Pills, injections, rings or implants? PrEP formulation preferences of PrEP-experienced African women for HIV prevention

Background

In sub-Saharan Africa, adolescent girls and young women (AGYW; aged 15-24 years) have a much higher HIV incidence than their male counterparts[1,2]. Several factors put AGYW at increased HIV risk, including lack of knowledge on safer sexual practices, inability to negotiate male condom use, and various sociocultural practices[2,3].

Oral pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine (TDF/FTC) is highly effective and safe when used consistently[4,5]. Several studies have reported high interest in PrEP among African AGYW, but persistence was low in clinical trials[6,7]. More recently, implementation studies have piloted methods to support young women to adhere (e.g., frequent visits, integration of PrEP into existing sexual and reproductive health services[8-11]), yet adherence to a daily pill remains challenging. Alternate HIV prevention methods that do not need daily adherence could appeal to young women.

Young women have limited biomedical options for HIV prevention. Currently, the only US Food and Drug Administration-approved biomedical prevention method is oral PrEP. Other methods (e.g., the vaginal ring, injections, implants, multipurpose prevention products) are at various stages of regulatory approval or development and should be available in the near future[12]. Recently, the dapivirine vaginal ring received a positive opinion from the European Medical Agency[13]; injectable cabotegravir demonstrated superiority compared to oral TDF/FTC among men who have sex with men, transgender women and cis-gender women[14,15]; and the islatravir implant demonstrated safety and potential to be used annually[16]. However, data is limited on whether these novel HIV prevention methods would appeal to AGYW, especially those who have experienced challenges with daily oral PrEP.

We therefore explored preferences of the current and anticipated PrEP formulations among young women with experience taking oral PrEP.

Methods

Study design and setting:

We conducted a cross-sectional survey among a convenience sample of young women exiting the MPYA (Monitoring PrEP for Young Adult women; NCT02915367) Study after two years of follow-up. This randomized controlled trial evaluated the impact of SMS reminders to support PrEP adherence among young women in Thika and Kisumu, Kenya. MPYA enrolled women aged 18-24 at high HIV risk based on being in a serodiscordant relationships or a VOICE risk score ≥5, which was associated with an HIV incidence >5/100 persons-years[17]. MPYA followed participants quarterly and measured PrEP adherence with a real-time electronic monitor (Wisepill) and pharmacy refill. Overall adherence was low with only 22.3% taking ≥5 doses per week at six months, which did not differ by study arms[18].

Data Collection:

An exit questionnaire was introduced mid-way during study implementation. Preferences were assessed with questions such as, “If all these methods (vaginal ring, injection [such as contraception Depo provera], implants [such as Norplant], oral pills) were available, which one would you prefer? Rank in order of preference with 1 being the most preferred.” These questions were administered face-to-face by MPYA study counselors.

Data Analysis:

Data were analyzed descriptively and associations between variables and PrEP formulation preferences at exit questionnaire completion were assessed using Fisher’s exact test and Wilcoxon ranksum tests. Owing to multiple comparisons, we considered a Bonferroni correction (p<0.005).

Ethics:

The study was approved by the Kenya Medical Research Institute, Mass General Brigham, and the University of Washington Human Subjects Division. All participants provided written informed consent.

Results

Overall, 164/350 (48.6%) of the MPYA study cohort completed the questionnaire; no participants offered the questionnaire declined to answer it. Median age at screening was 21 (interquartile range [IQR] 19, 22). Five participants (3.1%) were married, 90 (54.9%) were single with steady partner, 67 (40.8%) were single with a non-steady partner, and 1 (0.6%) was divorced/separated. The median VOICE HIV risk score was 7 (IQR 6, 7). Among 58 women using hormonal contraception at enrollment, 26 (44.8%) were using injectables, 28 (48.3%) implants, and 4 (6.9%) oral pills.

Among all participants completing the questionnaire, reported preferences for PrEP formulations were: injectables- 59 (36.0%), oral pills- 56 (34.2%), implants- 36 (22.0%), and vaginal rings- 24 (14.6%) (Figure 1). We found no significant associations between preferred PrEP formulation and age, HIV risk score, marital status, contraceptive method, pregnancy intentions, partner knowing PrEP use, employment status, time to get to clinic, or study site (Supplemental table 1). Further, these variables did not differ significantly between the participants completing the exit interview versus those who did not. Participants expressed interest in learning more about HIV prevention methods in the pipeline as follows: injectables - 96 (58.5%), vaginal rings - 91 (55.5%), and implants- 69 (42.1%).

Figure 1: Ranking of Preferred HIV Prevention method.

*The “1st” indicates the most preferable, while the “4th” indicates the least preferable.

Discussion

After being on oral PrEP for up to two years, only one-third of women would prefer the oral formulation if other formulations were available. This finding may partially explain the suboptimal PrEP persistence rates observed in the MPYA Study and similar research[6,7,18]. Among the four currently and potentially available formulations, no single method dominated interest, though injectable methods were the most preferred as has been reported in recent studies[19,20,21]. These findings demonstrate that both systemic and local acting products would have a place in the prevention arena. Moving HIV prevention forward will require several PrEP options, because no single formulation will meet the needs of all young women all the time. Similar experience has been seen with contraception, where other methods beyond oral pills (i.e., injectables, implants, vaginal rings) are also preferred by women[22].

Although, similar formulation options are available locally for contraception (aside from the vaginal ring), women only had experience with oral PrEP, thus limiting the extent of knowledge informing their responses. The young women interviewed also expressed an interest in learning more about these other methods of HIV prevention. There is therefore a need to inform policymakers, health providers, and women about these methods to ease uptake once they become available.

Modelling studies have shown that several HIV prevention options used in combination to cater for individual preferences will be needed to impact HIV incidence, especially among populations at increased risk[23,24]. We therefore need to accelerate the development of other PrEP formulations currently in the pipeline to cater for varying preferences. Such options may translate to increased uptake and persistence in this population, which could have an impact on HIV incidence globally.