Long-Acting PrEP, HIV Vaccines are Key Focus Areas for Optimizing Prevention


National Institutes of Health experts discuss optimization of existing strategies for HIV treatment and prevention, as well as the development of new approaches.

To help eliminate HIV, new treatment and prevention strategies are needed to improve efficacy and uptake across diverse communities, National Institutes of Health experts wrote in a commentary in Clinical Infectious Diseases.

In the commentary, the authors discussed how existing strategies can be optimized and outlined the potential of novel interventions for the future.

Although effective strategies that include the use of antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) should, theoretically, end the HIV pandemic, there are many challenges that persist. Despite the benefits of ART, uptake remains suboptimal due to adherence challenges, including those related to substance abuse, housing deficits, pill fatigue, drug toxicity, stigma, and discrimination, according to the authors.

Gaps are prevalent in all stages of treatment and prevention; however, the authors wrote that optimizing the current HIV treatment and prevention toolkits with improved implementation strategies can help bridge these gaps.

One way to do this would be to achieve durable control of the virus without the need for daily ART. Potential approaches include long-acting ART and broadly neutralizing antibodies (bNAbs) administered at intervals of several months. Other strategies that take aim at curing the disease include stem cell transplantation and gene editing approaches.

According to the authors, the optimization of HIV prevention “will require innovative approaches in 2 key areas: PrEP and vaccines.”

Long-Acting PrEP

To optimize PrEP, novel strategies under investigation include short- and long-acting oral pills, long-acting injectables and implants, monoclonal antibodies, topically applied products for rectal and vaginal use, and multi-purpose tools for HIV prevention and contraception.

Additionally, ART and BNABs are both being studied as long-acting PrEP, the authors noted. They cited trials investigating novel ways to optimize ART for PrEP, such as long-acting injectable cabotegravir compared with oral Truvada and an implant of a novel reverse transcriptase-translocation inhibitor, MK-8591.

Developing long-acting bNAbs is another approach for achieving long-acting PrEP. Currently, 2 clinical studies are evaluating passive transfer of VRC01 monoclonal antibody in high-risk men and women around the world.

“The successful outcome of these clinical trials would prove the concept that the bNAb could be a safe and effective intervention to prevent HIV acquisition among high risk individuals,” they wrote.

HIV Vaccines

According to the authors, there are multiple approaches to an HIV vaccine that are in various stages of pre-clinical and early clinical development. They named 2 key strategies that have progressed to advanced clinical trials: the empiric or inductive approach to testing vaccine candidates in order to identify and optimize the correlate of immunity and the deductive approach of assuming a correlate of immunity and then designing vaccine candidates that can induce that specific correlate.

“While these various approaches and strategies to develop an HIV vaccine are being actively pursued and optimized, the question remains how effective an HIV vaccine should be to have a major impact on the HIV epidemic,” the authors wrote.

In all, the authors concluded that it is necessary to maximally implement existing interventions as we continue to pursue innovative approaches and interventions for preventing and controlling HIV.


Eisinger RW, Folkers GK, Fauci AS. Ending the HIV Pandemic: Optimizing the Prevention and Treatment Toolkits. Clinical Infectious Diseases. 2019. https://bit.ly/341nL05. Accessed October 24, 2019.

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