Acceptability of a long‐acting injectable HIV prevention product among US and African women: findings from a phase 2 clinical Trial (HPTN 076)

Abstract

IntroductionHigh HIV incidence and low adherence to daily oral PrEP among women underscore the need for more acceptable and easier to use HIV prevention products. Global demand for injectable contraception suggests that new, long‐acting, injectable formulations could meet this need. We examine acceptability of a long‐acting injectable PrEP among HIV‐uninfected women in Zimbabwe, South Africa and two United States phase 2 trial sites.MethodsQuantitative surveys were administered at the first, fourth and sixth injection visits. Focus group discussions (FGD) were conducted after the sixth injection visit. We compared the acceptability of injectable product attributes, prevention preferences and future interest in injectable PrEP by site and arm and ran longitudinal ordinal logistic regression models to identify determinants of future interest in injectable PrEP.ResultsBetween April 2015 and February 2017, the trial enrolled 136 (100 African, 36 US) women with a median age of 31 years. Most participants (>75%) rated injectable attributes as very acceptable. While few reported rash or other side effects, 56% to 67% reported injection pain, with nonsignificant differences over time and between arms. During FGDs, participants described initial fear of the injectable and variable experiences with pain. Most US and African participants preferred injectable PrEP to daily oral pills (56% to 96% vs. 4% to 25%). Future interest in using injectable PrEP was associated with acceptability of product attributes and was higher in African than US sites. In FGDs, participants described multiple reasons for trial participation, including a combination of monetary, health‐related and altruistic motivations. While associated with future interest in use in univariate models, neither altruistic nor personal motivations remained significant in the multivariate model.ConclusionsThis study found that long‐acting injectable PrEP is acceptable among African and US women experiencing product use. Acceptability of product attributes better predicted future interest in injectable use than experience of pain. This is reassuring as a single‐dose regimen of a different product has advanced to phase 3 trials. Finally, the study suggests that future demand for an injectable PrEP by women may be greater in African than US settings, where the risk of HIV is highest.

Acceptability of Long-Acting Injectable Cabotegravir (CAB LA) in HIV-Uninfected Individuals: HPTN 077

“…Over the injection phase of the trial, 27 participants permanently discontinued injectable product use. Stated reasons for discontinuation included product-related side effects, inability or unwillingness to follow study procedures, abnormal lab values, reactive HIV tests, and desire for pregnancy or to terminate the study [ 20 ]. In a supplemental analysis, we found a significant inverse association between participants’ perceived acceptability of pain and discontinuation; participants with higher acceptability of pain had a lower risk for discontinuation.…”

“…Both FIIP and ever use of injectable contraception were particularly high among females in non-U.S. settings, findings which were also reflected in phase 2 trial of RPV LA [ 20 ]. In several past HIV prevention trials of oral or topical products among African females, low adherence has been attributed to low HIV risk perception, females’ concerns about stigma, and challenges disclosing to partners compounded by the need to use a product daily [ 29 – 32 ].…”

“…To date, two different LAI-PrEP products (TMC278/rilpivirine [RPV LA] and GSK1265744/cabotegravir [CAB LA]) have been evaluated for safety and acceptability. Although RPV LA was found to be safe, generally well tolerated and acceptable to a cohort of African and U.S. women, the product is not currently being advanced for further evaluation as a prevention option, in part due to the need for cold chain storage and concerns about resistance [ 19 , 20 ]. CAB LA is currently being evaluated in phase 3 trials after being first evaluated for safety, tolerability, and pharmacokinetics (PK) among U.S. men in the ECLAIR trial [ 21 ] and subsequently among HIV-uninfected, low-risk males and females in South Africa, Malawi, Brazil and the U.S. in HPTN 077 [ 22 ].…”

“It’s hard for us men to go to the clinic. We naturally have a fear of hospitals.” Men’s risk perceptions, experiences and program preferences for PrEP: A mixed methods study in Eswatini

“…MSW's recommendations for PrEP education in places where men congregate and PrEP delivery through key people (chiefs, councilors, local health workers) or key institutions (schools, workplaces) would have to be trialed to determine appropriateness regarding regular HIV-testing and confidentiality. MSW's preference for less frequent PrEP such as injectables has also been depicted in women-focused studies as aiding adherence [54,55], while on-demand oral PrEP has so far been trialed and proved effective for MSM [56], yet could also widen MSW's PrEP choices. MSW further suggested to include more counselling and client follow-up to motivate men to stay engaged with PrEP.…”

An open‐label, randomized crossover study to evaluate the acceptability and preference for contraceptive options in female adolescents, 15 to 19 years of age in Cape Town, as a proxy for HIV prevention methods (UChoose)

“…Previous studies, mostly done in adult women have suggested that delivery in a long-lasting injection would be a good target for drug development [15][16][17][18]. However, given the distinct developmental, physical and social differences between adult women and female adolescents [19], it is essential to explore how the mode of delivery of an HIV prevention option impacts acceptability and use in the adolescent population.…”