An ounce of prevention is worth a pound of cure. Questions remain though in the field of HIV prevention on how best to deliver that ounce. The use of HIV pre-exposure prophylaxis (PrEP) is a way for people to prevent HIV infection. A daily oral PrEP pill is effective at reducing the risk of HIV infection among men who have sex with men (Grant et al., 2010) and among couples where only one partner is HIV-positive (Baeten et al., 2012). However, PrEP administered by pill, vaginal gel or ring products among women, many in sub-Saharan Africa, shows no (Marrazzo et al., 2015) or more modest (Baeten et al., 2016) effectiveness. The difference? It comes down to adherence, meaning it only works if people consistently take PrEP according to the prescribed schedule.
One way to eliminate the need for daily PrEP adherence is to make a drug that stays in the system and works over a longer period. These “long acting” drugs are often delivered through an injection. The safety and acceptability of a long-acting injectable drug was tested in the HPTN 077 phase 2a clinical trial. As part of the trial, my colleagues and I conducted a study to explore if participants would actually find a long-acting injectable PrEP product desirable and acceptable (Tolley et al., 2020). Our findings are important for researchers and program implementers planning to introduce or design such injectable products, and I describe several key takeaways here.
About HPTN 077 and our study
The HPTN 077 trial evaluated the safety, tolerability and acceptability of a long-acting injectable HIV prevention drug called cabotegravir. By acceptability we mean, “Are people willing to use the product if they desire protection from HIV?” and “Would they use this product if other options were also available?”
The trial enrolled a total of 199 men and women from Brazil, Malawi, South Africa and the United States (U.S.) who were randomized to receive either cabotegravir or placebo injections administered through two shots every 12 weeks (cohort one) or through one larger shot given every eight weeks (cohort two). Because the trial included both men and women, was located at sites in the U.S., South America and Africa, and evaluated two different dosing regimens, it provided a unique opportunity to understand how acceptability and future demand for a long-acting injectable PrEP product might vary by gender, geography and/or dosing strategy.
In our study, we conducted a baseline questionnaire to examine participants’ motivations for joining the trial, their past experiences with contraceptive or other injections, and their perceived HIV-related risks and product preferences. We conducted follow-up acceptability surveys one week after the first, second and third injection in both cohorts, as well as after the fourth and fifth injection for cohort two. We asked participants in follow-up surveys how acceptable they found a range of product attributes, experiences of pain and other side effects. In the last follow-up survey in each cohort, we asked participants to indicate their level of interest in using an injectable PrEP product if available post-trial.
An interesting aside is that we originally developed our acceptability questionnaires for a separate phase 2 trial of a different injectable PrEP product (rilpivirine) which was evaluated in African women, HPTN 076 (Tolley et al., 2019). When we use similar questionnaires in different studies, it makes it possible to compare findings across different products and populations.
Takeaways for researchers and implementers
Acceptability is high overall
Interest equals acceptability
Experience with injectable contraception influences interest
There is still much we must learn after the HPTN 077 trial. Some of it is clinical. For example, does this injectable PrEP product work for women as it has been shown to work for men? But there is also much we can learn that is more sociocultural or behavioral. For example, will women continue to use an injectable product over a period of years and what aspects of the product will they find most or least acceptable? What aspects of the product, the user and his/her context will generate the willingness – or even desire to use the product beyond a clinical trial setting? Ultimately, we need to develop and deliver products that are not just effective but also desirable if we are going to replace a pound of cure (antiretroviral treatment) with an ounce of prevention (PrEP).
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