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PrEP Promise

CE / CME

PrEP: Fulfilling the Promise of Current and Future Regimens

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

CME/CE Information

Activity

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Course Completed

Currently, I am aware of the potential for emerging HIV PrEP modalities to address health disparities that present barriers to wider uptake of PrEP.

Can the Next Generation of PrEP Modalities Address PrEP Barriers?

The next generation of PrEP modalities offers potentially exciting benefits. The first variation beyond once-daily dosing of oral PrEP was the on-demand 2:1:1 regimen, which is recommended only for cisgender men because of a lack of clinical evidence for cisgender women.7 Less frequently dosed modalities like this are very important because there are individuals who just cannot or do not want to do something daily and desire a longer dosing interval.

In some settings, the DPV vaginal ring is another PrEP option, which allows cisgender women an option for a longer dosing interval.41 It has little systemic absorption, hence fewer systemic adverse events.

The most recent emerging PrEP option is the LA injectable, such as the integrase inhibitor CAB. 41 People who want to get their prevention, walk out the door, and not think about it for 2 months will benefit from this modality. It is important, however, to return every 8 weeks for another shot to be protected.

As we think about service delivery models, we also should think about the kinds of products that may have a bearing on the service delivery model that can be used. For example, mail-order or home delivery may help increase uptake but may be more suitable for oral PrEP or the DPV ring than for LA CAB.

LA CAB presents unique challenges, because a trained individual must administer the injection. However, there are ways to improve access by having injection clinics dedicated to maintenance dose injections.

Other delivery systems are in advanced stages of development, including subdermal implants,42 inserts for either vaginal or rectal use,43 and other ring combinations.

Lenacapavir is a novel parenterally administered HIV-1 capsid inhibitor in development both for PrEP and treatment.44 It has a prolonged half-life and needs to be administered as an SC injection only every 6 months. It appears to be safe and highly effective, working against both wild-type and multidrug-resistant HIV.

An advantage of lenacapavir for PrEP is its unique mechanism of action and the fact that it can be administered subcutaneously, raising the possibility of self-administration.

Results are expected in the next year or two from 2 large phase III trials (PURPOSE-1 and PURPOSE-2) evaluating lenacapavir for HIV prevention among men who have sex with men, nonbinary individuals, transgender individuals, and cisgender women in several countries (NCT04994509, NCT04925752).

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Global Barriers to Implementation of Injectable PrEP

With these new and emerging PrEP modalities, it is important to ensure that they truly increase access and reduce disparities in PrEP uptake, rather than simply providing alternatives for individuals already engaged in an oral PrEP program. The rapid development of implementation science to guide the large-scale adoption of LA PrEP will be important to understand the outstanding issues and implementation approaches for populations who urgently need effective prevention choices. Approval is not enough without effective and equitable implementation. To address this, several LA CAB implementation projects are planned around the globe.45

Although injectable PrEP obviates the need for the potentially stigmatizing adherence behavior of taking a daily pill, it is important to ensure that patients receive their injections on time. A steady supply chain and logistics for distribution are needed to ensure this.

Delays in HIV Diagnoses With PrEP

With LA PrEP, breakthrough infections are very rare, but still unexplained.46

One reason for breakthrough infections may be that, in individuals who were acutely infected at initiation, LA products may delay seroconversion and impede the detection of HIV antibody emergence. This has led to the recommendation for antigen-based testing prior to commencing LA injectable PrEP.

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Challenges with PrEP Monitoring

CDC guidelines recommend molecular testing to guide PrEP implementation, but this is not feasible or affordable for low- and middle-income countries. Implementation studies will be key for us to understand what is best and feasible.7

Modeling studies of LA CAB PrEP have suggested that, despite the potential for integrase inhibitor resistance with breakthrough infections, it is likely that the reduction in HIV incidence and HIV-related mortality will outweigh these risks.16,46 The lack of molecular testing should not keep us from using LA CAB PrEP in low- and middle-income countries. This also will need to be monitored in real-world studies.

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Conclusions

Efforts are being made to help enable access in the least-developed, low-income, low-middle‒income, and sub-Saharan African countries. Through an agreement, 3 generic manufacturers will have the opportunity to develop, manufacture, and supply generic versions of LA CAB for PrEP in 90 countries, subject to regulatory approvals.

There are concerns, however, about how long this will take given the complexity, so there are also calls for technology transfer to expedite manufacturing capability. With current availability, there are still far too many people left behind, including those who stand to benefit the most from this scientific advancement of LA PrEP.

Inequalities are a major driver of the HIV epidemic, which continues to disproportionately burden vulnerable populations despite the availability of effective prevention. Our current models of HIV prevention delivery do not respond to the needs of these populations.

The most vulnerable populations struggling with poverty and social inequalities are the ones who suffer the most from HIV. We must ensure that novel PrEP strategies do not deepen the already profound inequalities. On the contrary, we must ensure that, with these new PrEP options, no one is left behind.

The future for HIV prevention is bright, but not guaranteed.

After participating in this activity, I am aware of the potential for emerging HIV PrEP modalities to address health disparities that present barriers to wider uptake of PrEP.

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