
==== Front
J Acquir Immune Defic Syndr
J Acquir Immune Defic Syndr
qai
Journal of Acquired Immune Deficiency Syndromes (1999)
1525-4135
1944-7884
JAIDS Journal of Acquired Immune Deficiency Syndromes

39250646
QAIV23486
10.1097/QAI.0000000000003471
00004
3
Prevention Research
Peer-Delivered HIV Self-Testing, Sexually Transmitted Infection Self-Sampling, and Pre-exposure Prophylaxis for Transgender Women in Uganda: A Randomized Trial
https://orcid.org/0000-0001-6646-6733
Mujugira Andrew MBChB, PhD ab
Karungi Beyonce cbeyonce30a@gmail.com

Nakyanzi Agnes BScM aanakyanzi@idi.co.ug

Bagaya Monica BPH amonicabagaya@gmail.com

Nsubuga Rogers BStat arnsubuga@idi.co.ug

Sebuliba Timothy BPH atssebuliba@idi.co.ug

Nampewo Olivia RN aonampewo@idi.co.ug

Naddunga Faith RN afnaddunga@idi.co.ug

Birungi Juliet E. RN aebirungi@idi.co.ug

Sapiri Oliver RN aOSapiri@idi.co.ug

Nyanzi Kikulwe R. Dip MLT akrnyanzi@yahoo.co.uk

Bambia Felix BSc afbambia@idi.co.ug

Muwonge Timothy MBChB, MPH atmuwonge@idi.co.ug

Gandhi Monica MD, MPH dMonica.Gandhi@ucsf.edu

Haberer Jessica E. MD, MS efJHABERER@partners.org

a Research Department, The Infectious Diseases Institute Limited, Makerere University, Kampala, Uganda;
b Department of Global Health, University of Washington, Seattle, WA;
c Transgender Equality Uganda, Kampala, Uganda;
d Department of Medicine, University of California San Francisco, San Francisco, CA;
e Harvard Medical School, Boston, MA; and
f Center for Global Health, Massachusetts General Hospital, Boston, MA.
Correspondence to: Andrew Mujugira, MBChB, PhD, The Infectious Diseases Institute Limited, P. O Box 22418, Kampala, Uganda (e-mail: amujugira@idi.co.ug).
1 10 2024
17 6 2024
97 2 125132
16 11 2023
22 4 2024
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Supplemental Digital Content is Available in the Text.

Background:

Peer-delivered HIV self-testing (HIVST) and sexually transmitted infection self-sampling (STISS) may promote adherence to oral pre-exposure prophylaxis (PrEP), but no studies have analyzed this approach among transgender women (TGW) in sub-Saharan Africa.

Setting:

The Peer study was a cluster randomized trial in Uganda (October 2020–July 2022; NCT04328025).

Methods:

Ten TGW peer groups, each with 1 TGW peer and 8 TGW, were randomized 1:1 to receive quarterly in-clinic HIV testing with PrEP refills as standard-of-care (SOC) or SOC plus monthly peer delivery of oral-fluid HIVST, STISS, and PrEP refills (intervention). Participants were followed for 12 months. The primary outcome was PrEP adherence.

Results:

We screened 85 TGW and enrolled 82 (41 per arm). The median age was 22 years (interquartile range [IQR] 20–24). Twelve-month retention was 88% (72/82). At the 3, 6, 9, and 12-month clinic visits, 10%, 5%, 5%, and 0% of TGW in the intervention arm had TFV-DP levels ≥700 fmol/punch, versus 7%, 15%, 7%, and 2% in the SOC arm, respectively (P = 0.18). At all visits, any detectable TFV-DP levels were significantly higher in SOC than the peer delivery group (P < 0.04). PrEP adherence was associated with sex work (incidence rate ratio 6.93; 95% CI: 2.33 to 20.60) and >10 years of schooling (incidence rate ratio 2.35; 95% CI: 1.14 to 4.84). There was a strong correlation between tenofovir detection in dried blood spots and urine (P < 0.001). No HIV seroconversions occurred.

Conclusions:

Peer-delivered HIVST and STISS did not increase low levels of oral PrEP adherence among TGW in Uganda. Long-acting PrEP formulations should be considered for this population.

Key Words:

peer
HIV self-testing
STI self-sampling
PrEP
adherence
transgender women
National Institute of Mental HealthR34MH121084 Andrew MujugiraOPEN-ACCESSTRUE
SDCT
==== Body
pmcINTRODUCTION

The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a global 2025 goal of 95% of those at risk of HIV infection using effective, person-centered HIV prevention combination options.1 Transgender women (TGW; those who were assigned male sex at birth but identify as female) have a 14-fold greater risk of acquiring HIV than adults in the general population.2 Globally, the prevalence of HIV is 20% among TGW, with a pooled odds ratio of 66 for HIV infection compared with all persons aged 15 years or older.3 Studies in sub-Saharan Africa suggest that TGW have higher HIV prevalence and incidence than men who engage in sexual activity with other men (MSM).4–7 For example, HIV incidence is 5 times greater among TGW in Kenya (20.6 per 100 person-years) compared with cisgender MSM (4.5 per 100 person-years).4 TGW also have higher levels of rectal sexually transmitted infections (STI) than cisgender men in Kenya (P < 0.02).5 In the preceding study, the prevalence of rectal Neisseria gonorrhea (NG) and Chlamydia trachomatis (CT) was 21% and 7%, respectively.

Several tools and delivery strategies are available to facilitate HIV/STI prevention among TGW. HIV self-testing (HIVST) and self-collection of STI samples are self-care interventions recommended by the World Health Organization (WHO) to facilitate the delivery of HIV and other STI testing services.8 STI self-sampling (sexually transmitted infection self-sampling (STISS)) for etiologic diagnosis of CT and NG is feasible, acceptable, and comparable with specimens collected by providers in resource-limited settings,9,10 according to studies conducted among TGW.11 Pre-exposure prophylaxis (PrEP) is an evidence-based prevention intervention that is highly effective in reducing the risk of sexual HIV transmission.8 The WHO recommends incorporating peer support into HIV testing and PrEP delivery processes, particularly for hidden populations.12,13

Differentiated service delivery approaches, such as task shifting to TGW peers and combining HIV/STI testing and PrEP, could improve access to and availability of combination prevention options.8 Peer-delivered services are a client-centered approach that could maximize the coverage and effectiveness of HIV/STI and PrEP services for TGW.14,15 Moreover, peer-delivered HIVST and STISS have the potential to expand the reach, frequency, and efficacy of HIV/STI testing among TGW and their sexual partners,16,17 allowing TGW who may not usually test—or test infrequently—to take control over their own testing decisions in a way that provides autonomy and freedom.18–20 However, it is unknown to date to what extent peer delivery increases HIV/STI testing rates and status knowledge, creates demand for repeat testing, and encourages PrEP use among TGW in sub-Saharan Africa. Furthermore, little is known about the use and impact of peer-delivered services among TGW in sub-Saharan Africa; TGW may reciprocate peer support and perceived investment in their health by adhering to PrEP. We conducted a randomized trial to evaluate whether providing peer-delivered combination prevention (HIVST, STISS, and PrEP) would increase testing uptake and adherence among HIV-negative TGW initiating PrEP in Uganda.

METHODS

Trial Design

The Peer study was a cluster randomized trial conducted in Kampala, Uganda, from October 2020 to July 2022 (NCT04328025). Ten peer groups (each with 1 TGW peer and 10 TGW participants) were randomized in a 1:1 ratio to either quarterly in-clinic testing and receipt of PrEP medications as standard-of-care (SOC) or SOC and monthly peer-delivered HIVST, STISS, and PrEP (intervention) using block randomization.21 Study participants, peers, and providers were not blinded to assignment based on the nature of the intervention. Participants were permitted to switch peers within randomization groups. The trial protocol did not significantly change after enrolment. The primary objective was to pilot-test the preliminary effectiveness of peer-delivered HIVST and STISS on PrEP adherence among TGW in the study. We hypothesized that peer support for HIVST and STISS would be perceived by TGW as an investment in their health, motivating them to reciprocate by taking PrEP.22 A qualitative exploration of how peer-delivered HIVST, STISS, and PrEP influenced prevention uptake among TGW and their intimate partners is reported elsewhere.22 All study procedures were conducted with approval from the Ugandan authorities. The trial ended before the enactment of the Anti-Homosexuality Act in May 2023.

The peer delivery intervention was guided by the socioecological framework for PrEP introduction.23 Before implementation, formative research was conducted, which involved conducting 20 in-depth interviews with TGW peers. Interviews explored the following: (1) barriers and facilitators of peer-delivered combination HIV prevention and (2) preferences for HIV/STI testing approaches and PrEP refills. The insights gained from formative research informed intervention design.24 TGW peers identified during the formative research were trained by study staff for 2 weeks to administer the peer delivery intervention and to protect research participants' privacy.22 On completion of training, they were officially employed by the research institution and provided with formal authorization letters to distribute test kits and oral PrEP. This trial is reported following the Consolidated Standards of Reporting Trials statement.25

Population and Procedures

TGW participants were enrolled using peer-led snowball sampling in Kampala, Uganda, between October 26, 2020, and April 27, 2021, and followed for 12 months. The trial ended on July 31, 2022. Participant sex was self-identified. At study entry, eligible participants were at least 18 years of age, or if 14–17 years, had qualified as a mature or emancipated minor due to having an STI or receiving money or goods in exchange for sexual services.26 Eligible participants also reported condomless anal sex in the prior 6 months, tested negative for HIV and HBV, were willing to take PrEP, complied with study procedures, and had adequate renal function (creatinine clearance ≥60 mL/minute). The exclusion criteria for this study were participation in any other biomedical HIV prevention study, any illness that would prevent the provision of informed consent, and intent to move away from the study's catchment area.

Each month, trained TGW peers delivered 2 HIV self-tests (OraQuick rapid HIV-1/2 self-test kits; OraSure Technologies) and PrEP refills, distributed STI self-sampling kits, and taught TGW in the intervention arm how to self-collect oropharyngeal, rectal, and urine specimens. At each quarterly clinic-based visit, TGW in both arms received 4 HIVST kits as follows: 2 for own use and 2 for testing sexual partners. All study participants received quarterly in-clinic HIV rapid testing as SOC. All participants were offered coformulated lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg (FTC/TDF) as PrEP; those in the intervention arm received monthly refills from their peers, while those in the SOC arm obtained a three-month supply at each quarterly clinic visit. PrEP adherence was measured using tenofovir–diphosphate (TFV-DP) levels in dried blood spot samples (dried blood spots (DBS)) collected at quarterly clinic visits.27 Data on PrEP adherence and sexual risk behaviors were obtained during monthly phone interviews and quarterly in-person visits.28 TGW were also screened for depression with the Patient Health Questionnaire,29 and a study nurse escorted those with PHQ-9 scores ≥10 to the psychiatry clinic. Study interactions occurred in either English or Luganda (local language), and participants were provided additional HIV prevention services, including individualized HIV and PrEP counseling, condoms/lubricant distribution, and free syndromic STI screening/treatment per national guidelines.30 Beginning in January 2021, 3 months after the study commenced, urine tenofovir point-of-care testing31 with subsequent drug-level feedback was used to support adherence counseling in real-time. Studies have shown that identifying PrEP nonadherence through urine testing, followed by adherence counseling, has improved adherence.32–34 During clinic visits, research nurses requested that TGW provide a urine sample that was tested in their presence. Study participants in both arms received real-time drug-level feedback and adherence counseling during their quarterly clinic visits; qualitative findings are reported elsewhere.22 All participants were clinically monitored for adverse events. Each received an IRB-approved reimbursement of UGX 30,000 (US$8.10).

Laboratory Methods

TGW were tested for HIV using serial rapid tests according to national guidelines.35 In addition, HBV testing was performed using Pal HBsAg rapid tests (Healgan Scientific). Quarterly, samples from all TGW were taken from the oropharyngeal, rectal, and urethral sites and tested for NG and CT using the Cepheid GeneXpert CT/NG assay.36 In addition, those in the intervention arm had monthly testing. Serum creatinine testing was conducted using a Cobas Integra 400 biochemistry analyzer (Roche, Germany). Intracellular TFV-DP levels in DBS were quantified using validated liquid chromatography/tandem mass spectrometry methods at the University of Cape Town Clinical PK Laboratory, South Africa.37 This allowed for a comprehensive evaluation of short-term (urine) and long-term (DBS) adherence metrics.38

Statistical Analysis

Primary outcome measures were (1) acceptability of peer-delivered HIVST, STISS, and PrEP evaluated through HIVST uptake and use and STI testing rates; (2) feasibility of peer-delivered combination HIV prevention as assessed by the proportion of expected HIVST and STISS kits delivered and used; and (3) intervention effectiveness (adequate PrEP adherence measured using TFV-DP ≥700 fmol per punch and urine tenofovir ≥1500 ng/mL). PrEP was the standard of care at the time of the study, and all TGW were offered PrEP at enrolment. Thus, we did not measure PrEP acceptability. Secondary outcomes were (1) condomless sex and (2) CT/NG incidence. The primary analysis was an intent-to-treat comparison of PrEP adherence by randomization arm. Participants were included in the analysis if they received an HIV test at enrolment. The trial had 86% power to detect a 50% increase in HIV testing rates in the intervention arm with a sample size of 80 TGW assuming a mean testing rate in the control arm of 80%, intracluster correlation of 0.20, 5 peer groups per study arm, 8 TGW per peer group, a 10% loss to follow-up, and a 2-sided alpha of 0.05. Associations between PrEP adherence, sociobehavioral factors, and condomless sex were compared between the intervention and control arms using a GEE model with identity link, exchangeable correlation structure, and robust variance estimations. Covariates included in the model were age, education, duration of partnership, intimate partner violence, and alcohol use based on known associations with PrEP adherence.39 As categorized above, Spearman correlation was used to evaluate the relationship between TFV-DP levels in DBS and urine TFV levels. Statistical analyses were performed using Stata 14 (StataCorp).

Ethics Approval

The study was approved by the Mildmay Uganda Research Ethics Committee (0304–2019), Partners Human Research Committee (Massachusetts General Hospital; 2019P001620), and Uganda National Council for Science and Technology (HS390ES). Each participant provided written informed consent.

RESULTS

Population Characteristics

We screened 85 TGW and enrolled 82 (41 per arm). The median age was 22 years (interquartile range [IQR] 20–24) (Table 1). Nearly all (97%) had never used hormone therapy, 54% had intimate partners, 40% reported sex work, and 37% had ever been incarcerated. The median age at onset of sex work was 18 years (IQR 17–20), and the median monthly income was UGX 250,000 ($67.49). Among those engaged in sex work, the median charge for receptive anal sex was UGX 100,000 ($26.79) without a condom and UGX 60,000 ($16.07) with a condom, respectively. Overall participant retention (completed study visits) was 89% (73/82), 83% (68/82), 70% (57/82), and 88% (72/82) at 3, 6, 9, and 12 months, respectively. Twelve-month visit completion was 90% (37/41) and 83% (35/41) in the peer delivery and SOC arms, respectively, with no differences by arm (P = 0.99). There was one participant death unrelated to research participation.

TABLE 1. Enrolment Characteristics by Randomization Arm

Characteristic	Peer Delivery (N = 41)
N (%) or Median (IQR)	Standard of Care (N = 41)
N (%) or Median (IQR)	
Age (median, IQR)	22.0 (20.0, 24.0)	21.0 (20.0, 23.0)	
Currently using PrEP	
 Yes	5 (12)	7 (17)	
 No	36 (88)	34 (83)	
Partnership status	
 Intimate partner	25 (61)	19 (46)	
 No intimate partner	16 (39)	22 (54)	
Sexual partners in prior month	3 (2–3)	3 (2–3)	
Completed years of education	11 (9–13)	11 (10–13)	
 ≤10	15 (37)	12 (29)	
 >10	26 (63)	29 (71)	
Monthly income (UGX)	250,000 (150,000–330,000)	200,000 (200,000–300,000)	
Sex work	
 Yes	29 (71)	33 (80)	
 No	12 (29)	8 (20)	
Age at onset of sex work (years)	19 (17–20)	18 (17–19)	
Average charge for anal sex with a condom	50,000 (50,000–100,000)	100,000 (40,000–150,000)	
Average charge for anal sex without a condom	50,000 (32,500–90,000)	130,000 (20,000–150,000)	
Ever incarcerated (n = 62)	
 Yes	9 (31)	14 (42)	
 No	20 (69)	19 (58)	
If yes, incarcerated for being transgender	
 Yes	5 (14)	21 (41)	
 No	32 (86)	30 (59)	
Ever used hormone replacement therapy (n = 39)		
 Yes	1 (5)	0 (0)	
 No	19 (95)	19 (100)	
Possible depression*	
 Yes	26 (63)	26 (63)	
 No	15 (37)	15 (37)	
Alcohol use†	
 Yes	26 (63)	30 (73)	
 No	15 (37)	11 (27)	
* The Patient Health Questionnaire, which has been validated in Uganda29, was used to assess depression; a response of “yes” to either question is considered possible depression.

† Alcohol use was assessed using the RAPS-4 scale40.

Intervention Acceptability and Feasibility

In the peer delivery arm at enrolment, 98% (80/82) were willing to perform self-testing, and 89% (73/82) were aware of HIVST, with 60% preferring oral-fluid self-tests over blood-based tests. At 3, 6, 9, and 12 months, respectively, 90%, 100%, 93%, and 91% of participants accepted HIV self-tests from their peers; of those receiving the peer-delivered HIVST, 97%, 100%, 93%, and 91% reported using the test kits. At enrolment, 24% of participants in the intervention arm were aware of STISS. Nearly all were willing to collect STI samples, and 97% said they would consider asking their sexual partners to use self-collection kits. The proportion of those in the intervention arm who received self-collection kits from peers was 85%, 100%, 93%, and 87%, respectively, at the 3, 6, 9, and 12-month visits. Of those who received kits, all found the STI self-collection kit easy or very easy to use, with 100% expressing confidence in demonstrating how to self-collect samples for STI testing and recommending it to their friends and relatives. At study exit, 97% (30/31) of those who received self-collection kits reported that self-sampling was easy or very easy. All TGW who attended each quarterly visit used STI self-collection kits: 33/33 at month 3, 35/35 at month 6, 28/28 at month 9, and 31/31 at month 12.

Effect of Peer-Delivered HIVST and STISS on PrEP Adherence

The median follow-up was 11.8 months (IQR 11.0–12.0) per participant, resulting in a total of 932.36 person-months in the intent-to-treat analysis being evaluated. TFV-DP results were available for 90% of study visits (240/268). Overall, the median TFV-DP levels were 147 fmol/punch (IQR 19–603) at month 3, 191 fmol/punch (IQR 0–460) at month 6, 61 fmol/punch (IQR 20–261) at month 9, and 47 fmol/punch (IQR 0–233) at month 12. In the peer delivery and SOC arms, detection of any TFV-DP was 71% and 83%, respectively, at the 3-month visit, 64% and 76% at the 6-month visit, 71% and 83% at the 9-month visit, and 55% and 71% at the 12-month visit (P = 0.04 for all comparisons). The proportion of participants with TFV-DP levels ≥700 fmol per punch at the 3, 6, 9, and 12-month visits was 10%, 5%, 5%, and 0% in the intervention arm and 7%, 15%, 7%, and 2% in the SOC arm, respectively, with no significant differences between arms (P = 0.18).

Of 268 study visits, urine tenofovir results were available for 256 (96%); 12 tests were not conducted. Urine tenofovir testing was conducted at 92% (67/73) of month 3 visits, 96% (65/68) of month 6 visits, 98% (56/57) of month 9 visits, and 97% (68/70) of month 12 visits. PrEP adherence measured by urine TFV levels was 52% (54% and 50%; P = 0.73) at 3 months, 63% (67% and 59%; P = 0.54) at 6 months, 62% (61% and 64%; P = 0.83) at 9 months, and 53% (51% and 54%; P = 0.80) at 12 months in the peer delivery and SOC groups, respectively. At 53% (111/208) of clinic visits where both blood and urine tests were conducted, tenofovir was present in DBS and urine samples for 50.4% (56/111) in the peer delivery arm and 49.6% (55/111) in the SOC arm. There was a strong correlation between tenofovir detection in DBS and urine (P < 0.001; Table 2).

TABLE 2. Tenofovir Detection in DBS and Urine

Tenofovir in Dried Blood Spots	Urine Tenofovir Detection	
Month 3	Month 6	Month 9	Month 12	
Detected (%)	Not Detected (%)	Detected (%)	Not Detected (%)	Detected (%)	Not Detected (%)	Detected (%)	Not Detected (%)	
Any detectable									
 Yes	24 (62)	15 (38)	30 (81)	7 (19)	29 (78)	8 (22)	28 (74)	10 (26)	
 No	0 (0)	11 (100)	0 (0)	14 (100)	0 (0)	11 (100)	3 (14)	18 (86)	
≥700 fmol/punch	7 (100)	0 (0)	7 (88)	1 (12)	5 (100)	0 (0)	1 (100)	0 (0)	
<700 fmol/punch	17 (40)	26 (60)	23 (53)	20 (47)	24 (56)	19 (44)	30 (52)	28 (48)	

The peer-delivered intervention did not affect PrEP adherence when measured by DBS TFV-DP levels over the 12 months (incidence rate ratio [IRR] 0.84; 95% CI: 0.42 to 1.68; P = 0.61) or urine TFV detection (IRR 0.97; 95% CI: 0.86 to 1.09; P = 0.63) (Table 3). Selling sex for survival (IRR 6.93; 95% CI: 2.33, 20.60) and having more than 10 years of schooling (IRR 2.35; 95% CI: 1.14 to 4.84) were associated with PrEP adherence. Paradoxically, a belief that PrEP protects from HIV was associated with a lower likelihood of PrEP adherence (IRR 0.30; 95% CI: 0.14 to 0.68). Age, intimate partner violence, and use of alcohol or marijuana were not associated with PrEP adherence.

TABLE 3. Associations With PrEP Adherence

Participant Characteristic	Incidence Rate Ratio (95% CI)	P	
Randomization arm	
 Control	Ref		
 Intervention	0.84 (0.42 to 1.68)	0.61	
 Age	1.02 (0.89 to 1.17)	0.76	
Education	
 Less than 10 yrs	Ref		
 More than 10 yrs	2.35 (1.14 to 4.84)	0.02	
Experienced intimate partner violence	
 No	Ref		
 Yes	0.79 (0.16 to 3.97)	0.77	
Use of alcohol	
 No	Ref		
 Yes	0.59 (0.17 to 2.01)	0.39	
Selling sex for survival	
 No	Ref		
 Yes	6.93 (2.33 to 20.60)	<0.001	
Believes PrEP protects from HIV	
 Not sure	Ref		
 Very sure	0.30 (0.14 to 0.68)	0.002	
Aware about STISS	
 No	Ref		
 Yes	5.05 (1.99 to 12.83)	0.001	
Use of marijuana	
 No	Ref		
 Yes	2.94 (0.96 to 9.01)	0.059	

Sexual Behavior Outcomes

At enrolment, the median number of receptive anal sex acts in the preceding month was 9 (IQR 4–20), with no significant difference between randomization groups (P = 0.90). In addition, 51% of participants reported condomless sex with intimate partners; this rate remained similar over time at 59%, 45%, 58%, and 47% at 3, 6, 9, and 12 months, respectively, without any noticeable difference between arms (P > 0.10). The self-reported incidence of condomless sex between arms was also comparable (adjusted incidence rate ratio 0.97; 95% CI: 0.91 to 1.04; P = 0.39). No HIV seroconversions were detected in either arm. We observed higher STI incidence among TGW in the peer delivery arm for rectal CT (5.4 versus 3.3 per 100-person years; P = 0.02) and urethral NG (1.0 versus 0.0 per 100-person years; P = 0.01) (Table 4).

TABLE 4. Chlamydia trachomatis and Neisseria gonorrhoeae Incidence

Anatomical Site	Peer Delivery	Standard of Care	P	
Chlamydia trachomatis (incidence per 100 person-years)	
 Rectal	5.4	3.3	0.02	
 Urethral (urine)	2.9	1.3	0.08	
 Oropharyngeal	0.6	0.7	1.00	
Neisseria gonorrhoeae (incidence per 100 person-years)	
 Rectal	3.1	3.3	1.00	
 Urethral (urine)	1.0	0.0	0.01	
 Oropharyngeal	0.6	1.1	0.46	

DISCUSSION

In this pilot cluster randomized trial, peer delivery of HIV self-tests, STI self-collection kits, and oral PrEP was feasible and acceptable to transgender women in Uganda. Most participants reported that they received the self-tests and self-collection kits from their peers and returned the samples, which indicates a high level of feasibility. Acceptability was also high because most participants used HIVST for testing themselves and self-sampling kits for specimen collection. Around 75% had detectable tenofovir levels in their urine and blood, indicating that some PrEP use had occurred. However, overall PrEP drug concentrations were low, suggesting that most did not take their medication according to prescription. Finally, there was no intervention effect on PrEP adherence or sexual risk behaviors despite near universal use of HIVST and STI self-sampling. Notably, there were no HIV seroconversions, despite the incident STI, emphasizing the necessity of PrEP for this population.

In our study, adherence to PrEP was consistently low over the twelve-month trial period as assessed by quantitative TFV DP levels in DBS, suggesting a lack of prevention-effective adherence.41 Detectable tenofovir levels were significantly higher in the SOC group, suggesting that those who continued to attend clinic appointments were motivated to take PrEP. Fewer than 10% of TGW had protective tenofovir concentrations (ie, consistent with at least 4 doses per week). In the iPrEx open-label extension study, similar results were observed among 151 TGW, of whom 15% had drug levels corresponding to taking 4–6 pills per week for protection.42 In comparison, a study of 25 TGW in Brazil revealed that protective concentrations of tenofovir (≥700 fmol per punch) were observed in 17 (68%) at week 12, 15 (60%) at week 24, 12 (48%) at week 36, and 13 (52%) at week 48.43 Studies conducted in California found that approximately half of TGW had protective drug levels.44,45 A study in Kenya found protective drug levels in 3 of 8 TGW (38%).46 Our previous research indicated that TGW were 4 times as likely to adhere to PrEP as cisgender female sex workers47; however, this result was not reproduced in the current trial. The lack of longitudinal PrEP adherence data for transgender individuals in sub-Saharan Africa is a notable gap.48 Further research is needed to effectively implement PrEP and fully use its potential for African TGW, including use of long-acting formulations.

Peer delivery of self-collection kits for CT and NG testing was feasible for TGW, who found chlamydia and gonorrhea self-sampling to be highly satisfactory and easy to perform. Our qualitative research within this cohort revealed that self-sampling empowered TGW to take the initiative concerning their STI testing and avoid the awkwardness of showing their bodies to health care professionals. Their desire for privacy and confidentiality further motivated them to participate in STI testing and receive treatment.22 These results are consistent with studies conducted in Brazil and Thailand that found a high degree of acceptability for self-sampling for STI testing.9,10 The WHO recommends self-collection of samples to enable STI testing for key populations. To date, however, no published studies to the best of our knowledge have assessed peer delivery of STI self-collection kits for TGW in sub-Saharan Africa. To extend the reach of STI testing for underserved populations such as TGW, task shifting to peers and other lay providers seems highly impactful.

Nearly all participants in our study reported using HIVST, with most exhibiting confidence in teaching others how to self-test and almost everyone recommending it to family and friends. The WHO recommends HIVST as a discreet and empowering prevention tool that promotes autonomy among clients while increasing testing coverage for those not reached by traditional testing services.13 Our results corroborate a previous study of 44 TGW in Burundi, which reported that all used self-tests and 80% of HIVST users were first-time testers.49 Studies from Asia have indicated that community-based HIVST for TGW was acceptable and feasible, even during the COVID-19 pandemic.50–53 Similarly, our research was conducted during the pandemic, when public health mitigation efforts limited access to public transportation and highlighted the importance of decentralized services such as peer-delivered HIVST and oral PrEP. Differentiated service delivery models can potentially remove barriers to PrEP access and should be optimized in future studies for improved uptake, persistence, and effective use.54 Finally, this was one of the first studies to use point-of-care urine TFV tests in sub-Saharan Africa, demonstrating the feasibility and correlation of urine TFV test results with TFV DP DBS results.

To the best of our knowledge, the current research is the first to assess peer-delivered HIV self-tests, STI self-sampling, and oral PrEP for TGW in sub-Saharan Africa. Despite the difficulties created by COVID-19 pandemic restrictions, we achieved good retention among TGW by using a community-engaged approach to intervention delivery, capitalizing on peer support, and conducting virtual and home visits. Significantly, no adverse effects from participating in the research were identified. Despite these strengths, our study also has limitations. Some participants were unsatisfied with their designated peer and were allowed to switch within the same randomized group, potentially introducing the possibility of contamination and limiting cluster size. Despite this possibility, contamination would not have affected the null results of the trial, as PrEP adherence was low regardless of the randomization group. Use of HIVST and STISS was self-reported and subjects to social desirability and recall bias. In addition, white coat dosing (ie, PrEP use only before the visit due to social desirability bias) may have occurred due to knowledge that urine tenofovir testing would be conducted during clinic visits. Nevertheless, the TFV-DP levels in DBS indicated low PrEP adherence over time. Finally, detecting NG in only 4 urine samples affected the convergence of regression models.

CONCLUSIONS

Our cluster randomized trial revealed that peer-delivered HIVST and STI self-sampling did not affect PrEP adherence among transgender women in Uganda. However, this study did demonstrate the feasibility of combination HIV prevention delivery through peers, as HIVST and STI self-sampling were well-accepted and frequently used for self-testing and specimen collection. Despite the availability of these services, PrEP adherence was still low, thus potentially not providing adequate protection against HIV infection. To increase PrEP use in this population, it is necessary to consider choice-based delivery models incorporating long-acting forms of PrEP, alternative delivery methods, and trans-friendly care options.

AI tools: Grammarly and WriterBuddy were used to improve the readability and phrasing and proofread the manuscript.

ACKNOWLEDGMENTS

The authors are grateful to the study participants for their participation and dedication. The authors thank the study team members, including TGW peers, for their contributions to data collection. The authors thank Transgender Equality Uganda for their support of this project.

The research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under Grant Number R34MH121084 to A.M. A.M. received research funding outside the submitted work from Gilead Sciences, Inc. J.E.H. is a consultant for Merck. None of the remaining authors declared any conflict of interest.

These data were reported, in part, at the 18th International Conference on HIV Treatment and Prevention Adherence, June 11–13, 2023; Fajardo, Puerto Rico, USA (abstract #1207).

The authors have no funding or conflicts of interest to disclose.

A.M. and J.E.H. designed the study. M.G. donated urine tenofovir tests. A.M. wrote the first draft. R.N. performed the statistical analyses. All authors contributed to data collection, interpretation of the results, and manuscript writing and approved the final draft.

The authors designed and conducted the study, had full access to the raw data, performed all analyses, wrote the manuscript, and had final responsibility for the decision to submit for publication. The funder had no role in the study's design, data collection, analysis, interpretation, or report writing. This paper represents the opinions of the authors and does not necessarily reflect the official views of the National Institutes of Health.
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