samithi sex worker collective, sex workers designed and implemented PrEP rollout as an integral part of their broader sexual health and social support program. Importantly, sex workers living with HIV were at the heart of community mobilization for PrEP, and were able to discuss the value of remaining uninfected with sex workers who were HIV-negative. In stark contrast to the numerous other demonstration programs run over that period, over 90% of all potential PrEP users opted to initiate PrEP; 86% of those were retained after 16 months, of whom 87% had protective levels of PrEP91,92.

discuss the value of remaining uninfected with sex workers who were HIV-negative. In stark contrast to the numerous other demonstration programs run over that period, over 90% of all potential PrEP users opted to initiate PrEP; 86% of those were retained after 16 months, of whom 87% had protective levels of PrEP91,92. Separately, there has been concern about ‘risk compensation’ among those using biomedical prevention, whereby condom use is reduced and rates of STIs rise. Evidence for this is limited93 as levels of condomless sex and STIs are already high in Africa and the high levels of efficacy for HIV prevention outweigh the potential behavioral impact. PrEP services are an opportunity to provide sexual health promotion, STI testing and treatment to those at highest risk of HIV and STI acquisition.

The immediate challenge for prevention research is to determine how to deploy the highly effective prevention tools already available (or nearly available) to ensure effective coverage among women who are at a substantial risk of infection. Evaluation of new biomedical tools including preventive vaccines will of course be required in the longer term if the goal of eradicating HIV infection is to become a reality. To maximize the impact of available and emerging technologies in the near future, equal priority must be given to efficacy and implementation research. Below, we outline key considerations for research in both of these areas.

While the falling global incidence of HIV and growing availability of effective primary prevention tools is a cause for celebration, it has implications for research aimed at assessing the efficacy of new biomedical prevention tools. Falling incidence rates mean that trials need to recruit more people to demonstrate impact, and they must be large enough to detect benefit or equivalence compared to existing products, rather than placebo. An additional complication is that the effectiveness of oral PrEP—a likely comparator to new innovations—is highly dependent on adherence, making it difficult to estimate efficacy. All of this poses challenges to the use of traditional randomized clinical trials that require impractically large sample sizes and non-inferiority designs. A consensus group of academic researchers, regulators, pharmaceutical innovators and other stakeholders (the Forum HIV Prevention Trial Design Project) proposed estimating HIV incidence in people not on PrEP as an external counterfactual, measured using a recent infection testing algorithm—to which on-PrEP incidence in trial participants could then be compared94.

gulators, pharmaceutical innovators and other stakeholders (the Forum HIV Prevention Trial Design Project) proposed estimating HIV incidence in people not on PrEP as an external counterfactual, measured using a recent infection testing algorithm—to which on-PrEP incidence in trial participants could then be compared94. This approach was adopted by the recent PURPOSE 1 trial63, which tested the effectiveness of 6-monthly injectable lenacapavir and TAF by comparing prospectively measured HIV incidence for each investigational agent to background HIV incidence among all those screened to take part in the trial (a cross-sectional incidence cohort). HIV incidence in each drug arm was also compared to that in an active internal control group receiving daily oral TDF. This new approach not only demonstrated the efficacy of lenacapavir, but also confirmed the difficulty women have in taking daily oral PrEP (incidence in the oral PrEP arm matched that in the corss-sectional incidence cohort). Therefore, it is likely that this approach will be used to assess emerging antiretroviral-based products.

roach not only demonstrated the efficacy of lenacapavir, but also confirmed the difficulty women have in taking daily oral PrEP (incidence in the oral PrEP arm matched that in the corss-sectional incidence cohort). Therefore, it is likely that this approach will be used to assess emerging antiretroviral-based products. A similar approach could potentially be used to assess the efficacy of new vaccines or broadly neutralizing antibodies, although it is more likely that these trials will use a placebo arm but allow access to standard-of-care PrEP in all trial arms, for anyone who chooses it. Additionally, investigators might combine trial resources to determine efficacy of different agents simultaneously—as happened in the PrEPVacc study, which combined trials of HIV vaccines with a trial of a novel oral PrEP agent (TAF) in women95. Implementation research is critical to scaling up efficacious prevention approaches in a way that provides effective coverage for those at risk of HIV acquisition. Having an effective prevention product is not in itself a guarantee of uptake. There is growing consensus that prevention needs to be de-medicalized; people who use it are, after all, not ill. Thus, research on how best to remove barriers to access and use (Box 2) can help identify changes required at different levels of health programming. Furthermore, implementation research can investigate how advances in diagnostics and digital technologies can support shifting prevention delivery to self-care or community cadre, safely and integrated within health programming96–99.

(Box 2) can help identify changes required at different levels of health programming. Furthermore, implementation research can investigate how advances in diagnostics and digital technologies can support shifting prevention delivery to self-care or community cadre, safely and integrated within health programming96–99. Box 4 summarizes priorities for future HIV prevention research that can scale up effective technologies among African women. Communities should be at the center of prioritizing, designing, implementing and evaluating interventions. Citizen science can play an important role in determining why and how deployment is failing or succeeding, as well as helping tailor deployment strategies to specific settings and populations100.

Implementation research is critical to scaling up efficacious prevention approaches in a way that provides effective coverage for those at risk of HIV acquisition. Having an effective prevention product is not in itself a guarantee of uptake. There is growing consensus that prevention needs to be de-medicalized; people who use it are, after all, not ill. Thus, research on how best to remove barriers to access and use (Box 2) can help identify changes required at different levels of health programming. Furthermore, implementation research can investigate how advances in diagnostics and digital technologies can support shifting prevention delivery to self-care or community cadre, safely and integrated within health programming96–99. Box 4 summarizes priorities for future HIV prevention research that can scale up effective technologies among African women. Communities should be at the center of prioritizing, designing, implementing and evaluating interventions. Citizen science can play an important role in determining why and how deployment is failing or succeeding, as well as helping tailor deployment strategies to specific settings and populations100.

Accelerating prevention of new HIV infections among African women and their sexual partners is a global health priority. Recent declines in HIV incidence have been driven by both treatment expansion and combination prevention, underpinned by a growing toolbox of prevention commodities combined with strong understanding of patterns of risk, and how to reach those with the greatest need. The next phase of the response will be driven by three key pillars. First, is to strengthen the implementation of HIV prevention. Implementation research will be needed to drive innovation in developing community leadership models, strengthening delivery platforms, expanding choice (both of products and delivery platforms) and tailoring strategies to address gaps. Second, is to develop and test new products and integrate them within the prevention toolbox. Ongoing research on new longer-acting formulations of antiretrovirals, candidate vaccines and other approaches such as broadly neutralizing antibodies will need innovative methodologies to adapt to the new prevention landscape. Third, is work to both reduce the prices of emerging products and to ensure long-term financing of the response. This must be underpinned by country-specific priorities, cofinancing, modeling and cost-effectiveness research to drive decision-making.