Integrated PrEP and STI Services for Transgender Women in Uganda: Qualitative Findings from a Randomized Trial

Abstract

Tenofovir alafenamide fumarate (F/TAF) pre-exposure prophylaxis (PrEP) is understudied in sub-Saharan Africa. The Tandika PrEP study was a randomized trial that evaluated same-day F/TAF initiation, the impact of drug-level feedback on PrEP adherence, and integrated PrEP and sexually transmitted infection (STI) services for HIV-negative transgender women (TGW) in Uganda (NCT04491422). From April 2022-February 2023, a qualitative sub-study of 30 in-depth interviews explored (1) perspectives on same-day initiation of F/TAF PrEP, (2) experiences of urine tenofovir testing and drug-level feedback, and (3) descriptions of self-collection of samples for STI testing. Qualitative data were analyzed using an inductive content analytic approach. Integrated PrEP/STI services were valued by TGW because the convenience of urine testing motivated adherence and allowed for tenofovir and STI detection. (1) Preferred characteristics: F/TAF-based PrEP was easy to take and not readily identifiable as an HIV-related medication, resulting in less stigma than the better-known tenofovir disoproxil fumarate (F/TDF). Weight gain associated with F/TAF use was viewed positively by TGW as a symbol of health and prosperity in African settings. (2) Adherence motivation: PrEP adherence was motivated by a desire not to disappoint healthcare workers; TGW reciprocated adherence support and drug-level feedback by taking PrEP. (3) Facilitating adherence and STI care: Urine testing enhanced STI detection and treatment. Utilization of urine for tenofovir and STI testing motivated the uptake of HIV/STI care, emphasizing the importance of integrated PrEP and STI services. Integrating PrEP/STI services into differentiated delivery models could increase prevention uptake in this vulnerable population.

Introduction

The Joint United Nations Program on HIV/AIDS (UNAIDS) reports that transgender women (TGW) who were assigned male sex at birth but identified as female are at a significantly higher risk of acquiring HIV, with a 14-fold increase in risk compared to the general population [1]. Globally, TGW have an HIV prevalence of 19.9%, with odds of acquisition 66 times higher compared to all individuals aged 15 years or older [2]. Research from sub-Saharan Africa has revealed even higher rates of HIV among TGW than among men who engage in sex with other men (MSM), with six times higher incidence in South Africa and five times higher in Kenya compared to cisgender MSM [3–6]. These findings stress the critical importance of addressing the unique needs and vulnerabilities of TGW, who are considered a high-burden population for HIV [7, 8].

Emtricitabine/tenofovir alafenamide fumarate (F/TAF; Descovy) and emtricitabine/tenofovir disoproxil fumarate (F/TDF; Truvada) are daily oral regimens approved by the United States Food and Drug Administration for HIV pre-exposure prophylaxis (PrEP) [9]. Prior research has indicated that F/TAF has similar efficacy and a better safety profile than F/TDF [10]. In the DISCOVER trial, the efficacy of TAF was non-inferior to F/TDF in decreasing HIV acquisition risk among cisgender MSM and TGW in Europe and North America (incidence rate ratio for F/TAF versus F/TDF 0.47; 95% CI: 0.19–1.15) [11]. Both drugs demonstrated good tolerability; however, TAF showed significantly superior bone and renal safety outcomes compared to F/TDF [11]. Both drugs are commonly used in HIV prevention and treatment worldwide, but due to cost constraints, F/TDF is more widely used in sub-Saharan Africa [12]. For example, Uganda uses TDF-based regimens for antiretroviral therapy (ART) and PrEP [13]. As a result, individuals using PrEP, such as TGW, may prefer to use F/TAF to avoid the potential stigma of being mistakenly identified as living with HIV by using F/TDF [14]. Despite these potential benefits of F/TAF, there is limited research on the usage and experiences of F/TAF-based PrEP in sub-Saharan Africa [15].

PrEP choice may have important implications for adherence, the primary determinant of PrEP effectiveness [16]. However, studies have revealed that adherence to PrEP is often low, including among TGW in Uganda [17, 18]. Incorporating drug-level monitoring and providing counseling and feedback on adherence could be effective strategies for promoting adherence among TGW using PrEP [19–21]. Limited research has been conducted on the impact of drug-level feedback in Sub-Saharan Africa, specifically among TGW taking F/TAF-based PrEP. However, a point-of-care tenofovir (POC TFV) urine test can assess PrEP adherence within four days [22–25]. POC test results are obtainable within five minutes at less than $2 per test, making it a viable option for monitoring PrEP usage in low-resource environments [22]. To our knowledge, no published qualitative studies have evaluated how POC urine TFV testing with drug-level feedback could motivate the use of F/TAF-based PrEP by African TGW.

Additionally, motivation for PrEP use could be influenced by the availability of STI testing. Although routinely integrated into PrEP delivery in high-income settings, syndromic management is standard-of-care (SOC) in many low- and middle-income settings due to the cost and availability of services [26]. The value of this integration has not been explored for TGW. Within a randomized trial designed to assess the feasibility and acceptability of integrated PrEP/STI services and the impact of drug-level feedback on PrEP adherence among TGW in Uganda, we conducted a qualitative study to explore participant perspectives and experiences.

Methods

Population and Procedures

The Tandika PrEP Study was a randomized clinical trial conducted between November 2021 and July 2023 in Kampala, Uganda. Its objective was to assess the feasibility and acceptability of same-day initiation of TAF-based PrEP and the impact of drug-level feedback on PrEP adherence among TGW (ClinicalTrials.gov: NCT04491422). Study participants were recruited through peer-led sampling, including TGW previously enrolled in a TDF-based PrEP trial (NCT04328025) [27]. They were randomly assigned in a 1:1 ratio to receive either drug-level feedback with tailored adherence counseling using POC urine TFV levels (intervention) or standard adherence counseling without drug-level feedback (control). Tailored adherence counseling in the intervention arm involved quarterly Integrated Next Steps Counseling [iNSC], a strengths-based discussion identifying sexual health protection and PrEP adherence needs [28].

The randomization process was conducted using Research Electronic Data Capture (REDCap) software [29]. The trial utilized a community-based participatory research strategy [30] involving collaboration with TGW civil society groups, consulting TGW in grant and protocol preparation, selecting and training TGW peers as leaders in recruitment and retention efforts, and including TGW members on the research team and community advisory group. Potential power imbalances were addressed through open discussions to encourage the active participation of TGW throughout the trial. Due to the population’s vulnerability, perceived or experienced social harms were actively assessed using interviewer-administered questionnaires at clinic visits.

All TGW were enrolled at the study clinic, where they initiated PrEP on the same day and attended quarterly (3-month interval) appointments for 12 months. The SOC for TGW included: (a) dispensing three bottles of TAF/FTC medication, each with a one-month supply, (b) distribution of four HIV self-test kits (OraSure Technologies, USA) for personal use or testing with intimate partners, (c) free condoms and lubricants, (d) tailored counseling on minimizing the risk of HIV and other sexually transmitted infections (STI), and (e) monitoring of renal function every six months [31]. At each clinic visit, all participants received HIV testing with serial rapid tests: Determine^® HIV1/2 (Abbott, IL) [screening test], Stat-Pak HIV1/2 (Chembio Diagnostic Systems, Medford, NY) [confirmatory test], and SD-Bioline (Abbott, IL) [tie breaker test] according to national guidelines [13]. Using Xpert^® CT/NG (Cepheid Inc., USA), self-collected urine and rectal samples were tested for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT), with complimentary treatment provided as needed. At the time of the study, the standard of care was syndromic management of STIs; siloed PrEP and STI services were administered separately.

Adherence Counseling and Drug-Level Feedback

During quarterly visits, individuals in the intervention group were provided with iNSC [28]. This counseling approach utilized a strength-based and non-judgmental approach to identify the specific sexual health and PrEP adherence needs of transgender women (TGW) and develop tailored strategies to address these needs [28]. The counseling process involved assessing the participant’s understanding of PrEP, identifying any barriers to adherence, discussing potential side effects, addressing perceived obstacles related to taking PrEP as prescribed and evaluating self-reported adherence. Nurses underwent training and received mentorship from an experienced iNSC trainer who conducted on-site assessments to observe their implementation of iNSC. The trainer provided real-time feedback on their performance. As iNSC was initially developed in the United States, adjustments were made to adapt it to the context of Uganda through consultation with Ugandan researchers, counselors, and transgender community members. These adaptations considered cultural norms and expectations, which are typically more directive regarding shared problem-solving tailored to individual needs rather than explicit shared decision-making.

The main objectives of these counseling sessions were to (1) offer support to TGW who desired to adhere to PrEP, (2) emphasize the importance of sexual health as an integral aspect of self-care and overall well-being, and (3) conduct point-of-care urine tests for tenofovir (TFV) levels and provide feedback. The POC urine test produces a qualitative result indicating the presence of TFV at a concentration of ≥ 1500 ng/mL [23]. Our team has demonstrated that this cut-off can be applied to F/TDF and F/TAF dosing [32]. For TGW with urine TFV levels below 1,500 ng/mL, iNSC involved administering two 7-item questionnaires on PrEP adherence and sexual health to guide problem-solving for improved dosing [33]. Additionally, PrEP adherence was evaluated quarterly by measuring tenofovir diphosphate levels in dried blood spot samples, which were batch-tested after the trial [34]. The primary trial findings will be reported separately upon completion of endpoint testing.

Sampling and Recruitment

During follow-up visits for the parent trial, a random sample of 30 TGW in the intervention group was invited to participate in a qualitative study. Study staff contacted the TGW participants to schedule interviews.

Data Collection

Qualitative data collection commenced in April 2022 and concluded in February 2023. It entailed conducting individual, face-to-face interviews with the 30 TGW participants, which explored (1) perspectives on same-day initiation of TAF PrEP, (2) experiences of urine testing for TFV levels and receiving adherence counseling with drug-level feedback, and (3) descriptions of self-collection of samples for STI testing. Trained social scientists (AN, BK, JM, and VK), consisting of cisgender women and men, conducted all interviews in either English or Luganda (the local language). These conversations occurred at the participants’ chosen locations, ensuring they could not be overheard. The interview guides used during these sessions are in the supplementary appendix. Each interview lasted approximately 60 min and was audio-recorded with the participant’s consent. The interviewer then transcribed the recordings into English. To ensure accuracy, we conducted thorough quality checks for each transcript, comparing the transcript to the audio recording and making any necessary revisions to the transcript errors. As per IRB approval, each participant received a reimbursement of UGX 40,000 (US$10.70) for their participation.

Data Analysis

An inductive, content analytic approach was utilized to analyze the data [35]. The analysis commenced with thorough reviews of all interview transcripts focusing on experiences related to same-day PrEP initiation, drug-level feedback, and HIV/STI testing by AN, BK, JM, VK, and AM. Relevant content was identified and provisionally labeled through an iterative, open coding process. These labels were then defined, illustrated, and organized into a codebook. Subsequently, the codebook was used to organize the data using Dedoose software (SCRC, Hermosa Beach, CA). After completing the coding process, codes were employed to sort the data and propose concepts pertinent to same-day F/TAF initiation and urine tenofovir and STI testing. Based on these initial concepts, content categories describing experiences with TAF-based PrEP were developed. Each category comprises a descriptive label accompanied by an explanatory text and interview quotes illustrating the concept. These categories are intended to comprehensively represent all primary concepts present in the data. We reached saturation during this process. Our study findings were reported following the COREQ checklist [36].

Ethics Approval

The Mildmay Uganda Research Ethics Committee (0105–2020), Uganda National Council for Science and Technology (HS772ES), and Partners Human Research Committee (Massachusetts General Hospital; 2020P002359) all approved the study. Before participation, each qualitative study participant provided written informed consent in English or Luganda.

Results

Participant Characteristics

At enrollment, the median age was 20 years for the 30 TGW participants (interquartile range [IQR] 19–22), and the median duration of schooling was 11 years (IQR 10–12) (Table 1). They reported a median monthly income of UGX 200,000 ($52.98); at the time of the study, Uganda’s average monthly income was UGX 416,000 ($107.74) in 2018 [37]. TGW reported a median of 10 anal sex acts (IQR 5–15) in the prior month. Most (27; 90%) had any access to lubricants, 25 (83%) reported having access to condoms, and 20 (70%) engaged in sex work. Twenty-eight TGW (93%) had ever taken alcohol.

Table 1.

Baseline characteristics of TGW participants (N = 30)

Characteristic	Median (IQR) or N (%)
Age (years)
<25	28 (93)
≥25	2 (7)
Education (years)
≤10	6 (20)
>10	24 (80)
Monthly income (UGX+)	200,000 (100,000, 300,000)
Partnership status
Intimate partner	20 (67)
No intimate partner	10 (33)
Access to condoms	24 (80)
Access to lubricants	30(100)
Sells sex for money or goods	24 (80)
Currently taking alcohol	19 (63%)
Currently taking tobacco	6 (20%)
Currently using recreational drugs	4 (13%)
Ever incarcerated	10 (33%)
Ever incarcerated for being transgender (n = 10)	9 (90%)

^*IQR – interquartile range

⁺UGX – Uganda Shillings; quantitative data derived from parent clinical trial

Qualitative Results

We present three categories to illustrate the experiences of integrated PrEP/STI care for TGW participants. Firstly, TAF’s desirable attributes, such as a compact pill size, good tolerability, and novelty, facilitated ease of use and mitigated the HIV-related stigma associated with taking antiretroviral drugs. TAF-associated weight gain was positively perceived because of African preferences for larger body size and its association with health and prosperity. Secondly, PrEP adherence was motivated by not wanting to disappoint healthcare workers. TGW reciprocated the adherence support they received by taking PrEP to avoid tenofovir non-detection in urine. Thirdly, urine testing facilitated STI care and adherence, acting as a helpful reminder and motivating factor for TGW to adhere to PrEP. Utilization of urine for tenofovir and STI testing motivated the uptake of integrated PrEP/STI care. Overall, TGW expressed appreciation for the convenience of integrated PrEP/STI services, including the novelty of TAF-formulated PrEP, which was more convenient and tolerable than F/TDF and helped them avoid potential stigma related to using PrEP.

Category 1: F/TAF-based PrEP was Easy to Take Because of Its Compact Size and Novelty

Desired F/TAF attributes included its smaller pill size and drug novelty.

TGW clearly expressed a preference for F/TAF, which they referred to as the “new PrEP” due to its smaller pill size, making it easier to swallow than the larger F/TDF pills to which they had become accustomed. The large pill size of the “old PrEP” was described as “discouraging,” with one participant stating that “you pray first before taking it.” In contrast, the convenience of taking the small F/TAF pill “without water” was considered advantageous in a setting where tap water is unsafe to drink. Notably, F/TAF was unavailable through the public health system at the time of the study, making it novel and appealing to TGW. They could take it discreetly in the presence of friends and family without them knowing that it was an antiretroviral drug. This was highlighted by one young woman who stated, “You don’t feel ashamed even when you take it in public.” Unlike F/TDF, which was bulkier and perceived as less portable, F/TAF could be conveniently carried due to its compact size.

“I spend most of my time with straight people whom I did not want to know that I am taking PrEP. With the big-sized [F/TDF] pills, I would not be comfortable taking them in their presence, and besides, it was hard moving with them. However, with the small-sized [F/TAF] pills, I knew I would move with them anywhere I wanted.” (TGW, age 24).

“This new PrEP helps me a lot. It is a small tablet which will not get stuck in my throat. But the other old PrEP, I would take it and feel like I want to vomit. But with this new drug, it is easy to swallow.” (TGW, age 20).

F/TAF-based PrEP was well tolerated.

Initial experiences with F/TAF were often accompanied by side effects such as dizziness, nausea, and vomiting. However, these were manageable and typically resolved over time. Generally, TGW perceived F/TAF as more tolerable than F/TDF, stating that “It doesn’t [have] severe side effects.” They attributed any side effects experienced to “PrEP trying to adapt to my body.” Some perceived increased appetite and weight gain as positive outcomes. As one TGW stated: “I just got more motivated to take PrEP.”

“When I was taking the big PrEP pills, I was always weak and would always feel dizzy and felt like sleeping all the time. With the new small PrEP pills, I still had a high appetite, although the dizziness and nausea disappeared. My appetite was very high, and I did not mind so much about it. You only worry about your appetite when you don’t have what to eat, but when God helps you, and you have what to eat, you eat.” (TGW, age 23).

“The first time, I was kind of uncomfortable. I used to vomit [but] I slowly got used to it. I started gaining weight; my appetite was high. The first time I came here (study clinic), I weighed 51 kg, and when I came back for the second visit after three months, I was 66.3 kg. Right now, as we speak, I am 61 kg. I feel good because being small is not good.” (TGW, age 19).

Category 2: PrEP Adherence was Motivated by Not Wanting to Disappoint Healthcare Workers

Urine tenofovir testing served as a reminder and motivation to take PrEP.

Study participants initially expressed apprehension about the purpose of urine tenofovir testing, which, to them, indicated a lack of trust in their self-reported adherence. One TGW questioned, “Do you think I am a scammer?” Despite these concerns, participants were grateful for the free urine tenofovir testing provided by the study. The prospect of receiving feedback on tenofovir drug levels at their next clinic visit served as a reminder for TGW participants to maintain adherence to PrEP. This was driven by a desire for tenofovir to be detected in their bodies as proof of following prescribed PrEP regimens. The knowledge that PrEP was present in their system served as motivation for continued adherence to PrEP and subsequently obtaining a positive test at their next clinic visit.

“At first, I thought they don’t trust us if we do take PrEP. But it is so helpful to see if PrEP is really existing in your body. The [nurse] told me that we have tested your urine to see if you are taking PrEP, but you do take it very well. It has been detected in the urine, so continue taking your PrEP very well. I was like since they have detected PrEP in my urine, let me continue taking it well such that next time I come back, PrEP is there.” (TGW, age 19).

“By the way, it is one of the things which reminds me to take my PrEP. Whenever I think about testing my urine to see if I take PrEP, if I forget and it approaches 7 pm, I feel like there is something I have not done because I am now used to it. It is a daily routine. So, I get my PrEP and take it because I would know that the health worker will test for it in my urine. After all, the testing is free.” (TGW, age 19).

TGW reciprocated the study staff’s commitment to their health by adhering to PrEP.

Encouragement from staff motivated consistent pill-taking. TGW appreciated being thanked by the study staff for taking PrEP. This validation made them feel cared for and encouraged them to remain committed to taking their medication even during moments when they did not feel like taking their pills. Study participants demonstrated dedication to their health and well-being by adhering to the prescribed PrEP regimen. They recognized their healthcare providers’ investment in their health and did not want to disappoint them.

“Yeah, going to the hospital where you are getting services from, and then someone says thank you for taking PrEP. That is really a good thing. It really motivates me a lot. It is like, okay, even this person wants my life to be on the safe side. Someone to be happy because you are taking your drugs very well; it is also a good motivation.” (TGW, age 22).

“…sometimes you can be in the mood of not feeling like taking your drugs. But you reach a point and take it for the good of your life and the betterment of the facility that gave you this medicine to take. And if I go back to the facility but when I don’t take the drugs, they will be disappointed [knowing] we are just wasting the resources. So, this encourages me to take it daily because I want them to detect it in my urine whenever they test it.” (TGW, age 21).

Awareness of adherence for prevention motivated honesty regarding pill-taking.

TGW who faced challenges adhering to their prescribed PrEP medication acknowledged that any misrepresentation of self-reported pill-taking would not align with the results of urine tests. They were aware that failure to take PrEP as prescribed and engaging in sexual activity without a condom could potentially lead to HIV acquisition. They stated that open and honest communication with healthcare providers was crucial, as falsifying information about PrEP usage could be detected through urine testing and a positive HIV test. Moreover, they recognized that non-detection of tenofovir in urine could absolve study staff from potential blame if seroconversion were to occur. This realization prompted them to take personal responsibility for both their adherence and their sexual behaviors. Furthermore, receiving positive feedback for detecting tenofovir in their urine further reinforced these behaviors.

“I am not taking my pills, and yet I tell the health worker that I am taking my pills. In case I have sex with someone who is HIV-positive, and I end up contracting the virus, I will not tell the health worker that I was not adhering well to my drugs. If my sample is taken and the health workers get to know that I am not taking PrEP, they will find a way of helping me. If I do not take my PrEP pills as prescribed and I end up contracting HIV, I might blame the health workers because it is them who assured me that when I take PrEP, I will not contract HIV, and yet deep inside my heart, I know I have been having unsafe sex and above all not taking PrEP. I had to adhere well to PrEP because of the assured protection that I get, and when my sample is tested, and there is proof that I am indeed taking PrEP, it helps a lot.” (TGW, age 23).

“Well, she told me I didn’t have PrEP in my system. Just because my [pill taking] was not consistent. I used to skip a couple of days. But of course, I knew [the] personal advantage of taking PrEP. So, even though they didn’t find it in my system, I was not dismayed or in any way heartbroken. Next time, I know it will be different.” (053, age 22).

Category 3: Urine Testing Facilitated STI Care and PrEP Adherence

Newfound knowledge of STI status improved treatment literacy.

TGW recognized the practicality of utilizing urine as a means of testing for both tenofovir and STIs. As reported by one participant, “…there are other things he is going to test in my urine, like candida, so I give it out willingly.” However, some TGW lacked knowledge about STIs and consequently did not seek testing to know their status. Others actively chose to “ignore such diseases” and avoided clinic visits to be tested and “get to know the truth.” Learning the results of STI tests led to a better understanding of these infections, including how they may be present in the body, even in the absence of symptoms. TGW also became aware of their potential to transmit STIs to their sexual partners. This newfound awareness emphasized to them the importance of adhering to the prescribed course of antibiotics for proper treatment and prevention of further infection.

“I had gonorrhea and chlamydia. All these were new to my ears. When I was told what I was suffering from, I was like, ‘Jesus Christ, what is happening to me?’ I was given some tablets, which I took religiously, and when I came back, I was [cured]. I had syphilis, which had been in my body for a long time. I was given six injections for six weeks, one injection every week on Monday. When I went back to test for both HIV and STIs, the results came back negative for both.” (TBW, age 19).

“I feel so happy because we normally ignore such diseases, yet they are very dangerous. There are some diseases that we take too long to know that they are affecting us, and by the time you get to know that you are suffering from this or that, you could have infected many. One thing that we fear most is to be told the truth. A health worker can tell you that we have found this and that and give medication. You get the drugs, but then do not take them, forgetting that it is your life and not for the health worker.” (TBW, age 23).

Fear of disclosure and lack of testing for sexual partners limited the benefits of STI testing.

The social stigma surrounding STIs hindered individuals from seeking necessary testing and treatment services. This was particularly true for TGW in this study, who often faced added fears of unintentionally revealing their sexual orientation while accessing testing services in this study. Furthermore, some TGW were concerned the study did not extend testing services to their sexual partners. Not knowing that their partners were also STI-free contributed to feelings of anxiety.

“I was afraid to openly tell the health workers to test me for STIs. How dare I tell the health worker that I have got anal warts? She would be suspicious and wonder about a man suffering from anal warts.” (TGW, age 21).

“They test us for STIs, but our partners are not tested. That is one of the challenges we are facing. I would suggest that, if possible, let our partners also be tested for STIs. You feel comfortable when both of you are free from STIs.” (TGW, age 24).

STIs were regarded with greater apprehension than HIV.

STIs were a more feared consequence of sexual activity than HIV. This belief stemmed from the misconception that STI symptoms were readily apparent, unlike HIV, which was perceived to have a delayed onset of illness. However, it was not fully understood that individuals could be infected with an STI without experiencing any symptoms, leading to surprise upon receiving a positive test result.

“I fear STIs more than HIV. I felt good in that when they asked for my samples, I just gave them out in good faith so that I get to know my STI status. When they tested, I was negative”. (TGW, age 29)

“I didn’t come here with the intention of testing for STIs. I thought that they were going to test for tenofovir. But the health worker told me that when she tested my urine, she found out I [had] gonorrhea. I was like, ‘Where could I have got it from?’ Truth be told, I could not tell who infected me with an STI because I had slept with different people. But when she gave me the medication, I took it properly and healed.” (TGW, age 22).

Discussion

This qualitative research, conducted among transgender women participating in a randomized trial of integrated PrEP and STI services in Kampala, Uganda, revealed that the desirable attributes of F/TAF, such as a compact pill size, tolerability, and novelty, influenced the uptake and use of TAF-based PrEP. The introduction of this new drug helped mitigate the societal stigmatization surrounding HIV by providing an alternative to TDF-based PrEP that was not associated with HIV. Additionally, participants viewed the weight gain associated with F/TAF use positively, as it symbolized wealth and good health in the culture. Urine testing for tenofovir levels motivated individuals to use PrEP and accurately report their adherence. Counseling and drug-level feedback helped foster reciprocity among TGW, who desired to mirror the perceived dedication of study staff to maintaining their health. Urine testing also facilitated STI detection and treatment. While HIV was a significant concern, STIs were even more feared consequences of sexual activity. The social stigma surrounding STIs sometimes hindered individuals from seeking necessary testing and treatment services. Nevertheless, TGW valued and appreciated the opportunity for testing as it enhanced their understanding of treatment options and ultimately improved their overall health.

To our knowledge, this is the first qualitative evaluation of TAF-formulated PrEP for TGW in Africa. The preference for F/TAF over F/TDF was primarily based on product characteristics, such as its smaller pill size and fewer side effects. Its relative “newness” in the market made it a more appealing option than F/TDF because it was not known to be an antiretroviral drug. Previous research involving 223 PrEP users in the US (including 219 cisgender men and 2 TGW) reported that reasons for switching from F/TDF to F/TAF included smaller pill size, perceived enhanced safety, and the novelty of F/TAF [38]. Other qualitative research with gay and other MSM in the USA has shown that concerns about poorer adherence and the side effects associated with F/TDF influenced drug switching to F/TAF [39]. Our findings are consistent with these results. Data on the usage of F/TAF PrEP in sub-Saharan Africa is currently limited, primarily due to the limited availability of the drug in this region. However, the recently concluded PURPOSE 1 trial (NCT04994509) will contribute efficacy data on F/TAF use by cisgender African women [40]. Implementing PrEP access programs will help ensure that even marginalized populations can obtain F/TAF.

Weight gain associated with F/TAF was desirable in a cultural context where higher body weight was positively perceived [41]. In several African nations, being overweight is often equated with wealth, wellness, vigor, and fertility [42], indicating abundant resources in settings where food scarcity is prevalent [43]. Several HIV treatment studies have shown that F/TAF is independently associated with weight gain [44–46]. It has been observed that antiretroviral-induced weight gain is more prevalent among individuals with African ancestry [47]. However, significant differences were noted between countries, with Nigeria showing a higher rate of weight gain while Uganda reported minimal changes [48]. In the DISCOVER study, TGW using TAF-based PrEP gained an average of one kilogram (2.2 pounds) after 48 weeks [11]. In contrast, data from seven other PrEP trials indicates that F/TDF may be associated with weight loss [49]. Qualitative research with cisgender women receiving dolutegravir-based HIV treatment in Uganda found that they aspired to gain weight to enhance their body image, social standing, and psychosocial well-being [50]. Healthcare workers should discuss these perceived benefits of TAF-based PrEP with TGW in a sensitive and non-judgmental manner. This includes acknowledging that traditional recommendations for weight loss through dietary and lifestyle changes may not be practical if these individuals desire a larger body size. However, it is essential to recognize the adverse metabolic effects of TAF, which include elevated serum lipids and an increased risk of atherosclerotic cardiovascular disease, hypertension, diabetes mellitus, and nonalcoholic steatohepatitis when compared to TDF [51–53].

Our results suggest that urine tenofovir testing potentially improved the accuracy of self-reported adherence. This is because discrepancies between actual pill-taking behavior and detection of tenofovir in urine were deemed socially unfavorable. Reasons for misreporting adherence include guilt over not conforming to prescribed pill-taking behaviors, fear of adverse treatment by study staff, and the perceived negative consequences of reporting nonadherence, such as being discontinued from research studies or programs [54, 55]. The validation of drug intake through urine testing spurred a sense of accountability for pill-taking and safer sexual practices. Additionally, it motivated TGW to reciprocate the commitment of study staff to improving their health. Prior qualitative research involving 27 cisgender people and one transgender woman found initial resistance towards drug-level monitoring but an eventual acceptance of urine tenofovir testing [56]. Cisgender women in Kenya reported that POC urine testing encouraged PrEP adherence because they wanted to receive positive results [55, 57]. Additionally, drug detection decreased anxiety about HIV acquisition. Future efforts to optimize adherence counseling with drug-level feedback should destigmatize negative results, clarify that POC testing is not intended to identify dishonesty in self-reported adherence, and acknowledge the short period of drug exposure.

In our study, TGW valued free STI testing and treatment. Concerns about STIs outweighed those about HIV, yet barriers such as social stigma and apprehension about revealing their sexual orientation hindered their ability to access these services. Using urine for both STI and tenofovir testing was convenient, resulting in increased uptake of free STI testing. This highlights the potential benefits of integrating POC testing services in PrEP programs to reduce the incidence of both HIV and STIs, given their synergistic relationship [58]. A study of urine tenofovir testing among TGW in the USA revealed modest detection rates (> 70%) for tenofovir levels. Yet, no significant difference was observed in sexual partner numbers or STI diagnoses during the 48-week study period [59]. A systematic review of 91 studies from 32 countries found that most (70%) conducted STI testing before PrEP initiation [58]. Consistent with our research, the most frequently tested STIs were gonorrhea (86%), chlamydia (84%), and syphilis (84%). However, the integration of STI testing into PrEP programs in low-resource settings was hindered by financial constraints, limited access to STI diagnostics, and limited capacity building for staff involved in PrEP provision. Future research should focus on optimizing the integration of STI services into PrEP programs and the need for POC STI testing within differentiated delivery models [60].

Our study has several strengths, including being the first qualitative evaluation of TAF-based PrEP, drug-level monitoring, and integrated PrEP/STI services for TGW in sub-Saharan Africa. Using qualitative data allowed a comprehensive understanding of how TAF-based PrEP and urine testing for tenofovir and STIs were experienced. Additionally, one of our authors identifies as transgender, providing valuable insight during our interpretation of the data. We also involved transgender colleagues in study implementation, including reviewing data collection instruments, recruiting and retaining participants, reviewing the manuscript, and disseminating the results. The limitations of this study include the clinical trial setting, which may not accurately represent the implementation of PrEP in a real-world environment where F/TAF is not accessible through public health systems. As with all qualitative research studies, our findings cannot be generalized and should not be interpreted as such. Nevertheless, they can provide valuable insights for integrating TAF-based PrEP and STI services in other African settings.

Conclusions

Integrating PrEP and STI services into current delivery models and offering a choice of PrEP options to TGW, including long-acting formulations that overcome some of the limitations of a daily pill, can enhance prevention efforts in this underserved population. Point-of-care testing for PrEP adherence using a urine tenofovir assay is acceptable, motivates adherence, and can be combined readily with POC testing for STIs. Collaborative initiatives to expand access to generic F/TAF and PrEP adherence/STI testing could improve affordability and utilization among this demographic.