Breaking Barriers: The Future of HIV Prevention and the Fight for Widespread PrEP Access

HIV/AIDS by Infection Control Today

Why HIV/AIDS Still Matters

What if a 32-year-old man, previously in prime health, suddenly developed a persistent high fever unresponsive to antibiotics? With no cough or abdominal symptoms, his condition worsens, baffling his medical team. They notice purple lesions on his palate. Despite treatment, the man succumbs to Kaposi’s sarcoma due to HIV/AIDS.

Today, this hypothetical case is rare in the US because combination antiretroviral treatment (ART) has transformed HIV/AIDS from a near-ubiquitous death sentence to a chronic disease.Indeed, the estimated 12% decline in new HIV infections (2018 to 2022) and the fact that only an estimated 31,800 new HIV infections were detected in 2022 are positive reminders that a public-private sector partnership has brought the US within sight of ending the HIV epidemic (EHE).^1,2

However, 13% of people living with HIV (PLWH) do not know their status, and among people at high risk of acquiring the virus, preexposure prophylaxis (PrEP) for continuous protection is very low.^1,3 In the absence of a significant scale-up in connecting high-risk individuals to accessible, affordable PrEP, the US risks failing to reach the goal of a 90% decrease in new HIV infections by 2030—1 of the primary goals of the EHE initiative.² Thus, we risk a scenario of disease progression, analogous to the hypothetical case, and thousands of Americans being added to the global HIV-related death toll of more than 42 million at the time of writing.⁴

Table 1: Key Long-Acting Agent Clinical Trials for HIV Preexposure Prophylaxis^28-31

(Credit: Author)

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Who is at risk for HIV?

The US sees higher HIV rates among gay and bisexual men, transgender women, Black/African American and Latin individuals, and people who inject drugs (PWID).⁵ The southern US, which comprises just over a third of the population, accounts for nearly half (49%) of new HIV infections.^1,6 While new HIV diagnoses have dropped nationwide, the Deep South (Alabama, Florida, Georgia, Louisiana, Mississippi, North Carolina, South Carolina, Tennessee, and Texas) still faces a significant challenge. Their diagnosis rate is 65% higher than that of other Southern states (Arkansas, Delaware, Washington DC, Kentucky, Maryland, Oklahoma, Virginia, and West Virginia), which matches the US average of 17 per 100,000 people.⁷

PrEP, a preventive antiretroviral treatment (ART) strategy, coverage is low among African American men who have sex with men (MSM) in the South, affected by stigma, healthcare mistrust, poverty, and misinformation. Additionally, clinic access is scarce in high-poverty areas, and awareness is also low among low-income African American women.⁸ While these challenges have to be addressed, it is also important to note that HIV is not regional and that less than 70% of all PLWH were virologically suppressed in 2022, and only 30% of PrEP-eligible individuals received these medications.⁹ Thus, a substantial proportion of the HIV-positive population still has detectable virus in their blood, which can lead to ongoing transmission and potential health complications.

Is PrEP a Panacea?

Condom usage has contributed to HIV reduction, but not eradication, and is not feasible for those wishing to become pregnant.¹⁰ That is why the US Preventive Services Task Force (USPSTF) strongly recommends PrEP (alongside safe sex practices and continuous HIV care) for HIV prevention, meaning they are very confident it is highly beneficial when taken as prescribed. Health care professionals should offer PrEP to all sexually active adults and adolescents who are at risk of HIV.¹¹

PrEP can prevent HIV infection, reducing the risk by up to 99% from sex and at least 74% from injection drug use. It is recommended for all sexually active adults and adolescents at risk, weighing at least 35 kg (77 lb). Providers should discuss PrEP with all sexually active patients to increase awareness and reduce stigma, and it can be prescribed to any patient who asks for it, regardless of reported HIV risk factors. Any licensed provider can prescribe PrEP, which includes daily oral medications (Emtricitabine/tenofovir disoproxil fumarate [F/TDF], Emtricitabine/tenofovir alafenamide [F/TAF]), and the injectable long-acting cabotegravir (CAB) injected every 2 months for eligible patients (Figure 1).^{1-3, 12,13}

Postexposure prophylaxis (PEP) involves a 28-day regimen of ART to prevent HIV infection after high-risk exposure and must be started as soon as possible.¹⁴ Both strategies are crucial in preventing HIV, but PrEP is a continuous preventive measure, while PEP is an emergency response.

Table 1: Key Long-Acting Agent Clinical Trials for HIV Preexposure Prophylaxis^28-31

(Right Click to open in a new tab.)

(Credit: Author)

While clinical trial differences in effectiveness have been observed among the different PrEP agents, real-world data suggest that this should not be the primary consideration in practice, as all the medications are highly, but not quite 100% effective. Instead, patient preference, safety, convenience, and cost should be considered.¹⁵ Due to biological, social, and cultural factors, women’s uptake of, adherence to, and persistence in the use of PrEP remains limited across the globe. This has led to calls for additional PrEP options.

Experts suggest considering CAB-LA for adults and adolescents of all genders at risk for HIV through sexual routes who cannot tolerate an oral regimen or prefer an injection. Additionally, CAB-LA is not known to affect renal function, making it a safer option for patients with renal issues.¹⁵ This does not negate the need for continued vigilance regarding drug toxicity and resistance.^16,17 However, the convenience of dosing every 2 months with CAB-LA versus daily oral medications may still be challenging for some patients. CAB-LA and F/TAF are also more expensive than F/TDF and may require preauthorization, posing a barrier to care for some patients.¹⁵

Cost remains a barrier for PrEP, with out-of-pocket expenses exceeding $1,000 per year for insured users. Even with available financial assistance, lack of insurance still hinders accessibility.¹⁸ Pending future Supreme Court decisions, help for HIV prevention and treatment can still be found through the Ryan White HIV/AIDS Program (RWHAP) Medical Provider tool, state HIV/AIDS toll-free phone numbers, and the Common Patient Assistance Program Application for low-cost medicines. RWHAP provides a range of core medical and support services, including case management, drug assistance, mental health services, and housing support for eligible individuals diagnosed with HIV or AIDS.^19,20

Boosting PrEP Uptake: What Works?

A syndemic refers to the occurrence of two or more health conditions that cluster within a population and exacerbate each other's effects. Syndemic theory examines how diseases and social problems interact and worsen each other, helping us find better ways to prevent and treat them together.²¹ Consistent with this theory, a recent study examined how gender-based violence (GBV) and post-traumatic stress disorder (PTSD) symptoms affected PrEP use among transgender and nonbinary (TGNB) individuals. It found that GBV predicted failure to start PrEP and PTSD symptoms were linked to stopping PrEP.²²

Conversely, a2018-2021 study in New York City found that integrating PrEP services with sexually transmitted infections (STIs) and other health care services in primary care and women's health clinics substantially increased the percentage of health care professionals prescribing PrEP, from 11.5% to 49%.²³Similarly, an inpatient Addiction Consult Service (ACS) significantly increased PrEP/PEP prescriptions for people who inject drugs (PWID) by leveraging the reachable moment of hospitalization.²⁴

Community engagement programs that empower PWID have shown promise in expanding PrEP access. Engaging community leadership helps address structural barriers and ensures that services are tailored to the needs of high-risk individuals.²⁵ Other innovative approaches have involved crowdsourcing solutions to enhance PrEP access, such as promotional campaigns tailored to community needs.²⁶

Future Directions

Consistently taking ART, as prescribed, can prevent or control HIV, enabling infected patients and their uninfected partners to have near-normal lifespans. However, ART usage must be combined with other factors, eg, safe sexual behaviors, giving PWID access to sterile needles, promoting safe sexual behaviors, supporting routine HIV testing, giving injecting drug users access to sterile needles, and reducing mother-to-child transmission through interventions during pregnancy, childbirth, and lactation. Even when these goals are met, ART carries a lifelong risk of medication resistance, side effects, and increased risk for chronic diseases versus HIV-free individuals. Additionally, access to ART is still restricted in many regions due to infrastructure, stigma, and cost. Instead of requiring lifelong ART, promising long-acting agents used alone or combined with other treatments seek to achieve prolonged viral remission or elimination.²⁷

In December 2021, the US FDA approved CAB-LA. Clinical trials showed CAB-LA to be safe and effective at preventing HIV. Given every 2 months, it offers a discreet, long-lasting option preferred by many at risk of HIV, and a formulation with a 4-month dosing interval is also currently under investigation (Table 1)^28-32 Analysis indicated that generic manufacturers could produce CAB-LA affordably.³³ Another investigational long-acting agent, lenacapavir, showed remarkable efficacy in 2 separate phase 3 trials. Compared to traditional daily oral PrEP, lenacapavir achieved 100% prevention in cisgender women and a 96% HIV prevention rate in cisgender men who have sex with men, transgender men, transgender women, and gender nonbinary individuals.^28,31

Vaginal rings with tenofovir or dapivirine, lasting over 3 months and possibly including birth control, are in early development. A 1-month dapivirine ring has not been FDA-approved despite WHO's recommendation. Long-acting antibodies given by IV or injection are being developed for HIV prevention, and another preventive agent, MK-8527, is in development as a monthly pill.³⁴

Long-acting HIV PrEP can significantly enhance prevention efforts by addressing some of the challenges associated with daily ART. These agents, such as lenacapavir and cabotegravir, can reduce the need for frequent dosing and clinic visits, improving adherence and minimizing stigma. By offering extended protection with fewer side effects and lower risk of resistance compared to approved oral PrEP, long-acting PrEP can make HIV prevention more accessible and sustainable, especially in high-risk populations where logistical issues and stigma are prevalent.

References

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