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Sustaining the achievements of the past two decades of global HIV programs and reaching the goal of ending HIV/AIDS as a public health threat by 2030 depend on dramatically reducing new infections. The addition in 2012 of a daily, oral biomedical option—pre-exposure prophylaxis (PrEP)—to the HIV prevention tool kit represented an important step in this direction. Annual HIV infections have declined nearly 40 percent since 2010, but with the rate of decrease stagnating recently, and with 1.3 million new cases in 2023, improving PrEP uptake and making a range of prevention options widely available is urgent. The recent development of highly effective, long-acting PrEP methods makes this a pivotal moment for global HIV prevention efforts. Just as the introduction and scale-up of antiretroviral therapies in the early 2000s offered an opportunity to dramatically shift the trajectory of HIV, there is optimism that it may be possible to significantly reduce new cases of the virus. Success will depend on ensuring a comprehensive set of PrEP options are produced, financed, and delivered in a way that makes them available, affordable, and acceptable to populations most vulnerable to HIV.
For the past 25 years, global HIV response has hinged on a three-pronged approach of disease prevention, diagnosis, and treatment. In the absence of a cure or a vaccine to prevent HIV infection, an emphasis on testing and provision of HIV treatment has been paramount, with programs focused on ensuring access to highly effective antiretroviral therapies. Until relatively recently, HIV prevention centered on reducing the risk of infection by encouraging behavior modification, as well as condom use, and supporting people living with HIV to initiate treatment, improve their own health, and reduce the odds of their transmitting the virus to others.
In the early 2010s, evidence from a series of randomized clinical trials suggested the possibility of using antiretrovirals to prevent HIV infection. Following research that pointed to the efficacy of an approach involving prophylactic use of antiretrovirals, combined with counseling to reduce infection risk, the World Health Organization (WHO) recommended in 2015 the use of a daily oral combination pill as a preventative measure for people highly vulnerable to HIV.1 During the first few years of PrEP programs, the daily oral product was more widely available in high-income countries than in the low- and lower-middle-income countries, where the HIV burden was the greatest to where new infections were increasing the fastest.2 Until the last half of 2020, availability of daily PrEP pills in sub-Saharan Africa was limited and uptake sluggish, but PrEP initiations have accelerated there in the last three years thanks to coordinated efforts by global funders, national governments, and civil society organizations to reduce costs, support procurement, create demand, and deliver services.3 Using PrEP consistently is highly effective in preventing HIV infection, but the fact that more than 40 percent of daily oral PrEP users quit the method within the first six months underscores the importance of better understanding why users may start and stop and how to make additional PrEP options available.4
In the last four years, the WHO has recommended adding two new long-acting PrEP products to the mix of biomedical options available to people at high risk of HIV. These include the dapivirine ring (2021), which is inserted vaginally and replaced every month, and injectable cabotegravir (2022), which is administered every two months.5 Other long-acting HIV prevention products based on existing and new antiretroviral preparations are currently in the research and development pipeline.6
To date, the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), along with the Global Fund to Fight AIDS, Tuberculosis and Malaria and national governments, have provided the greatest momentum in purchasing and promoting the distribution of PrEP commodities in low- and lower-middle-income countries.7 PEPFAR supports the delivery of daily oral PrEP through several programs, including the DREAMS (Determined, Resilient, Empowered, AIDS-free, Mentored and Safe) partnership to reduce HIV/AIDS in adolescent girls and young women. PEPFAR reports that in FY 2023, nearly two million people enrolled to receive PrEP with U.S. government support, an increase of half a million enrollments since 2022.8 The Global Fund has recently joined with the Children’s Investment Fund Foundation (CIFF) to purchase and distribute dapivirine rings in countries eligible for Global Fund HIV and AIDS grants.9 Additional countries are conducting implementation studies in preparation for dapivirine ring introductions.10 And in FY 2024, PEPFAR has supported the introduction of cabotegravir injections in Malawi, Ukraine, Zambia, and Zimbabwe, with plans to reach up to nine additional PEPFAR countries by the end of the year.11 Some upper-middle-income countries less reliant on external funding for PrEP purchases have begun to make cabotegravir for PrEP available, with Botswana, Brazil, China, Malaysia, Namibia, Peru, South Africa, and Thailand having approved cabotegravir and Colombia, Mexico, and Taiwan currently reviewing registration petitions, while a number of other countries conduct implementation studies.12
The arrival of highly effective, long-acting PrEP options makes the current moment a pivotal one for the global HIV response. Just as the introduction and scale-up of antiretroviral therapies in the early 2000s represented an opportunity to shift the trajectory of HIV globally, the availability of a diverse set of prevention options offers the possibility of dramatically reducing new cases of HIV, particularly among young populations between the ages of 15 and 24. The challenge is to avoid delays between the approval and distribution of products in high-income countries versus their availability in low- and middle-income settings, ensuring equitable access in all countries for those who could benefit most. To this end, it is important to learn lessons from the most recent phases of PrEP rollout; support countries’ regulatory, planning, and procurement mechanisms; and engage with civil society to identify PrEP preferences, support the creation of demand for HIV prevention products, and usher in a new era of the global HIV response.
For the past two decades, ensuring people living with HIV are aware of their status and able to access treatment to suppress the virus has been a core objective of global initiatives. Several campaigns have focused on increasing treatment access. An early milestone was the “3x5” initiative introduced by the WHO to focus global attention on ensuring that three million people living with HIV were receiving treatment by 2005.13 In 2013, the Joint United Nations Program on HIV/AIDS (UNAIDS) launched its 90-90-90 goals, which proposed that by 2020 at least 90 percent of people living with HIV would know their status; at least 90 percent of people diagnosed with HIV would be on treatment; and at least 90 percent of the people on treatment would be virally suppressed, meaning they can stay healthy and have a reduced likelihood of transmitting the virus to someone else as long as they remain on antiretroviral medications.14 In 2021, these targets were updated to 95-95-95.15 In 2023, more than 30 million of the 40 million people living with HIV were on antiretroviral treatment.16 Some countries, including Botswana, Eswatini, Rwanda, Tanzania, and Zimbabwe, have met the global 95-95-95 targets regarding diagnosis, treatment, and viral suppression. However, progress has been mixed in other countries, with significant pockets of low treatment coverage at subnational levels. Globally, it is unlikely that the 95-95-95 goals will be met by the end of 2025.17
The treatment-as-prevention concept first emerged in the mid-1990s, when it became clear that providing the drug azidothymidine (AZT) to pregnant women living with HIV could reduce the chances that they would transmit the virus to their babies.18 Starting in 2010, a series of randomized control trials showed that for populations who rigorously adhered to a daily pill regimen, PrEP could be highly effective in preventing HIV infection.19 A 2011 study showed that even in serodiscordant couples, providing antiretroviral therapy to the partner living with HIV and initiating the HIV-negative partner on PrEP, while counseling behavior modification and encouraging safer sex practices, could also effectively prevent transmission of the virus.20 In 2012, the U.S. Food and Drug Administration (FDA) approved the combination antiretroviral pill for HIV prevention, today known as pre-exposure prophylaxis.21
In 2015, the WHO recommended combination antiretroviral therapy as a biomedical prevention option for people at substantial risk of HIV.22 The next year the UN General Assembly Political Declaration on Ending AIDS set a goal of reaching at least three million people at high risk of HIV with PrEP by 2020.23 Recognizing that the 2020 targets were not likely to be met, UNAIDS then put forward a new goal of ensuring 95 percent of people at risk of HIV infection are using combination prevention options by 2025. However, making accurate PrEP coverage estimates can be challenging, as it can be difficult to determine the number of people in a given population at risk of HIV and peoples’ risk can shift over time.24 By 2021, at least two-thirds of countries had adopted the WHO recommendation regarding daily oral PrEP, but countries’ approaches with respect to expanding access to and delivery of PrEP services vary widely, and in some countries the populations who can benefit the most are missing out.25
One set of challenges relates to how the PrEP daily pills have been marketed to HIV-vulnerable populations. Qualitative studies have shown that in some contexts, people who could benefit from biomedical HIV prevention fail to initiate PrEP out of concern that families or friends who learn that they are taking the products will judge them as being engaged in high-risk sexual behavior. In Zimbabwe, for example, the fact that PrEP was initially promoted for men who have sex with men and commercial sex workers created a sense of stigma around its use, leaving some people at risk of HIV reluctant to take PrEP, out of fear of being associated with groups that are criminalized or experience social and political discrimination. Interviews with potential PrEP users in Kisumu County in Kenya revealed that some adolescent girls at risk of HIV were hesitant to take the products out of concern that their parents would instead believe they were taking antiretrovirals to treat the virus.26
How and where PrEP is dispensed impacts initiation and retention as well. The fact that PrEP services are primarily available through HIV clinics in many contexts reinforces potential users’ concerns over being erroneously perceived as living with HIV.27 At the same time, health worker concerns that prescribing PrEP will lead to high-risk sexual behavior and a rise of sexually transmitted infections have led them to limit recommending PrEP for some clients.28 As an alternative, disseminating PrEP through youth-friendly spaces, including DREAMS programs, as well as pharmacies, primary health care settings, or even family planning programs may create space for adolescent girls and young women, in particular, to feel comfortable seeking guidance regarding PrEP and access to the products.29
Beyond concerns over stigma and discrimination associated with HIV, people who desire to take PrEP for HIV prevention can face logistical difficulties in accessing the products. Requirements that daily oral PrEP users return to health clinics for monitoring, testing, or refilling prescriptions on a regular basis (often quarterly, if not monthly) create obstacles, particularly for transient or highly mobile populations.30 Clinic closures or service limitations due to a shortage of health workers who are trained and available to offer the intervention have also created bottlenecks for people motivated to access PrEP services, reinforcing the research finding that providing PrEP through alternative settings may be an important consideration.
Reaching the global goal of ending HIV as a public health threat by 2030 depends on successfully identifying and treating new cases while dramatically reducing new infections. Biomedical methods have assumed an important place in approaches to HIV prevention, but efforts over the past decade to increase access to existing PrEP options outside of high-income countries have been slow to take shape.31 New and forthcoming long-acting PrEP products, including the dapivirine vaginal ring and injectable methods, offer prevention options that may be more discreet than daily pills and require fewer visits to healthcare providers for monitoring and administration. These choices may be preferable to the younger populations at greatest risk of new HIV infections, offering an opportunity to significantly advance prevention efforts. Countries in sub-Saharan Africa are now introducing the vaginal ring and injectable cabotegravir with support from international partners, and there have been calls for manufacturers, governments, and donor organizations to ensure rapid availability of promising new long-acting products, such as twice-yearly injectable lenacapavir for PrEP, if they secure regulatory approval.32
To shorten the period of time between the adoption of new PrEP options in high-income countries and their widespread availability in low- and lower-middle-income settings where new HIV infections are increasing, it will be important to advance efforts simultaneously along three interrelated fronts: (1) regulatory approval; (2) ensuring an adequate and affordable supply; and (3) planning for effective distribution.33
As products are approved in high-income countries and are recommended by the WHO, there is an urgent need to support low- and lower-middle-income countries’ capacities to expedite the movement of new products to regulatory approval and registration. Affordability of approved products is also of critical importance. Ensuring a plentiful and affordable mix of PrEP options will make it more likely that people will find an option that works for them, pointing to the importance of a diverse set of producers, including manufacturing facilities and licensed generic manufacturers, in regions where demand for biomedical PrEP options is likely to be highest. ViiV Healthcare, which produces cabotegravir for PrEP, has inked agreements with three generics firms, via the Medicines Patent Pool, for production of lower-cost versions of their injectable. The developer of lenacapavir, Gilead Sciences, in anticipation of the product's movement through national and regional regulatory processes, announced in October that it had agreed to advance voluntary licensing agreements with six generics manufacturers to facilitate production in low-income countries where there is expected to be demand for the product, if approved.34 Current estimates suggest that generic versions of these products will not be available until 2027. However, without clear indications that there will be a market for their goods, generics producers could take even longer to initiate production.35 To signal to manufacturers that there is demand for their products, governments and health systems must prioritize PrEP and make concrete plans for the purchase and distribution of PrEP methods.36 The development of national and subnational guidelines include training the health workforce to deliver PrEP services in diverse settings, such as youth and key population-friendly clinics, family planning services, and primary healthcare operations. This will reinforce to producers and purchasing agencies that there is a well understood path for product distribution once it has been approved and procured.37
Two groups can play an important role in building greater support for PrEP initiatives in low- and lower-middle-income countries at the intersection of regulatory issues, production, and demand. First, it is essential that community organizations, particularly groups vulnerable to HIV that could benefit most from PrEP, are engaged to share information on product demand with government policymakers, regulators, funders, and implementers to advocate for equitable access to new interventions as they become available. These groups can also share feedback regarding preferences in product design, packaging, or administration directly with manufacturers. Community organizations should be engaged in educating health workers and combatting misinformation about PrEP and PrEP users to make the scale-up of new HIV prevention tools a reality.
Second, the U.S. government, as the largest international donor to global HIV efforts, has an important role to play. U.S. support, through PEPFAR, helps countries prioritize, purchase, and provide PrEP, but the United States can also support countries’ capacities with respect to regulatory approvals and planning processes. PEPFAR can work with community organizations in implementing countries to raise public awareness and build demand for PrEP so that people are educated about HIV prevention options as the various long-acting biomedical tools become more widely available.
Through bilateral programs, PEPFAR has already supported countries in expanding access to PrEP, but as the largest donor to the Global Fund, the United States can also urge and support the fund to do more to expand the range of biomedical HIV prevention options that it supports in eligible countries. As the fund anticipates launching its eighth replenishment round in 2025, the United States can make a robust pledge to support its next three-year cycle of work and encourage other donors to renew funding for the organization. The United States can also encourage the fund to build on its current partnership with CIFF in supporting the introduction of the dapivirine ring and to prioritize assistance for countries interested in expanding the range of long-acting prevention options available through their HIV programs.
Sustaining the achievements of the past two decades of global HIV programs depends on dramatically reducing new infections. The recent introduction or advanced development of new highly effective and long-acting PrEP methods makes this a pivotal moment for the global HIV response. Just as the introduction and scale-up of antiretroviral therapies in the early 2000s offered an opportunity to dramatically shift the trajectory of HIV from one of despair to one of hope, there is increasing optimism that it may be possible to significantly limit new cases of HIV, particularly among young populations living in low- and lower-middle-income countries who represent a sizeable proportion of people highly vulnerable to new infections and who, in the absence of effective prevention, may need to be on life-long antiretroviral treatment. Fulfilling the promise offered by new, long-acting HIV prevention options is not without challenges, but a great deal has been learned since the debut of PrEP in the mid-2010s. Governments, manufacturers, international organizations, and civil society organizations should commit to cooperation now to ensure long-acting PrEP options are produced, financed, and delivered in a way that makes them available, affordable, and acceptable to populations vulnerable to HIV.
Katherine E. Bliss is a senior fellow and director of immunizations and health system resilience with the Global Health Policy Center at the Center for Strategic and International Studies in Washington, D.C.
This report is made possible by Gilead Sciences, Inc., which provided funding.
Special thanks to Carolina Andrada, Corey Donnelly, Anna Russin, Michaela Simoneau, and Christina Zielke for their research assistance in the preparation of this report and to the participants in the CSIS Bipartisan Alliance for Global Health Security Working Group on PrEP for sharing their insights regarding opportunities and challenges associated with expanding access to long-acting PrEP options.
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