CE / CME
Nurses: 0.75 Nursing contact hour
Physicians: maximum of 0.75 AMA PRA Category 1 Credit™
Pharmacists: 0.75 contact hour (0.075 CEUs)
Released: November 20, 2023
Expiration: November 19, 2024
Introduction
Since the FDA approval of the first oral option for pre-exposure prophylaxis (PrEP) more than a decade ago, additional options for daily, event-driven, and long-acting (LA) use have been studied and made available in certain settings and populations, and a countless number of HIV infections have been prevented. The current PrEP landscape now puts prevention in the hands of the individual. With consistent use, PrEP is estimated to be 99% effective at preventing HIV acquisition from sexual transmission.
Initially, our options for prevention were limited to ABC—abstain from sex, be faithful to a single partner whose status you know, or condomize—and very much in that context, it was all about male condoms. This left out a large proportion of people who are at risk of HIV acquisition, because it is not always possible for young women to request that a male latex condom be used to ensure safer sex.
PrEP puts prevention and safer sex in the hands of the individual. Young women can take back their own sexual destiny and can be in control of the outcomes of their sexual lives in terms of risk of HIV acquisition. PrEP provides a discreet, user-controlled method to prevent HIV.
UNAIDS 95-95-95 Goals
One of the most powerful ways to prevent HIV is when someone living with HIV starts antiretroviral treatment and their virus becomes undetectable as per laboratory measurement.1 Then that individual cannot sexually transmit the virus to their partner because undetectable = untransmittable (U=U). This is known as “treatment as prevention” and is an indirect way of preventing HIV.
Progress toward the UNAIDS 95-95-95 goals gives us insight into the impact of treatment as prevention on the avoidance of new HIV infections. The 95-95-95 goals are that globally by 2030, 95% of people living with HIV will know their status, 95% of those who know their status will be receiving treatment, and 95% of those receiving treatment will have suppressed HIV-1 RNA.2
Progress toward the 95-95-95 goals has been made in certain countries and regions, but much of the world is falling short of these targets.3
This is where PrEP comes in. Unlike the indirect approach of treatment as prevention, PrEP means an individual can directly exert the control themselves.
PrEP is therefore another important biomedical intervention when it comes to HIV prevention, and it also must be scaled up worldwide to realize global HIV control.
Successful HIV Prevention Program
Between 2010 and 2022 in Sydney, Australia, there was a 56% decline in HIV diagnoses statewide, but when looking at the data in inner Sydney, where most gay and bisexual men seek care, there was an 88% decline in HIV diagnoses over that period—which is an extraordinary decline.3
There was really great treatment progress over that period toward the UNAIDS 95-95-95 goals, and there was enormous PrEP uptake, as well. New South Wales did not roll out PrEP until 2016, but once they started, they did it quickly and at scale so that by 2022, approximately 80% of at-risk gay and bisexual men in inner Sydney were taking PrEP—which is extraordinarily high coverage—and they were able to reap the benefit in terms of reductions in new infections.3
What lessons can we learn from inner Sydney? The success came from treatment as prevention and from PrEP, along with a background of condom use, stigma reduction, and other sexual health services.
Contributors to this success include strong community organizations that are funded by the government and that promoted PrEP widely, consistent government support for evidence-based HIV prevention programs, and a public healthcare system where most everybody can afford to see a doctor, afford the drugs, and afford the pathology testing.
Summary of PrEP Options
This table lists the available PrEP options in each column, along with current FDA approvals and guideline recommendations for each relevant group.4-10
PrEP for Cisgender Men
For some, the advent of PrEP has revolutionized their sexual experiences. Take, for example, cisgender men who have sex with men who lived through the beginning of the epidemic with background fears of acquiring HIV. Despite their best efforts at prevention, some had underlying concerns about condoms failing and anxiety around HIV tests.
As shown in the figure, there are now several PrEP regimens available—including 1 pill once-daily, LA injectable, and on-demand options—that have changed the level of fear and anxiety.
Daily oral FTC/TDF and daily oral FTC/TAF are the 1 pill once-daily options for cisgender men and transgender women. FTC/TAF is an alternative to FTC/TDF; it has bone- and renal toxicity‒sparing effects and could be considered for older individuals or people who have renal issues.4-8,11
Oral FTC/TDF on demand and injectable CAB Q2M are nondaily PrEP options for cisgender men. Oral FTC/TAF is not recommended for on-demand dosing, as it has not been studied.4-8,11
Event-Driven PrEP
Event-driven PrEP is an alternative to daily oral PrEP for both men (including men who have sex with men) and transgender women. In the field of prevention, it is important for people to have many different options to maximize uptake. PrEP and condoms are key components of the prevention toolbox.
A benefit of on-demand PrEP is that it may fit the sexual behavior of some individuals better than daily PrEP. For people who have infrequent sex, by using on-demand PrEP, they actually would need fewer pills than if they were taking a daily regimen. For someone having sex once per week, this would mean a total of 4 pills per week instead of the 7 that would be taken with daily dosing. If sex were intermittent, this would mean there are periods when PrEP does not need to be taken at all.
On-demand PrEP means taking it only around the time of a sexual encounter. It also is referred to as 2-1-1 dosing. Two pills are taken 2-24 hours before sex, 1 pill is taken 24 hours after the first dose, and 1 pill is taken 48 hours after the first dose.7
So, what lessons were learned from the studies of on-demand PrEP?
Researchers started to think about on-demand PrEP more than 10 years ago because they thought it would be difficult to get people who are otherwise healthy to take a daily pill. The idea that adherence might be better with on-demand PrEP vs daily pills set the stage for the placebo-controlled ANRS IPERGAY study, which compared on-demand dosing of FTC/TDF PrEP with placebo in men who have sex with men in France and in Canada. The results of this trial were beyond researchers’ expectations, with an 86% relative reduction of HIV infection with on-demand FTC/TDF vs placebo during the double-blind phase of the study.12 During the open-label extension phase, the reduction of HIV incidence was 97%.13
PrEP for Cisgender Women
PrEP options for cisgender women are expanding. Currently FDA-approved options include daily FTC/TDF and more recently injectable CAB.4-9 The DPV ring is another option in some low- and middle-income high-burden settings.10
The DPV vaginal ring is a nonnucleoside reverse transcriptase‒infused ring that is comfortably placed within the vagina and replaced every 28 days.14
This wider range of options allows patients to select the PrEP that meets their needs as part of their individualized health regimen. Some may prefer a LA injectable, as that medication does not have to be taken home. Others may prefer an oral option where they can decide when, where, and how to take the medication.
Despite the data for PrEP for women, people often assume that PrEP is still for men who have sex with men or people who are in high-risk populations. Women who take PrEP can be stigmatized as sex workers or individuals engaged in needle-based drug use. There is a need to shift the conversation from PrEP being for people who are most at risk to now being available for everyone who feels they need protection from HIV acquisition.
The Next Generation of PrEP Drugs
The next generation of PrEP drugs will focus largely on the use of LA injectables or extended-use preparations.
LA CAB is a novel integrase strand transfer inhibitor that is administered as a single IM (gluteal) injection every 8 weeks after an initial 1-month loading dose. It is quite a large-volume injection to the muscles of the buttock, which can cause injection-site pain.9
In HPTN 083, CAB was compared with daily oral FTC/TDF in men who have sex with men and transgender women at 43 sites across different regions.15 CAB was shown to reduce the HIV incidence by 66% and met criteria for superiority, a significant result given the high efficacy of FTC/TDF when taken as prescribed.
In HPTN 084, which evaluated cisgender women in Africa, results were even more impressive.16 CAB reduced the HIV incidence by 88% compared with FTC/TDF oral PrEP. This is a major finding for cisgender women, because in previous FTC/TDF PrEP trials, lower efficacy was observed in this population compared with men who have sex with men and transgender women.
These 2 studies led to FDA approval of LA CAB for HIV prevention in December 2021.17 Since then, other countries have approved it for prevention, such as Australia, Zimbabwe, Botswana, Brazil, and South Africa.
Although approved, LA CAB is not necessarily incorporated in public health programs for PrEP because of availability and cost. It is critically needed for us to understand how to efficiently and effectively bring these new PrEP products to people at risk of HIV infection, building on the lessons learned from the oral PrEP scale-up.
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