FDA Approved: New Long-Acting PrEP Regimen and Its Implications

Alma Mater Cosméticos
Jun 23
30 min read

In June 2025, the US Food and Drug Administration approved a new HIV pre-exposure prophylaxis (PrEP) regimen: the long-acting injectable lenacapavir, marketed by Gilead Sciences under the name Yeztugo . It is the first PrEP drug that offers six months of protection with just one dose, or two subcutaneous injections per year.

This innovative drug belongs to a new therapeutic class – it is an HIV-1 capsid inhibitor , with a multi-sector mechanism of action that is distinct from traditional antiretrovirals. By binding to the virus’ capsid protein (p24), lenacapavir interferes with essential steps of viral replication , including the entry of viral DNA into the cell nucleus, the assembly and release of new viruses, and the proper formation of the capsid core. In other words, it “locks” the capsule that surrounds HIV’s genetic material, preventing the virus from establishing itself and multiplying in human cells. Because it acts at different stages than current drugs, lenacapavir is considered the first in its class .

How does it differ from current PrEP options? Until now, approved PrEP options have primarily relied on daily oral antiretrovirals from the nucleoside reverse transcriptase inhibitor class (such as tenofovir and emtricitabine, found in Truvada® and Descovy®) or, more recently, on long-acting injections every two months of an integrase inhibitor (cabotegravir, brand name Apretude®, from ViiV).

Lenacapavir brings several new features compared to these regimens:

Long-acting PrEP: A single dose of lenacapavir provides protection for six months, outperforming cabotegravir (bimonthly doses) and daily pills. This represents convenience and potential improvement in adherence , as it dramatically reduces the frequency of doses needed.
Route of administration: Lenacavir is administered by subcutaneous injection (under the skin, for example in the abdomen), and there are studies indicating the possibility of self-administration by the patient. Cabotegravir requires intramuscular injection (gluteal) administered by a healthcare professional, and the pills require strict daily use.
Drug class: Because it is a capsid inhibitor, it targets different drugs than current drugs (which inhibit the reverse transcriptase or integrase enzyme). This means that lenacapavir acts at different points in the viral cycle and may offer an option for people who have not adapted to or cannot use previous options.
Efficacy in studies: In Phase 3 clinical trials with thousands of participants, lenacapavir showed extraordinarily high efficacy , with zero HIV infections recorded in the group that received the drug (2,134 participants) against several infections in the control group on daily oral PrEP, demonstrating statistical superiority over daily Truvada. According to Science magazine, which elected lenacapavir as “Scientific Advance of the Year 2024”, the observed efficacy reached ~99.9% in cis men and trans people who have sex with men, and 100% protection in cisgender women in the studies (no infections). In other words, this is an unprecedented result, even surpassing the already high efficacy of injectable cabotegravir (which reduced the incidence of HIV in men who have sex with men by 66% and in women by 89%, compared to oral PrEP in the HPTN 083/084 studies).
Safety profile: To date, lenacapavir has been well tolerated. Some adverse events include injection site reactions , but a small proportion (approximately 0.2–1.2% of participants) discontinued for this reason in the trials. This is likely less frequent or less severe than that seen with cabotegravir, in which pain and nodules at the intramuscular injection site were relatively common. Furthermore, unlike tenofovir, lenacapavir has no known renal or bone toxicities , an important point considering that long-term use of tenofovir (TDF) can cause renal dysfunction and reduced bone density in some cases.

To summarize the differences, the following table compares the main PrEP regimens available or in development and their characteristics:

PrEP option	Type and frequency	Efficacy (clinical studies)	Considerations
Truvada (TDF + FTC) – Gilead	Daily oral tablet	~99% efficacy with high adherence (estimated ~86% in real use)	Widely adopted since 2012; may cause long-term kidney/bone effects.
Descovy (TAF + FTC) – Gilead	Daily oral tablet	Non-inferior efficacy to Truvada (study in MSM and trans)	Approved in 2019; not indicated for receptive vaginal sex (lack of data).
Cabotegravir LA (Apretude) – ViiV/GSK	Intramuscular injection every 2 months (after initial monthly doses)	66% (MSM/trans) and 89% (women) reduction in incidence vs. oral	Approved in 2021 (USA); application by healthcare professional; pain at the application site is common.
Lenacapavir LA (Yeztugo) – Gilead	Subcutaneous injection every 6 months	~100% observed protection (0 infections in 2,134 users)	Approved in 2025 (US); potential self-administration in the abdomen; requires HIV testing before each dose (to avoid resistance).

Legend: TDF = tenofovir (tenofovir disoproxil fumarate); TAF = tenofovir alafenamide; FTC = emtricitabine; MSM = men who have sex with men.

Clinical implications of approval – a new level of HIV prevention

The approval of long-acting lenacapavir marks a watershed moment in HIV prevention . Clinically, the main benefit is to expand the range of PrEP options, increasing the chances of meeting the needs of different patient profiles. Some key points of clinical implications:

Improving PrEP adherence and persistence: It is known that the effectiveness of PrEP depends critically on adherence. Daily regimens face challenges. Many people miss doses or stop taking them due to difficulty maintaining a routine, logistical barriers or stigma.

In Brazil, for example, although the public supply of oral PrEP has grown, it is estimated that around 40% of users abandon oral prophylaxis at some point. Reasons include the need for frequent visits to the health service for testing and pill collection, the obligation to take pills daily at the same time, and the stigma of having a medication associated with HIV at home.

In this context, a twice-yearly injection could circumvent many of these obstacles : people only need to come to the clinic twice a year to get their dose, they don’t have to remember to take a daily pill, and they can continue their prevention in a discreet way. Experts believe that lenacapavir “ could be the transformative PrEP option we’ve been waiting for – with the potential to boost adherence and persistence .”

For vulnerable populations, such as at-risk youth, sex workers, trans people, or drug users, who often face additional challenges maintaining daily regimens, this added convenience could mean more people staying protected at all times .

High efficacy and consistent protection: The clinical data for lenacapavir are encouraging. Keeping nearly 100% of participants free of HIV in studies indicates not only the potency of the drug, but also that, when prevention is simplified , the actual efficacy approaches the theoretical efficacy of the drug. Even Truvada and cabotegravir, which are highly effective, have had some cases of infection in the study arms, often attributed to adherence failures (in the case of Truvada) or exposure during windows without complete coverage.

With lenacapavir, there were no infections while the dose was active. This consistency of protection is especially valuable for vulnerable populations with high HIV incidence, as each failed prevention represents a risk of infection and, consequently, the need for lifelong treatment. It is worth noting that robust efficacy was demonstrated both in men who have sex with men and trans people (in the PURPOSE 2 study) and in cisgender African women (PURPOSE 1 study), population segments in which adherence to oral PrEP has historically been challenging. Therefore, clinically lenacapavir is shown to be relevant for several epidemiological groups .

Need for rigorous monitoring (testing and education): An important clinical implication is to reinforce HIV testing protocols before and during the use of injectable PrEP . Lenacavir comes with a safety warning: it cannot be used in people already infected with HIV , at risk of developing viral resistance. Therefore, before starting the regimen, it is mandatory to confirm a negative HIV serology, and before each biannual injection, repeat the HIV test . This is because, if the individual has acquired HIV and receives a dose of lenacapavir alone (without appropriate combination therapy), the virus could replicate in the presence of the drug and generate resistance mutations.

Clinically, this requires ongoing monitoring and education from health services: injectable PrEP users need to understand the importance of not missing follow-up and testing appointments. In addition, they should be advised on additional safe practices, since PrEP only protects against HIV; other STIs (sexually transmitted infections) still require prevention (condoms, for example).

Potential to reduce new infections at a population level: AIDS leaders see this approval as an important step toward bending the curve of the epidemic . Gilead CEO Daniel O'Day has said that lenacapavir “is the most important tool we have ever had to change the course of the epidemic and put HIV in the history books.” This confidence stems from the idea that if we can bring this innovation to key populations at scale , we can dramatically reduce the annual incidence of infections (currently estimated at ~1.3 million new infections per year globally).

Vulnerable populations, such as men who have sex with men in high-prevalence communities, young women in sub-Saharan Africa, transgender people, sex workers and others, could benefit from a nearly foolproof, long-lasting method – making the UN’s (UNAIDS) goal of Zero New Infections by 2030 achievable. However, this promise depends on factors beyond clinical efficacy, as we will see below.

Challenges and opportunities for access to long-acting PrEP: price, infrastructure and regional inequalities

Regulatory approval in the U.S. is just the first step. Turning this innovation into real public health impact will require overcoming a number of access challenges , especially in low- and middle-income countries where the HIV burden is high.

In this section, we analyze the main challenges and opportunities related to drug pricing, available health infrastructure and regional inequalities , with a special focus on Brazil and the Global South.

Prohibitive price vs. sustainable cost

Currently, the biggest obstacle to the widespread availability of lenacapavir is its extremely high price in high-income markets . Gilead has announced a list price of $28,218 per person per year in the US. This amount, equivalent to more than R$135,000 per year, has caused alarm among activists and international organizations. Pharmacoeconomic studies indicate that the cost of producing a generic version of lenacapavir would be less than $50 per person per year on an industrial scale.

Research published in Lancet HIV estimated that, with demand from 5 to 10 million people, the cost could fall to about $25 per person per year, or less than 0.1% of the listed price in the US. Faced with this discrepancy, UNAIDS Executive Director Winnie Byanyima declared it “ incomprehensible ” to justify $28,000 per year for a drug that could be produced for tens of dollars. She warned that if this revolutionary drug remains inaccessible, it will not revolutionize anything – it will have no impact on the epidemic. UNAIDS, in an official statement, urged Gilead to “ do the right thing: lower the price, expand production and ensure that the world has a chance to end AIDS .”

For developing countries, prices in the tens of thousands of dollars per patient per year are simply unfeasible. For example, Brazil has around 960,000 people living with HIV and an annual rate of new infections of around 40,000 cases (approximate data). The public health budget, despite the commitment to universal treatment, would not be able to cover the cost of extremely expensive prophylaxis for all at risk.

Recognizing this, Gilead announced a differentiated global access strategy: it entered into voluntary, royalty-free licensing agreements with six generic manufacturers (Dr. Reddy's, Mylan/Viatris, among others) to produce long-acting generic versions for 120 low- and lower-middle-income countries .

In these eligible countries, concentrated in Africa, Asia, and parts of Latin America, Gilead promises to provide lenacapavir at no-profit until generics from these licensees become available. Estimates suggest that the no-profit price would be in the range of $150–200 per person per year in these locations.

This is an improvement over the US$28,000, but still significantly above the minimum technical cost (US$25–40) and even above the cost of oral PrEP already in use (for example, South Africa pays about US$40 per patient per year for generic oral PrEP). However, large regions were left out of this generic agreement. In particular, many middle-income countries with significant HIV epidemics are not among the 120 beneficiaries – Brazil is one such case .

Gilead’s criteria focused on “low- and lower-middle-income countries” with high incidence; upper-middle-income countries such as Brazil, Mexico, Argentina, Peru, and others were not included, despite some having actively participated in lenacapavir clinical trials. This exclusion raises concerns about regional inequality : precisely places with concentrated epidemics in key populations and robust public systems (that could implement injectable PrEP) may lag behind in access for some years.

It is worth noting that, historically, Brazil has negotiated inclusion in access initiatives (e.g., for first-line antiretrovirals in the 2000s), but not always with immediate success due to its intermediate economic status and large market.

In the case of lenacapavir, the Brazilian Ministry of Health has already indicated that it will not accept paying the market prices charged in the US or Europe for use as PrEP . Dr. Draurio Barreira, director of the Ministry's HIV/AIDS and STI Department, highlighted that the US price (US$42,000 per year, for the use of lenacapavir in rescue treatment) is “ prohibitive ” and that, for prevention, with a much larger potential user base, the price will have to be different .

A study led by researcher Andrew Hill (University of Liverpool) calculated that a price of around US$94 per patient/year would be plausible for developing countries, considering production costs and a reasonable margin. Brazil has used this evidence in its negotiation strategy.

Health infrastructure and implementation capacity

Another challenge is translating the theoretical availability of the drug into effective real-world programs . Injectable PrEP brings different logistical and infrastructure demands than oral PrEP:

Periodic application system: It will be necessary to have clinics or services capable of administering subcutaneous injections every six months to potentially tens or hundreds of thousands of people. In the Brazilian Unified Health System (SUS), for example, oral PrEP is offered in referral centers and some basic units, but it is not available in all cities .
Expanding to injectable PrEP would require training professionals, securing supplies (needles, syringes, refrigerated storage space if necessary), and scheduling biannual follow-up appointments. The advantage is that the frequency is low (twice a year), which can ease the burden compared to, for example, a monthly injectable. Even so, an adherence schedule must be created, perhaps with the help of information systems, SMS reminders, or apps, to remind users to attend their biannual doses, at the risk of losing protection.
Continuous testing and monitoring: As mentioned, the safety of the regimen depends on 6/6-monthly HIV testing. This implies that the infrastructure must integrate rapid diagnostic services into the flow (4th generation rapid tests or NAT to detect recent infection).
Laboratories and professionals need to be prepared to deal quickly with any positive results, referring for treatment and providing counseling in case of risk exposure between doses (e.g., providing PEP, post-exposure prophylaxis, if a person on PrEP delayed the injection and was exposed to the virus).
Community acceptance and preparation: Effective implementation also involves education and communication . Many potential users may never have heard of injectable PrEP. It will be necessary to explain that the injection is not a vaccine (i.e., protection depends on maintaining it periodically, it does not induce permanent immunity) and that it is still necessary to prevent other STIs .
In Brazil, the experience with the HPV vaccine or even with injectable treatments for other diseases can be used to demonstrate the benefits of biannual convenience. In addition, combating possible myths or fears about injections is necessary. Although studies indicate good acceptance, some people may fear needles or local side effects.
Integration with existing services: One opportunity is to integrate lenacapavir provision into existing HIV prevention and treatment clinics . Testing and counselling centres, sexual health clinics and specialist HIV/AIDS care services could be delivery points. This would leverage experienced staff and existing infrastructure (e.g. fridges, booking systems).
In Brazil, where the SUS already provides antiretrovirals centrally, incorporating injectable PrEP may be feasible in large centers; the challenge will be to expand it to the interior and remote regions. Perhaps partnerships with community NGOs and mobile clinics could help bring injections to populations such as sex workers in mining areas, drug users in communities, etc.

In short, the infrastructure will have to evolve , but the long-acting nature of the drug may make this evolution manageable: with two visits per year per patient, many health systems consider this implementable, especially if there is funding for supplies and staff.

Countries in the Global South with less robust health systems will need technical and financial support (e.g., through PEPFAR and the Global Fund programs) to establish the provision of injectable PrEP. Fortunately, there are initial efforts: PEPFAR and the Global Fund announced in 2024 plans to fund injectable PrEP for up to 2 million people in low-income countries over the next 3 years , in partnership with the Gates Foundation and other donors.

The WHO, for its part, is expediting guidelines and prequalification: it has promised to release new international guidelines on the use of lenacapavir as PrEP in July 2025 and fast-track technical assessment, to guide countries in the safe and effective incorporation of this strategy. These moves indicate an opportunity to coordinate global efforts for implementation .

Regional inequalities: focus on Brazil and the Global South

The case of Brazil exemplifies both opportunities and challenges in inequalities of access. Brazil has historically been a reference in responses to AIDS, was one of the first to offer universal and free antiretroviral treatment in the 1990s, and since 2017 has offered oral PrEP through the SUS.

However, as an upper-middle-income country, it often faces a “gap” between the developed world (which can afford to pay dearly for new technologies) and poorer countries (which receive international support and easier licensing). With lenacapavir, it will be no different:

Gilead has already requested registration with Anvisa (the Brazilian regulatory agency) for the use of lenacapavir in PrEP. According to the Ministry of Health, the company has committed to submitting the formal application in March 2025. Anvisa is expected to review it as a priority (particularly due to its “breakthrough” status abroad). Even so, regulatory and bureaucratic procedures mean that approval in Brazil should occur in the course of 2025 .
Incorporation into the SUS : After health registration, the drug must be evaluated by CONITEC (National Commission for the Incorporation of Technologies) to be included in the SUS protocol. The Ministry of Health itself admits that it would be difficult to offer lenacapavir widely before 2026. This is because, in addition to approvals, there is also the negotiation of price and acquisition.
The government has already begun negotiations with Gilead seeking a fair price agreement or even a specific voluntary licensing for Brazil . Brazilian authorities point out the contradiction of Brazil not being included in the international voluntary licenses , despite having contributed significantly to the research (one third of the participants in one of the PrEP studies were Brazilian).
This exclusion is due, as mentioned, to the presence of Gilead patents in force in Brazil , which legally blocks the production of local generics until at least 2041 (20 years in force). Countries such as India and Argentina, without granted patents, were included in the generic agreements, while Brazil was left out.
Sovereignty and political pressure: Brazil, through its STI/AIDS Program and civil society organizations (such as ABIA – Brazilian Interdisciplinary AIDS Association), advocates the formation of global alliances for access to injectable PrEP and has pressured Gilead to extend licenses or charge differentiated prices for middle-income countries.
There is an underlying ethical-political conflict: on the one hand, the public interest in expanding access to a crucial technology; on the other, the pharmaceutical company’s market interest in safeguarding profits. Veriano Terto Jr., vice president of ABIA, emphasizes that negotiating with Brazil is not the same as negotiating with India: “Brazil has a market of 220 million people, 1 million HIV-positive people, and only the government can negotiate . It is easier for pharmaceutical companies to assert their interests,” that is, to pressure for high prices, since there are no multiple buyers competing.
This conflict has led Brazil to take drastic measures in the past: in 2007, faced with abusive prices, the government issued a compulsory license for efavirenz , breaking the patent and producing the generic locally for the SUS. This was a milestone in the fight against big pharma. In the current case, however, the Brazilian government has signaled that it does not intend to break the patent for lenacapavir – considering that it would be “disrespecting an international trade rule” and could create legal uncertainty for the country. The preferred strategy is dialogue to reach a mutually acceptable agreement. In other words, Brazil seeks a middle ground where Gilead either gives in on the price or licenses local production, avoiding a legal dispute like in 2007.

In the rest of the Global South , we will see differences: low-income countries in Africa and Asia, with donor support, will likely begin receiving generic lenacapavir in 2025-2026 in externally funded pilot programs. Latin American and other middle-income countries will be dependent on individual negotiations.

This increases the risk of inequality in access to cutting-edge technology: countries with more resources or support will have injectable PrEP available years before others. For example, South Africa, Kenya or Nigeria (donor focus countries) may implement lenacapavir before Latin American countries that do not have international funding for PrEP and have to pay for it themselves (such as Brazil, Mexico, etc.).

This asymmetry is a concern for the UN and the WHO; both emphasize the need for global solidarity to ensure that innovation is not restricted. The WHO, in its statement after the FDA approval, called the achievement “important progress” but warned that without a commitment to equitable access, scientific progress will not translate into lives saved .

In short , the access challenge combines economics and implementation capacity . Opportunities exist: international pricing pressure, generic licensing agreements, the engagement of global funders, and the readiness of many health systems to innovate give hope that lenacapavir could begin to benefit populations in the Global South in the coming years.

In Brazil, specifically, success will depend on a balance between firmness and cooperation – using its history of leadership in AIDS to achieve adequate conditions, without giving up what is necessary to protect its key populations.

Impact on public policies, prevention strategies and the role of startups and corporations in the Brazilian healthcare ecosystem

The arrival of a new prevention technology such as lenacapavir has important repercussions on public health policies and the dynamics of the health sector , both public and private.

We will explore how this innovation can shape government prevention policies , influence adopted strategies and what the role of startups and healthcare corporations in Brazil can be in this context.

Public policies and prevention strategies: towards diversification and expansion

In HIV/AIDS policy, there is a growing consensus that a comprehensive “menu” of prevention options needs to be offered to target different audiences and preferences. The introduction of oral PrEP has already changed strategies in recent years, adding to the classic tools (condoms, testing and prompt treatment, harm reduction, etc.). With lenacapavir, health authorities will have the opportunity to further expand combination prevention strategies :

Guidelines and protocols update: Once approved and available, lenacapavir should be incorporated into national prevention guidelines . The Brazilian Ministry of Health will likely issue protocols on who should receive injectable PrEP (e.g., priority populations: MSM, transgender people, sex workers, serodifferent couples, young people at high vulnerability), how to offer it (specialized centers initially, perhaps gradually expanding to primary care), and requirements (testing, informed consent on the novel nature, etc.).
This formal inclusion is crucial for states and municipalities to plan programs and budgets. Neighboring and other middle-income countries will also face similar debates. The WHO, as mentioned, plans to provide global guidance soon, which will help inform national policies.
Expanding the scope of prevention: With a biannual option, there is an opportunity to recruit people who have not adhered to oral PrEP for prevention . This can influence program goals and indicators. For example, Brazil has a goal of significantly increasing the number of people on PrEP to help reduce new infections. However, it faces limits on adherence to the daily pill (currently ~110,000 people use PrEP in the country, a number still below the potential).
Public policy can direct communication efforts to publicize the new option, advertising campaigns, mobilization on social networks and partnerships with community NGOs, emphasizing that “if taking it every day is difficult, now there is an alternative of taking it twice a year”.
By reaching new segments with this message, we hope to expand the audience engaged in PrEP . Prevention strategies can be restructured to offer each individual’s preferred option , increasing overall effectiveness: some will continue to prefer the autonomy of the daily pill (especially if they do not have easy access to twice-monthly clinics), while others will switch to the injection.
Targeting key populations and reducing internal inequalities: Policies could target lenacapavir primarily to populations with higher HIV incidence or greater difficulties with current methods . For example, young cisheterosexual women in some regions of Brazil (North/Northeast) have increasing infection rates and low adherence to oral PrEP, possibly due to cultural and gender issues. A public strategy could prioritize introducing PrEP biannually in these groups, in pilot projects, to assess the impact.
The same goes for trans populations, who are sometimes reluctant to take daily pills due to interactions with hormone therapy or fear of revealing their sexual status to family members. Offering a discreet, twice-yearly injection in a supportive environment can be transformative. Innovation can thus tailor policies to niches, with the potential to reduce disparities : those who did not benefit from the previous method can benefit from the new one.
End the epidemic goal: In line with initiatives such as “ Ending the HIV Epidemic ” and UN targets (95-95-95, among others), public policies can integrate lenacapavir into plans to eliminate HIV transmission. For example, some cities or states can adopt the goal of “no new infections in X years” focusing on high coverage of combined PrEP (oral + injectable).
Brazil has advocated internationally for a global alliance for access to injectable PrEP by 2024 precisely because it understands that, without democratizing innovations, it will not be possible to end AIDS by 2030. In short, the policy is adjusted to incorporate the best available science in the pursuit of ambitious public health goals.

Role of the private sector, startups and healthcare corporations

In the Brazilian healthcare ecosystem, the public sector has traditionally led the response to HIV. However, the innovation of lenacapavir also opens up space for healthcare startups, companies and public-private partnerships to act in a complementary manner:

PrEP/adherence-focused startups and healthtechs: We may see startups developing technology solutions to support injectable PrEP . For example, mobile apps that manage the user’s calendar, send reminders about the next injection, automatically schedule appointments, and even offer telecounselling.
There are already healthtechs in Brazil that work in prevention and patient monitoring (including telemedicine services in HIV/PrEP). With the arrival of biannual PrEP, these companies can adapt their platforms to meet this new need for long-term monitoring.
In addition, startups can work on digital education : creating informative content, chatbots to answer questions about PrEP, and online communities to share experiences, reducing anxiety and stigma. All of this complements the clinical offering of the SUS, keeping users engaged and informed.
Private clinics and corporate services: Until the SUS incorporates lenacapavir (or beyond its capacity), the private sector will likely step in. Health plans and private clinics may import or purchase the drug (once registered) to offer to clients who can afford it. Although the cost is high, there is a portion of high-income supplementary or private health clients who may require immediate access.
This could create a private market for early injectable PrEP , similar to what has happened with some newer-generation antivirals, which were first available in private clinics and hospitals. Startups could explore subscription models for PrEP, for example, a service in which the customer pays a monthly fee that covers the doctor’s visit, regular tests, and, every six months, the injection of lenacapavir. Healthcare corporations (private hospitals, laboratory networks) could also get involved by providing injection sites and integrating PrEP into their primary care programs.
It is important that, even in these commercial contexts, there is alignment with official guidelines to ensure safety and that data (for example, new HIV cases avoided or possible failures) are communicated for epidemiological surveillance.
Partnerships and corporate social responsibility: Big pharma, including Gilead itself, as well as corporate foundations, can play a role through access and education programs . Gilead, for example, has announced a co-pay and donation program for uninsured individuals in the U.S., ensuring that even the uninsured can access Yeztugo for free.
In Brazil, despite the public system, we could imagine collaborations in which Gilead supports implementation studies, donating a certain number of doses for demonstration projects in key populations, or training health professionals through educational programs. Other corporations with a focus on public health (such as foundations and NGOs supported by the private sector) could fund awareness campaigns about the new tool, reducing stigma and increasing informed demand. This benefits the ecosystem as a whole; the greater the awareness and demand, the more positive pressure to accelerate supply in the SUS.
Local innovation and national production: A relevant chapter will be whether any Brazilian corporation or institution will be able to produce lenacapavir locally in the future. Given the patenting, this will depend on agreements or the expiration of the patent. Institutions such as Fiocruz/Farmanguinhos have historically produced generic antiretrovirals for the SUS, and national generic companies have technological capacity.
If the negotiations between the government and Gilead include technology transfer or licensing for production in Brazil (even if only for internal consumption by the SUS), this would strengthen the country's autonomy and could even supply the South American region. Although there is no concrete indication of this to date and Gilead has excluded Brazil from global voluntary licenses, it remains a strategic possibility in the medium term, especially if the price remains prohibitive.
National biotechnology startups could also, in theory, research analogous molecules or alternative forms of administration (for example, long-lasting subdermal implant formulations with lenacapavir have already been considered in research). All of this would position Brazil not only as a consumer, but also as an actor in the development of the next-generation prevention ecosystem.

In short, the arrival of lenacapavir should stimulate both the public and private sectors to innovate: public policies adjusting to incorporate the novelty and maximize its impact, and private players and startups creating support solutions, expanding access in niches and complementing where the public authorities are slow to arrive.

The ultimate goal, shared by all, is to reduce HIV transmission . If each actor plays its part – government ensuring equity and scale, corporations collaborating on prices and programs, startups making life easier for users – the Brazilian healthcare ecosystem can make a qualitative leap in HIV prevention.

What is still missing in the fight against HIV/AIDS: vaccine and cure, the persistent challenges

Despite all the excitement surrounding long-acting injectable PrEP, it is crucial to remember that it is not a cure for HIV or a vaccine . It is yet another highly effective preventive tool, a huge step forward, but the fight against the epidemic still has important gaps that remain unsolved.

Here we reflect on what is still missing and the ongoing scientific challenges, especially in the development of a preventive vaccine and a cure for HIV .

The search for an effective vaccine

Forty years have passed since the discovery of HIV, and to this day there is no approved preventive vaccine against the virus. Several attempts have reached advanced stages, but all have failed to demonstrate satisfactory efficacy. In January 2023, for example, the Mosaico phase 3 study, supported by Janssen (Johnson & Johnson), which was testing a vaccine regimen on thousands of volunteers in several countries (including Brazil), was interrupted. An interim analysis revealed that the vaccine did not protect against HIV better than placebo . This was yet another disappointment that added to others: since the 2000s, at least eight large vaccine trials have reached phase 3 and none have achieved significant success .

This illustrates the tremendous complexity: HIV is a highly genetically variable virus capable of rapid mutation and immune evasion . It attacks the immune system itself, making inducing lasting immunity extremely difficult. As researcher Dr. Brenda Crabtree put it, “In 40 years we have only managed to reach eight phase 3 trials, all with disappointing results... HIV is the most difficult pathogen to defeat.”

However, there is no giving up . The scientific community continues to explore new approaches: new-generation vaccines using mRNA vectors (a technology that has proven successful in COVID-19) are in the early stages of study for HIV; broadly neutralizing immunogens (capable of stimulating antibodies against multiple strains of the virus) are also being researched.

Until a vaccine is available, experts stress that we should use everything that already works – and that is where tools such as PrEP (oral or injectable), testing and treatment (undetectable = untransmittable) and sexual education come in. The eventual arrival of an effective vaccine would greatly simplify prevention, but after so many setbacks, the overall strategy is not to depend on it.

The watchword has been: keep trying to develop vaccines, but don’t count on them in the short term . Therefore, the innovation of lenacapavir partially fills the gap in the absence of a vaccine, offering a highly effective way to prevent infections, but we still need this “Holy Grail” to declare complete victory.

The challenge of definitive healing

Another battlefront is the search for a cure for HIV . Today, antiretroviral treatment can control the virus to the point of making it undetectable and non-transmissible, but it remains latent in the body . HIV settles in “ viral reservoirs ”, long-lived cells (such as memory T cells, macrophages, and tissues such as lymph nodes and the brain) where the virus’s DNA remains dormant. Current medications do not eliminate these reservoirs. Therefore, if treatment is interrupted, the virus starts replicating again.

Sterilizing cure (complete elimination of the virus from the body) has proven to be extremely difficult. To date, only a few exceptional cases, the famous “Berlin patients”, “London patients” and others, have achieved a functional cure after bone marrow transplants from HIV-resistant donors. These procedures are risky and cannot be replicated on a large scale.

For a comprehensive cure, research explores several strategies:

“Kick and kill”: drugs or agents that “wake up” latent HIV in reservoirs (kick), and then eliminate it via immune response or targeted therapies (kill). Trials with latency-reversing drugs + neutralizing antibodies are ongoing, but so far they have not completely eradicated the virus.
Gene editing: Using tools like CRISPR to remove proviral DNA from cells or make cells immune to infection (e.g., by editing the CCR5 gene in a patient’s T cells). There have been early studies, including a first human trial of CRISPR in 2022, but it is still in the experimental stage.
Immunotherapy and broad-acting antibodies: Trying to induce the immune system to control the virus without ongoing medication. Some patients in studies achieved prolonged HIV remission after receiving combination broadly neutralizing antibodies, but most still experienced viral rebound after some time.

Dr. José Valdez Madruga, a Brazilian researcher who coordinated studies on lenacapavir in the country, stressed that lenacapavir is not a cure for AIDS and does not claim to be. He explained that in order to cure the disease, it would be necessary to eliminate the latent virus from the reservoirs , something that lenacapavir does not do. The drug only works by preventing new infections of cells, but does not “wipe” the virus out of the body .

Furthermore, this is not a vaccine. It does not train the immune system, it simply blocks the virus directly. These distinctions underscore that even with long-term PrEP and excellent treatments, HIV infection remains incurable in the individual , and we need to continue investing in science so that, perhaps one day, we can definitively cure the ~39 million people living with HIV in the world.

In short, we still lack a vaccine and a cure , two dreams we have had since the beginning of the epidemic. The difficulties encountered so far demonstrate the resilience of the virus and the need for scientific persistence. Until these goals are achieved, each new advance (such as lenacapavir in prevention, or new classes of antiretrovirals in treatment) is essential to maintain control of the epidemic and save lives. But we cannot confuse great progress – however celebratory it may be – with the end of the road. The fight against HIV/AIDS continues, driven by innovations such as this, but aware of the remaining obstacles.

Ethical, regulatory and commercial implications of Big Pharma dominance

The approval of lenacapavir and the debate surrounding its access raise a larger issue: the role and dominance of big pharma in the HIV field – and the ethical, regulatory and commercial implications of this. Let’s consider some thoughts:

Innovation monopolies and unequal access

Innovative medicines like lenacapavir are the result of massive R&D investment, largely by large companies (in this case, Gilead Sciences). In recognition of this, the global patent system grants these companies a temporary (usually 20-year) monopoly on commercialization. From a commercial perspective, this provides financial returns and encourages innovation. However, from a global public health perspective, it creates a situation where a single entity controls who can produce and at what price , potentially for decades, even as lives are at stake.

Ethically, there is a conflict: to what extent is it acceptable for a crucial scientific breakthrough to end an epidemic to be kept out of reach of millions because of market considerations? The case of lenacapavir exemplifies this: Gilead holds patents in key countries (such as Brazil), excluding them from generic licenses. The company committed to licenses in poorer countries and a “no-profit” price in those places, which is commendable, but it went only as far as its interests allowed .

Countries that are “too rich” to receive cheap generics but “too poor” to pay high prices are left in limbo. This pattern has already been seen with other drugs (for example, the new hepatitis C antivirals, or even cabotegravir). Internationally, there is debate about whether it would be necessary to reform patent rules or pricing mechanisms for public health situations, for example, using compulsory licenses more frequently (which involves sensitive regulatory and diplomatic aspects) or creating multilateral agreements to set maximum prices in certain countries. At the moment, however, big pharma still dictates the initial rules, leaving it up to governments and international organizations to react on a case-by-case basis.

Social responsibility vs. shareholder interest

Pharmaceutical companies often point to their access initiatives as evidence of social responsibility (such as Gilead’s voluntary royalty-free licenses, or donations). These measures undoubtedly expand the reach of medicines and save lives. However, they are voluntary decisions by companies, not obligations.

This means they are subject to commercial considerations: lucrative markets tend to be left out, negotiations can be tough (countries sometimes accept restrictive clauses to obtain small price concessions). Ethics enter the discussion when it is asked: should a preventive medicine that can end a pandemic disease be treated as a common commodity or as a global public good ?

UNAIDS, in its statement, emphasized that lenacapavir is the result of “decades of public investment, scientific excellence and contributions from communities and volunteers.” In other words, although the company developed it, there was government funding and thousands of people participated in the tests.

This suggests that there is a moral duty to make it widely available . UNAIDS’ Byanyima was emphatic in saying that if it remains expensive and inaccessible, “it will not change anything” in the course of the epidemic. Companies have a duty to generate profits for their shareholders, but they also operate in a sector with a strong social impact. This tension is ongoing and is reflected in negotiations with governments: in the Brazilian case, we see the search for a “ fair price ” rather than impositions, that is, appeals to the company’s reasonableness and long-term interest in having a product widely used (which, by the way, can also be good for business, if lower prices allow for much larger volumes).

Regulation and speed of global approval

The FDA gave fast-track approval to lenacapavir, with priority review and breakthrough designation , recognizing its importance. However, other countries rely on their own regulatory agencies (such as ANVISA in Brazil, EMA in Europe, etc.) or await guidance from the WHO.

Here, the dominance of big pharmaceutical companies manifests itself in another way: the availability of data and the interest in regulatory submission . If a company decides not to submit a registration in a country (for example, because it finds the market unprofitable), that country is left without options until a generic becomes available years later.

Fortunately, Gilead has announced broad regulatory submissions, including in Brazil, Australia, Canada, South Africa, etc., in part due to global pressure. But there have been cases of drugs that have been delayed in reaching certain markets due to lack of initiative by the holder.

Regulators in countries in the Global South also face the challenge of quickly assessing and approving a complex product, sometimes without full access to all the data (which the company tends to submit first in the US/Europe). The WHO, by preparing guidelines and prequalification, acts to mitigate these asymmetries , serving as a reference for countries to trust the data of others and not delay adoption.

From an ethical perspective, pharmaceutical companies are expected to collaborate with regulatory authorities globally , submitting quality dossiers and participating in collaborative mechanisms (such as AVAREF in Africa, or other coalitions of agencies) to accelerate approvals in countries with lower regulatory capacity.

Commercial: impact on competition and future innovation

The introduction of lenacapavir also has commercial implications for the competitive landscape of HIV prevention . Until now, Gilead dominated the PrEP market with Truvada/Descovy, but was about to lose exclusivity on Truvada (which already has generics) and faced competition from ViiV’s cabotegravir (Apretude).

With lenacapavir, Gilead is regaining its leading role, as it offers a product with superior and patented attributes. There will be strategic consequences : ViiV/GSK may accelerate next-generation research (perhaps a quarterly cabotegravir or another molecule) to avoid losing ground. Other companies may invest in alternatives (Merck had a candidate, islatravir, which is in studies but faced safety concerns in 2021).

For the end user and healthcare systems, competition is usually beneficial. Ideally, several competing manufacturers would lead to lower prices. However, in this cutting-edge prevention niche, we have few players and each one has a unique product (temporary monopoly in each class). Thus, the commercial dynamics tend to be one of coopetition and agreements.

For example, Gilead licensing generics can keep it as the “branded” supplier in rich and middle-income countries (by charging a high price), while allowing generics in poor countries (where ViiV also made a similar deal for cabotegravir with the Medicines Patent Pool). These large corporations end up defining among themselves how the global market will be segmented.

This raises regulatory and ethical questions about transparency : it would be important for the terms of these agreements (which countries are included/excluded, criteria) to be clear and subject to review by international bodies, to avoid injustice and undue influence.

Role of civil society and advocacy

Finally, it is worth noting that the dominance of big pharma is not absolute; historically, pressure from activists, NGOs and international organizations has forced significant changes.

In the 2000s, the fight for first-line generic HIV drugs forever changed the way companies license drugs in poor countries.

Today, with lenacapavir, we have seen this pressure since day one of approval: UNAIDS publicly demanding fair pricing, groups like ABIA in Brazil asking for inclusion in licenses, and even articles in major newspapers questioning the pricing policy (a headline in The Guardian even called lenacapavir a “drug to end HIV” that could cost US$25 but is at risk of being unaffordable). This public scrutiny is part of the ethical implications, holding companies accountable for the global impact of their products.

In conclusion, big pharma like Gilead plays a dual role: as a driver of innovation (thanks to investments and scientific capacity) and as a gatekeeper of access (by holding patents and supply). Balancing profit and public health is the central dilemma.

In the case of long-acting PrEP, we are seeing a movement to tip the balance in favor of life and equity: to share the benefits of science as widely as possible. Regulators, NGOs, governments, and companies themselves need to collaborate, and sometimes clash, to ensure that commercial dominance does not impede epidemic dominance . Only then can the groundbreaking approval of lenacapavir fulfill its potential to go down in history as a turning point in the fight against HIV/AIDS, rather than as yet another example of a life-saving technology that is inaccessible to those who need it most.

The approval of lenacapavir, Gilead’s new long-acting PrEP regimen, marks the end of a promising phase and the beginning of another full of transformative possibilities in HIV prevention. With just two annual doses offering near-complete protection, this breakthrough brings renewed hope, but also challenges us: how can it be integrated equitably into the health innovation ecosystem in Brazil and the Global South?

True to the mission of the Brazilian Institute of Innovation in Health - IBIS to promote qualified dialogue among health innovators, we invite you to reflect with us and share your opinions, experiences or proposals in the comments. What future do you envision for HIV prevention in Brazil and the Global South?

References:

Gilead Sciences. Yeztugo® (lenacapavir) Is Now the First and Only FDA-Approved HIV Prevention Option Offering 6 Months of Protection. Press release, June 18, 2025.
Reuters. US FDA approves Gilead's twice-yearly injection for HIV prevention. June 18, 2025.
Wikipedia (Lenacapavir). Mechanism of action – description of the capsid inhibitor action; History – recognition of lenacapavir as Breakthrough of the Year (Science, 2024) and efficacy data; Economics – US price and generic cost estimates.
Medscape (in Portuguese). Lenacapavir should not be incorporated into the SUS before 2026. Washington Castilhos, January 21, 2025. – Interview with the Ministry of Health about registration with Anvisa and incorporation; discussion of price in the US (US$42,000) vs. need for lower price for PrEP; study by Andrew Hill suggesting US$94/year; voluntary licensing agreements and exclusion from Brazil; ABIA’s comment on public vs. private conflict; reference to the compulsory licensing of efavirenz in 2007; the Brazilian government’s position against breaking the patent for lenacapavir; data on adherence to oral PrEP in Brazil (110,000 users, 40% abandonment) and reasons; description of the injection regimen (2x yearly, 1.5mL, potential self-administration in the abdomen); clarification that it is neither a cure nor a vaccine, by Dr. Valdez Madruga; comparison between cabotegravir and lenacapavir – advantages of self-administration, less pain, semiannual vs. bimonthly dose; approval rating for cabotegravir in Brazil (2023) but not yet available in the SUS; expectation of both being made available via the SUS with negotiation.
UNAIDS. Press Release: UNAIDS urges Gilead to drop price of new HIV prevention shot. 18 June 2025 – Highlighting FDA approval and list price of US$28,218; Lancet HIV study on generic cost of US$25-35; statement by Winnie Byanyima on need for affordable price for lenacapavir to have impact.
International Health Policies Newsletter (Excerpts, 2025) – Notes on PEPFAR/Global Fund plans to finance 2 million people with lenacapavir; no-profit price of US$150-200 in the 120 licensed countries vs. US$40 paid per oral in South Africa; exclusion of middle-income countries (Brazil, Peru) from access to generics despite significant epidemics; mention of WHO guidelines being developed by July 2025.
HPTN 083/084 – Efficacy results of injectable cabotegravir compared with oral PrEP: ~66% (MSM and trans women) and ~89% (cis women) reduction in infections.
TheGuardian. 'HIV-ending' drug could be made for just $25 per patient a year, say experts. June 17, 2025 (quoted via IHP newsletter).
Matías Loewy, Medscape in Portuguese. HIV vaccine trial halt causes 'frustration' but not resignation. February 21, 2023 – Details of Mosaico trial cancellation due to lack of efficacy; history of vaccine failures (8 phase 3 trials in 40 years, all unsuccessful); statements from researchers emphasizing complexity and need to keep trying.