Understanding Preventative HIV Treatments: What You Need to Know

Summary

Preventative HIV treatments encompass a range of biomedical strategies designed to reduce the risk of HIV infection through the use of antiretroviral medications either before or after potential exposure. Key modalities include pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), and treatment as prevention (TasP). These interventions have transformed HIV prevention by significantly lowering transmission rates in diverse populations worldwide, including men who have sex with men (MSM), serodiscordant couples, and high-risk groups in resource-limited settings.
PrEP, available as daily oral pills or long-acting injectable formulations such as cabotegravir and the recently FDA-approved lenacapavir, offers highly effective prophylaxis when adherence is maintained. PEP serves as an emergency short-term intervention initiated within 72 hours after potential HIV exposure, while TasP involves sustained antiretroviral therapy for people living with HIV to maintain viral suppression and virtually eliminate sexual transmission risk (“undetectable equals untransmittable”). Comprehensive HIV prevention also integrates vaccination, co-infection management, and behavioral counseling to address broader health needs.
Despite these advances, significant disparities in access and uptake persist, particularly among marginalized populations such as Black and Hispanic communities, transgender individuals, and people who use illicit drugs, especially in the United States. Barriers including stigma, healthcare infrastructure limitations, and cost challenges constrain widespread adoption, notably of long-acting injectables, which require clinic-based administration and remain costly. Efforts to expand equitable access focus on enhancing healthcare capacity, addressing social determinants, and implementing culturally competent care.
Ongoing research aims to improve prevention options through novel long-acting agents and broadly neutralizing antibodies, while national initiatives like the Ending the HIV Epidemic program target substantial reductions in new infections by 2030. A person-centered approach that tailors prevention strategies to individual risk and social contexts is central to optimizing the effectiveness of HIV preventative treatments worldwide.

Background

Understanding the perspectives and preferences of individuals eligible for pre-exposure prophylaxis (PrEP) is essential for designing effective HIV prevention programs that meet clients’ needs. While many PrEP initiatives in resource-limited settings have targeted specific populations through partner organizations, some governments, such as Zimbabwe’s, aim to expand PrEP availability to broader populations at substantial risk by integrating services into public sector clinics.
Having data on the background rate of HIV diagnosis among those not on PrEP enables comparisons between observed new HIV cases following interventions and expected rates over time. This comparison is valuable for evaluating the impact of prevention efforts, including federal programs aimed at increasing PrEP coverage in selected counties and states. Moreover, such data facilitate the computation of HIV incidence rates related to specific risk factors.
Despite four decades of advances in HIV treatment and prevention, the epidemic continues to disproportionately affect certain groups, including Black and Hispanic communities, men who have sex with men (MSM), transgender individuals, and people who use illicit drugs in the United States. National initiatives like the Ending the HIV Epidemic (EHE) program have set ambitious goals to reduce new HIV diagnoses by 2030, emphasizing the importance of addressing disparities in prevention access and uptake.
PrEP has demonstrated high efficacy in various populations, such as MSM and HIV-serodiscordant heterosexual couples, with effectiveness rates reaching up to 86% in studies conducted in the United Kingdom, France, Canada, Uganda, and Kenya. Increasing PrEP use has contributed to a notable decline in estimated HIV transmissions; for example, targeted jurisdictions experienced a 21% reduction from 2018 to 2022, alongside steady increases in PrEP uptake since 2014, with about 200,000 people receiving it monthly in 2023.
Comprehensive HIV management also includes preventive measures beyond PrEP, such as vaccinations (e.g., influenza, pneumococcal), screening and treatment of co-infections, and counseling on safe sex practices to reduce HIV and other sexually transmitted infections. In addition to PrEP, other prevention strategies include nonoccupational post-exposure prophylaxis (nPEP), a short-term antiretroviral regimen following potential HIV exposure, and Treatment as Prevention (TasP), where HIV-positive individuals use antiretroviral therapy to maintain health and reduce transmission risk.

Types of Preventative HIV Treatments

Preventative HIV treatments encompass several strategies aimed at reducing the risk of HIV infection by using antiretroviral medications either before or after potential exposure. The primary types of preventative treatments include Post-Exposure Prophylaxis (PEP), Pre-Exposure Prophylaxis (PrEP), and Treatment as Prevention (TasP).

Pre-Exposure Prophylaxis (PrEP)

PrEP involves the regular use of antiretroviral medications by HIV-negative individuals at substantial risk of acquiring HIV. It is designed to prevent the establishment and spread of HIV in the body if exposure occurs. PrEP can be administered daily via oral pills or as long-acting injectable formulations. Currently, two oral tenofovir-based medications and two FDA-approved injectable forms are available, with injectables administered either every two months or twice yearly. In June 2025, the FDA approved injectable lenacapavir (LEN), administered biannually, based on clinical trials demonstrating efficacy rates of 100% in females and 96% in primarily male populations over one year of follow-up.
While PrEP is highly effective when taken as prescribed, challenges such as adherence and persistence with the medication regimens remain. Strategies to improve adherence include fostering clinician-patient trust and open communication, as well as tailoring approaches to individual circumstances. It is important to note that oral PrEP does not protect against pregnancy or other sexually transmitted infections (STIs).
Some individuals may use alternative dosing strategies, such as the 2-1-1 dosing regimen, which involves taking doses around the time of sexual activity. However, this approach is off-label and not FDA-approved, with recommendations to restrict its use to specific populations who can adhere to the complex regimen.

Post-Exposure Prophylaxis (PEP)

PEP refers to the short-term use of antiretroviral medications immediately following a possible exposure to HIV, with the goal of preventing infection. It is most effective when initiated as soon as possible after exposure, ideally within two hours, and must be started no later than 72 hours post-exposure. PEP is typically prescribed as a 28-day course and is considered an emergency intervention rather than a routine preventive measure. It is commonly used after occupational exposures, such as needlestick injuries, or nonoccupational exposures, including sexual contact or injection drug use. However, PEP is not recommended for individuals who experience frequent exposures to HIV, as other preventative methods may be more appropriate.

Treatment as Prevention (TasP)

TasP is a preventative strategy based on treating individuals living with HIV to achieve and maintain an undetectable viral load, which effectively eliminates the risk of sexual transmission of the virus. The concept of “undetectable equals untransmittable” (U=U) underlies this approach, emphasizing that effective antiretroviral therapy not only benefits the health of the person living with HIV but also serves as a powerful tool to prevent onward transmission.

Additional Preventative Measures

In addition to pharmacological interventions, comprehensive HIV management includes vaccinations (such as influenza and pneumococcal vaccines), screening and treatment of co-infections, and counseling on safe sex practices to reduce transmission risks. Person-centered HIV prevention emphasizes individual choice and acknowledges that prevention needs may evolve over time due to personal and structural factors. Effective clinician engagement is essential to support prevention strategies tailored to each individual’s circumstances.

Mechanism of Action

Preventative HIV treatments primarily function by utilizing antiretroviral drugs to inhibit the replication and spread of the virus within the body. Antiretroviral therapy (ART), the standard treatment for HIV infection, works by suppressing viral replication, aiming to achieve and maintain viral suppression where the HIV levels in the blood become undetectable or very low. This suppression helps slow the progression of the infection, preserve immune function, and prevent the development of AIDS.
Pre-exposure prophylaxis (PrEP) involves taking antiretroviral medications by individuals at high risk of HIV exposure to prevent the virus from establishing infection. PrEP stops HIV from taking hold and spreading throughout the body when taken consistently as prescribed. Its protective effect persists only while the medication is being taken; discontinuation results in loss of this protection.
Post-exposure prophylaxis (PEP) is a short-term emergency regimen of antiretroviral drugs taken after a potential HIV exposure. When initiated promptly—ideally within two hours and no later than 72 hours post-exposure—PEP effectively prevents HIV infection by inhibiting viral replication during the initial stages of potential infection. Rapid administration is critical for its success, and PEP is not intended for frequent use as a prevention strategy.
Treatment as prevention (TasP) utilizes antiretroviral therapy in people living with HIV to maintain viral suppression, thereby keeping individuals healthy and significantly reducing the risk of transmitting the virus to others. TasP is an evidence-based strategy that complements concepts such as “undetectable equals untransmittable” (U=U), emphasizing that sustained viral suppression prevents sexual transmission of HIV.

Eligibility, Screening, and Recommendations

Eligibility for HIV preventative treatments such as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) is guided by risk assessment and clinical judgment, supported by evidence-based recommendations from multiple health organizations. The US Preventive Services Task Force, along with HIV professional associations including the Centers for Disease Control and Prevention (CDC), have developed guidelines for HIV screening and the use of preventative therapies in both the general and specific populations.
Routine and repeat HIV screening is recommended for adults, adolescents, and pregnant people in healthcare settings to identify those who may benefit from preventative treatments. Screening plays a critical role in early detection and timely initiation of interventions, thereby reducing transmission risks.
PrEP eligibility primarily targets individuals without HIV who are at substantial risk of exposure. This includes those who have been prescribed non-occupational PEP (nPEP) multiple times, indicating repeated potential exposure to HIV, and who can benefit from a daily oral regimen to effectively reduce infection risk. Uptake and adherence to PrEP depend heavily on perceived risk and personal circumstances; for instance, in sub-Saharan Africa, clients have reported that PrEP offers a discreet HIV prevention method, especially when negotiating condom use is difficult. However, stigma remains a significant barrier to PrEP continuation in many settings.
PEP, on the other hand, is intended as a short-term emergency intervention that must be started within 72 hours after a possible HIV exposure to be effective. It is not suitable for frequent exposures but is recommended in specific cases such as occupational exposure or community incidents like needlestick injuries from discarded needles. The risk assessment for needlestick injuries includes factors like the type of needle, presence of blood, and skin penetration. Clinical guidelines emphasize prescribing effective, well-tolerated PEP regimens and addressing challenges to regimen completion to maximize effectiveness.
Comprehensive HIV prevention strategies involve not only identifying eligible individuals through screening but also ensuring access to and support for adherence to PrEP and PEP regimens. Programs continue to evolve to meet the needs of diverse populations, with increasing efforts to integrate HIV prevention services in public health settings worldwide.

Access, Availability, and Cost

Access to preventative HIV treatments such as long-acting injectable PrEP, including cabotegravir and lenacapavir, remains uneven across different regions and populations. In the United States, between 11,000 and 14,000 initiations of cabotegravir have been reported, while access is largely limited outside the US except in countries like South Africa, Zambia, and Malawi. Despite the US having comparatively higher usage rates, scaling up cabotegravir access faces significant hurdles including complex insurance prior authorization processes, absence of state-funded PrEP programs, and the need for additional healthcare staff. Furthermore, the requirement for clinic-administered bimonthly injections complicates delivery, underscoring the demand for longer-acting injectable formulations to simplify roll-out.
Cost remains a critical factor influencing availability and uptake. Current pricing data indicate that the active pharmaceutical ingredient (API) for lenacapavir is exported from India at approximately $64,480 per kilogram on a 1 kg scale. However, cost of goods sold (COGS) could be significantly reduced to $25,000/kg or even $10,000/kg with higher production volumes and competitive generic licensing. This could translate to mass production costs of around $94 or $41 per patient per year for 1 million and 10 million treatment-years, respectively, if voluntary licenses and generic competition improve. Despite this potential for lower costs, long-acting injectables like lenacapavir are still considered relatively expensive compared to their modest incremental impact, posing challenges for widespread adoption unless drug pricing policies evolve.
Barriers to equitable access extend beyond cost and include social and systemic factors such as stigma, discrimination, lack of education, and insurance hurdles. These issues particularly affect underserved communities, including Black and Hispanic/Latinx populations, who are less likely to receive PrEP compared to White males. Although under the Affordable Care Act PrEP is provided free under most health insurance plans without co-payments or deductibles, disparities in coverage and uptake persist. Efforts to increase healthcare capacity, expand the workforce, and incorporate diverse healthcare professionals aim to improve access, especially in underserved regions such as the southern US and rural areas.

Side Effects, Safety, and Drug Interactions

Like all medications, pre-exposure prophylaxis (PrEP) can cause side effects, although not everyone experiences them. The most common side effects usually occur in more than 1 in 100 people and often resolve within the first few weeks of use. These common side effects may include symptoms such as runny nose, gas, itching, headache, dizziness, depression, increased cough, muscle pain or weakness, sleeping problems, and darkening of the palms and/or soles. Additionally, some individuals may experience bone pain or loss of bone mineral density.
The safety profile of PrEP is generally favorable, especially when adherence to the medication regimen is maintained. However, people with substance use disorders, who are disproportionately affected by HIV, require careful management, as medication treatment can improve HIV treatment outcomes in this population. Advances in injectable PrEP formulations, such as long-acting injections administered twice yearly, offer alternative prevention methods that may improve adherence and reduce “pill fatigue” associated with daily oral regimens. These injectable therapies are currently approved primarily for people with undetectable viral loads and have shown promising potential in both treatment and prevention contexts.
Regarding drug interactions, management is crucial, particularly for individuals co-infected with tuberculosis or other conditions requiring multiple medications. For example, rifamycin antibiotics used in tuberculosis treatment can interact with antiretroviral drugs, necessitating careful monitoring and adjustment of therapy. In the broader context of HIV prevention and treatment, understanding and managing these interactions ensures safety and maintains efficacy.

Impact and Effectiveness

Substance use disorders and other social determinants disproportionately affect people living with HIV, contributing to disparities in health outcomes. Medication treatments, including pre-exposure prophylaxis (PrEP), have significantly improved HIV prevention and treatment outcomes, especially when adherence is maintained. Despite these advances, HIV continues to disproportionately impact certain populations in the United States, such as Black and Hispanic communities, men who have sex with men (MSM), transgender individuals, and people who use illicit drugs.
Oral PrEP, primarily consisting of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), has been shown to be highly effective in preventing HIV infection, with efficacy rates up to 86% in studies involving MSM and serodiscordant heterosexual couples when

Social and Cultural Considerations

Social and cultural factors play a critical role in the uptake and adherence to HIV prevention methods such as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP). Stigma remains one of the most significant barriers affecting individuals at risk for HIV, especially among marginalized groups. For example, women who engage in sex work in Sub-Saharan Africa face stigma and structural challenges—including transportation difficulties and healthcare access barriers—that reduce PrEP uptake despite high HIV prevalence rates in this population. Similarly, disparities in PrEP access persist across gender and racial lines, with males and White populations more likely to receive PrEP compared to females and Black or Hispanic populations, highlighting systemic inequities in healthcare delivery.
Internalized or self-stigma further exacerbates these challenges by negatively impacting individuals’ self-worth and willingness to engage in prevention or treatment programs. Patients who internalize societal stigma around HIV may experience shame, guilt, and social isolation, which can reduce treatment adherence and engagement with healthcare services. Addressing self-stigma is therefore essential in improving health outcomes for people living with or at risk of HIV.
Culturally competent care and tailored health communication are necessary to mitigate these social barriers. For instance, training healthcare workers to provide gender-affirming care, including using chosen names and pronouns, has been shown to improve viral suppression and communication among transgender patients living with HIV. Furthermore, incorporating patient feedback into service delivery can enhance support for disclosure and adherence strategies, such as planning for travel or medication schedules, thus encouraging sustained use of PrEP among at-risk populations.
Disparities in HIV prevention efforts remain a concern in the United States, where the epidemic disproportionately affects Black and Hispanic communities, men who have sex with men, transgender individuals, and people who use illicit drugs. National strategies emphasize increasing awareness and knowledge of HIV prevention tools like nonoccupational PEP (nPEP) and improving access and adherence to these interventions as core components to reduce new infections. A person-centered approach that respects individual choices while considering the influence of social, economic, and political contexts is fundamental to these efforts.

Future Directions and Research

Research into preventative HIV treatments continues to advance, with significant focus on developing long-acting injectable therapies that improve adherence and expand options for people at risk of HIV infection as well as those living with HIV. At CROI 2023, Professor Joseph Eron highlighted new drugs such as lenacapavir—a subcutaneous injection administered every six months—offering the longest-acting pre-exposure prophylaxis (PrEP) currently available, which may simplify treatment regimens and enhance patient compliance compared to daily oral medications.
In addition to lenacapavir, broadly neutralizing antibodies (bnAbs) are being explored for their potential role in both treatment and prevention, representing promising avenues for future HIV management. These advancements could particularly benefit individuals experiencing “pill fatigue” by providing alternatives to daily oral therapies, which remain the standard for many patients.
Despite these promising developments, challenges persist in ensuring equitable access to these novel therapies. Current injectable options are approved primarily for individuals who have achieved viral suppression (“undetectable” status), limiting their availability to a broader population. Expanding eligibility criteria and healthcare infrastructure, especially in underserved regions such as the southern United States and rural areas, remain critical goals to overcome workforce shortages and enhance treatment capacity.
Addressing disparities in HIV prevention is also a priority, with emphasis on improving PrEP uptake among disproportionately affected demographic groups, including Black and Hispanic/Latinx communities. National initiatives like the Ending the HIV Epidemic (EHE) program have set ambitious targets to reduce new HIV diagnoses by 2030, underscoring the need for comprehensive strategies that increase PrEP awareness, access, and adherence.
Moreover, integrating a multidisciplinary healthcare workforce—comprising nurses, pharmacists, behavioral health specialists, and advanced practice providers—can further expand patient access and support adherence to preventive therapies. Research efforts continue to explore optimized treatment protocols and community-based interventions aimed at destigmatization, education, and enhanced testing programs, which are essential components in reducing the HIV epidemic on a national scale.

The content is provided by Jordan Fields, Scopewires