Abstract
Background:
HIV self-testing (HIVST) and pre-exposure prophylaxis (PrEP) are complementary tools that could empower sex workers to control their HIV protection, but few studies have jointly evaluated PrEP and HIVST in any setting.
Methods:
The Empower Study was an open-label randomized trial in Uganda. Sex workers were offered F/TDF and randomized 1:1 to monthly HIVST and quarterly in-clinic testing (intervention) or quarterly in-clinic HIV testing alone (standard-of-care) and followed for 12 months. PrEP adherence was measured using electronic adherence monitoring and tenofovir diphosphate (TFV-DP) levels in dried blood spots. Adherence outcomes and sexual behaviors were compared by arm using generalized estimating equation models.
Results:
We enrolled 110 sex workers: 84 cisgender women, 14 transgender women, 10 men who have sex with men and two transgender men. Median age was 23 years. Twelve-month retention was 75%. Nearly all (99.4%) used ≥1 HIVST kit. The proportion with TFV-DP levels ≥700 fmol/punch in the HIVST and SOC arms at the 3, 6, 9 and 12-month visits was 2.4%, 2.3%, 0%, and 0% and 7.9%, 0%, 0%, and 0%, respectively, with no differences by randomization arm (p>0.2). Self-reported condomless sex with paying partners was similar by arm (adjusted incidence rate ratio [aIRR] 0.70; 95% CI: 0.42–1.17; p=0.18). One seroconversion occurred (HIV incidence, 0.9/100 person-years); TFV-DP was not detected at any visit.
Conclusions:
A gender-diverse sample of sex workers in Uganda used HIVST but not daily oral PrEP for HIV protection. Alternate approaches to promote PrEP use, including long-acting formulations, should be considered in this population.
Keywords: HIVST, PrEP, Adherence, Sex Worker, Africa
INTRODUCTION
Globally, cisgender women, cisgender men, and transgender sex workers are 49, 21, and 14 times as likely, respectively, to be living with HIV as other adults in the general population [1]. Yet, sex workers are less likely than the general population to engage with HIV services because of concerns about sex work criminalization, entrenched social stigma, and discrimination from health workers [2, 3]. Additionally, condom use is often difficult to negotiate or results in less income generation [4], highlighting the need for additional HIV prevention approaches. Empowering sex workers to utilize combination HIV prevention interventions could help decrease HIV acquisition in this vulnerable population. HIV self-testing (HIVST) and tenofovir-based oral pre-exposure prophylaxis (PrEP) are evidence-based, self-controlled HIV prevention tools, but they are currently not well utilized by sex workers [5, 6]. Moreover, these tools could be employed with their paying and nonpaying (intimate) sexual partners to maximize impact.
Several features of HIVST and PrEP may be particularly attractive for sex workers. HIVST, a process in which an individual performs an HIV rapid diagnostic test and interprets the result independently [7], is highly acceptable with users appreciating its convenience and discretion [7–9], and is recommended by the World Health Organization (WHO) [10]. HIVST can empower those who may otherwise not test, or test as frequently, by providing autonomy, freedom, and control over testing decisions [11]. Moreover, HIVST reaches people at high risk of HIV and may be an important entry point for PrEP, which may similarly empower the user [12]. The effectiveness of PrEP, however, is highly dependent on adherence, which has been challenging for many, including sex workers [13, 14]. HIVST and PrEP are potentially complementary tools that could be combined to empower sex workers to prevent HIV acquisition, but few studies have jointly evaluated PrEP and HIVST in any setting.
Limited data are available regarding whether joint HIVST and PrEP delivery could increase PrEP adherence and reduce sexual risk behaviors among sex workers. Although variable by population, condom use increased, and diagnoses of sexually transmitted infections (STI) decreased in prior PrEP studies, suggesting PrEP use can be synergistic with other prevention methods [15]. To test if combination HIVST and PrEP influenced uptake and use of each prevention intervention, we conducted a randomized trial among HIV-negative cisgender women, cisgender men, and transgender sex workers initiating PrEP in Uganda. We hypothesized that joint HIVST and PrEP delivery could be empowering through combined use of both interventions.
METHODS
Trial Design
The Empower Study was an open-label randomized trial conducted in Kampala, Uganda (NCT03426670). Cisgender women (female sex workers; FSW), cisgender men who have sex with men (MSM), and transgender sex workers (TGSW) (N=110) were offered oral PrEP (co-formulated emtricitabine/tenofovir disoproxil fumarate; FTC/TDF) and individually randomized 1:1 to receive monthly HIVST and quarterly in-clinic testing (intervention) or quarterly in-clinic HIV testing alone (standard-of-care; SOC). Blinded allocation to study arm was performed by research nurses using REDCap electronic data capture tools [16, 17]. Study participants and research staff were not blinded to intervention assignment. There were no significant protocol changes after trial commencement. The study objectives were to test the effect of HIVST in addition to clinic-based testing alone on: 1) PrEP adherence and 2) sexual behaviors. Additionally, we qualitatively explored how HIVST and PrEP influenced prevention uptake among sex workers and their partners [18]. Study data were reviewed by an independent data monitoring committee. Intervention design was informed by Protection Motivation Theory [19, 20]. This trial is reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) statement [21].
Population and Procedures
The Empower Study involved sex workers; estimated HIV prevalence among FSW in Kampala was 37% in 2016 [22]. Data for MSM and TGSW are not available. Participants were enrolled using peer recruiters between June 7, 2018, and January 10, 2019, and followed for 12 months. The trial ended on January 31, 2020. Participant gender was self-identified. At study entry, sex workers were 18 years of age or older, received money or goods in exchange for sexual services, tested negative for HIV and Hepatitis B virus (HBV), were willing to take PrEP, were willing and able to comply with study procedures, and had adequate renal function (creatinine clearance ≥60ml/min). Research nurses taught sex workers in the HIVST arm how to use OraQuick® rapid HIV-1/2 self-test kits (OraSure Technologies, USA). At each quarterly visit, they received four HIVST kits; two for own use and two for testing sexual partners. At the time of the study, HIVST kits were only available through research studies. All study participants received quarterly in-clinic HIV rapid testing as SOC. Oral PrEP was provided to all participants, who received three bottles each with a one-month supply of co-formulated emtricitabine 200mg/tenofovir disoproxil fumarate 300mg (FTC/TDF). Participants in the HIVST arm were instructed to self-test before starting each monthly course of PrEP, during the two-month period between scheduled quarterly study visits. Adherence to PrEP was measured using Wisepill devices for electronic adherence monitoring (EAM) (Wisepill Technologies, South Africa); these devices are smart pill containers that record a date-and-time stamp for each opening as a proxy for pill ingestion. Dried blood spot samples (DBS) were also collected quarterly for detection and quantification of tenofovir diphosphate (TFV-DP) levels [23]. Data on PrEP adherence and sexual risk behaviors were collected during monthly live phone interviews and quarterly in-person visits, including validated socio-behavioral scales for stigma (HIV stigma scale [24]) and problematic alcohol use (RAPS-4 scale [25]). Participants were screened for depression using the Patient Health Questionnaire [26]; those with PHQ-9 scores ≥10 were escorted to the Infectious Diseases Institute mental health clinic, if desired. Study interactions occurred in English or Luganda (local language). All participants were offered additional HIV prevention services including individualized HIV and PrEP counseling, condoms and lubricant; other forms of contraception (FSW only); and free STI screening and treatment (as SOC per national guidelines [27]. All participants were clinically monitored for adverse events. Each received an IRB-approved reimbursement of UGX 30,000 (USD 7.86).
Laboratory Methods
Sex workers were tested for HIV using serial rapid tests according to national guidelines [28]. HBV testing was performed using Pal® HBsAg rapid tests (Healgan Scientific, Houston, TX). Serum creatinine testing was performed using a Cobas Integra 400 biochemistry analyzer (Roche, Germany). Creatinine results were available within 72 hours; abnormal values were flagged, and participants contacted for clinical management. Intracellular TFV-DP concentrations were quantified from DBS tested in batch at the University of Cape Town Clinical PK Laboratory, South Africa using validated liquid chromatography/tandem mass spectrometry methods [29].
Statistical Analysis
The primary outcome was PrEP adherence as measured by EAM (number of days with recorded device openings divided by number of days with device detected as active) [30] and TFV-DP levels in DBS (≥700 fmol per punch). We restricted device openings to one per day to avoid misclassification of adherence from multiple openings (e.g., due to curiosity or device use for other medications). A secondary adherence measure was pharmacy refill (proportion of expected pills taken). Chi-square tests and one-way analysis of variance (ANOVA) models were used to compare outcomes by randomization arm. Correlations of adherence measures were calculated using paired sample t-tests and tests of significance were performed using Fisher exact test. We used an intent-to-treat approach (analyzed all participants regardless of PrEP refills) to compare adherence outcomes by randomization arm using a generalized estimating equations (GEE) model using repeated measures with identity link, exchangeable correlation structure and robust variance estimates. The trial had 80% power to detect a 17–23% increase in PrEP adherence resulting from use of HIVST with a sample size of 110 sex workers assuming a standard deviation of 30–40%, 10% loss to follow-up, and a two-sided alpha of 0.05. Secondary outcome measures were self-reported: a) condomless sex acts and b) acceptability of HIVST (assessed by HIVST kit usage and experiences). We used zero-inflated Poisson regression to assess condom use with paying and nonpaying partners because the distribution of sex acts was overdispersed relative to the Poisson distribution (i.e., conditional variance was larger than the conditional mean) [31]. Covariates included baseline demographics including age, gender, marital status, level of education, duration of sex work and problematic alcohol and drug use and were independently tested for associations with outcomes. Analyses were adjusted a priori for gender. We used Spearman’s correlation to evaluate the relationship between EAM and TFV-DP levels in DBS. Statistical analyses were performed using Stata 14 (StataCorp, College Station, TX, USA).
Ethics Approval
The study was approved by the Higher Degrees Research Ethics Committee, Makerere University School of Public Health (HDREC 500), Partners Human Research Committee/Massachusetts General Hospital (2017/P001951/PHS), Uganda National Council for Science and Technology (SS 4467) and National Drug Authority (CTA 0046). Each participant provided written informed consent.
RESULTS
Population Characteristics
We screened 136 sex workers and enrolled 117; reasons for non-participation are shown in Figure 1. Seven participants who emigrated or lost interest in the study within one month of study entry were disenrolled (three in the HIVST arm and four in the SOC arm). The final study sample was 110 sex workers (57 in the HIVST arm and 53 in the SOC arm) with <10% difference in socio-demographic characteristics between arms (Table 1). Of these, 84 were FSW, 14 were transgender women (TGW), 10 were MSM, and two were transgender men. The median age was 23 years (interquartile range [IQR] 20–28). Eighty-eight (80%) were single; sex work was the main source of income for 75 (68%). Sixty-nine (63%) had at least one child. Median age at onset of sex work was 19 years (IQR 17–23); median monthly income was UGX 400,000 (USD 104.77). Median charge for vaginal and anal sex was UGX 20,000 and UGX 125,000 (USD 5.18 and USD 32.38) without a condom, and UGX 5,000 and UGX 50,000 shillings (USD 1.30 and USD 12.95) with a condom, respectively. At baseline, 95 (86.4%) had heard about PrEP. Most (N=88; 80.0%) were worried about getting HIV, 87 (79.1%) believed that PrEP could prevent them from getting HIV, and 66 (60.0%) were worried about PrEP side effects. Participation retention (completed study visits) was 67% and 75% at 6 and 12 months, respectively. Twelve-month visit completion was 81% and 70% in the HIVST and SOC arms, respectively, with no differences by arm (p=0.19). Overall, 12-month retention was 90% for MSM, 81% for TGSW, and 73% for FSW.
Figure 1:
Trial Profile
Table 1:
Baseline Characteristics by Randomization Arm
| Characteristic | HIVST (N=57) N (%) or Median (IQR) |
SOC (N=53) N (%) or Median (IQR) |
|---|---|---|
| Gender | ||
| Female | 39 (68.4) | 45 (84.9) |
| Male | 7 (12.3) | 3 (5.7) |
| Transgender | 11 (19.3) | 5 (9.4) |
| Age | 23.1 (20.9–28.9) | 22.2 (20.4–25.1) |
| 18 – 24 | 32 (56.1) | 33 (62.3) |
| 25 – 29 | 14 (24.6) | 12 (22.6) |
| 30 – 34 | 7 (12.3) | 4 (7.6) |
| >35 | 4 (7.0) | 4 (7.5) |
| Completed years of education | 7 (3–10) | 9 (6–11) |
| 0 | 3 (5.3) | 11 (20.7) |
| 1 – 7 | 19 (33.3) | 18 (34.0) |
| 8 – 11 | 25 (43.9) | 17 (32.1) |
| ≥12 | 10 (17.5) | 7 (13.2) |
| Marital status | ||
| Divorced/separated/widowed | 10 (17.5) | 9 (17.0) |
| Married | 1 (1.8) | 2 (3.8) |
| Single with a nonpaying partner | 20 (35.1) | 21 (39.6) |
| Single without nonpaying partner | 26 (45.6) | 21 (39.6) |
| Number of children | ||
| None | 26 (45.6) | 15 (28.3) |
| 1 – 2 | 19 (33.3) | 29 (54.7) |
| ≥3 | 12 (21.1) | 9 (17.0) |
| Average monthly income (UGX) | 300,000 (150,000–500,000) | 300,000 (200,000–600,000) |
| Sex work main source of income | ||
| Yes | 37 (64.9) | 38 (71.7) |
| No | 20 (35.1) | 15 (28.3) |
| Age at onset of sex work [n= 108] | 19 (17 – 25) | 19 (17 – 22) |
| Sexual partners in prior month | 60 (20–140) | 80 (30–100) |
| Average charge for vaginal sex with a condom [n= 84] | 5,000 (5,000–10,000) | 8,000 (5,000–10,000) |
| Average charge for vaginal sex without a condom [n=49] | 30,000 (10,000–50,000) | 20,000 (20,000–30,000) |
| Average charge for anal sex with a condom [n=30] | 50,000 (20,000–70,000) | 30,000 (30,000–50,000) |
| Average charge for anal sex without a condom [n=26] | 50,000 (20,000–150,000) | 50,000 (32,500–90,000) |
| Currently smoking tobacco | 6 (10.5) | 5 (9.4) |
| Currently using other recreational drugs | 10 (17.5) | 9 (17.0) |
| Possible depression1 | 24 (42.1) | 21 (39.6) |
| Problematic alcohol use2 | 32 (56.1) | 30 (56.6) |
| Sex work stigma3 | 52 (91.2) | 48 (92.5) |
The Patient Health Questionnaire (PHQ-2), which has been validated in Uganda [26], was used to assess depression; a response of “yes” to either question is considered possible depression.
Alcohol use was assessed using the RAPS-4 scale [25]; a response of “yes” to one or more questions is considered problematic alcohol use in the prior year.
Stigma was assessed using the HIV stigma scale [24]; data indicate a response of agree or strongly agree
HIV Self-Testing
In a visit-level analysis among intervention participants (n=161/228 possible visits), the proportion of sex workers in the HIVST arm who self-reported using ≥1 kit was 99.4% (160/161) overall with 97.4% (38/39), 100% (40/40), 100% (39/39), and 100% (43/43) at the 3, 6, 9, and 12-month visits, respectively. Additionally, 158 (98.1%) believed that the kit gave an accurate result, 154 (95.7%) said the kit was very easy to use, and 133 (82.6%) preferred to self-test at home by themselves compared to clinic-based testing. A minority (N=45; 27.9%) tested at least once with someone else including paying partners (22; 48.9%), nonpaying partners (16; 35.6%) and family members (3; 6.7%). At the 161 visits, 99 (61.8%) reported using the HIVST kit before opening a new PrEP bottle and 93 (57.8%) reported HIVST use before sex with a paying partner. All (100%) said they felt confident enough to show somebody else how to use HIVST kits, and 159 (98.8%) said they would recommend HIVST to friends and relatives. Secondary distribution of HIVST kits to paying and nonpaying partners of sex workers in the intervention arm was reported at 71 (44.1%) and 51 (31.7%) visits.
Effect of HIVST on PrEP Adherence
Median follow-up was 11.1 months (interquartile range (IQR) 11.0, 11.3) per participant. We evaluated 1,072 person-months in the intent-to-treat analysis. Eight participants (14%) in the HIVST arm and 18 (34%) in the SOC arm told research staff they had permanently stopped taking PrEP during the study. Overall, mean adherence by EAM was 25.9% (30.9% and 20.6%; p=0.047) at 6 months and 17.2% (22.1% and 11.5%; p=0.052) at 12 months in the HIVST and SOC arms, respectively (Figure 2). By arm, any TFV-DP detection was 21% and 21% at the 3-month visit, 21% and 25% at the 6-month visit, 14% and 11% at the 9-month visit, and 20% and 10% at the 12-month visits (p>0.2 for all comparisons). The proportion with TFV-DP levels ≥700 fmol per punch in the HIVST and SOC arms at the 3, 6, 9 and 12-month visits was 2.4%, 2.3%, 0%, and 0% and 7.9%, 0%, 0%, and 0%, respectively, with no differences by randomization arm (p>0.2). Similar findings were observed when adherence was measured by pharmacy refill at the 3, 6, 9 and 12-month visits (p>0.1 for all comparisons). As shown in Figure 3, the correlation between EAM and DBS had a rho of 0.212 overall (0.240 in the HIVST arm and 0.193 in the SOC arm; p=0.04 for the randomized groups). No intervention effect was observed on PrEP adherence by randomization arm over the 12-month period as measured by EAM (adjusted odds ratio [aOR] 3.32; 95% CI: −5.3–11.9; p=0.45) or DBS TFV-DP levels (aOR 1.01; 95% CI: 0.91–1.97; p=0.98) (Table 2).
Figure 2: PrEP adherence by EAM and TFV-DP levels in DBS.
EAM (electronic adherence monitoring); TFV (tenofovir); HIVST (HIV self-testing arm); SOC (standard of care arm)
Figure 3:
Correlation of PrEP adherence by electronic adherence monitoring and TFV-DP levels in DBS
Table 2:
Effect of HIV Self-Testing on PrEP Adherence
| PrEP adherence | N (%) | Odds Ratio (OR; 95% CI) |
P | Adjusted OR (95% CI) |
P |
|---|---|---|---|---|---|
| EAM | |||||
| SOC | 42 (54%) | Ref | Ref | ||
| HIVST | 36 (46%) | 2.83 (−5.9, 11.7) | 0.53 | 3.32 (−5.3, 11.9) | 0.45 |
| EAM (by gender) | |||||
| FSW | 58 (75) | Ref | Ref | ||
| MSM | 8 (10) | 0.58 (−13.3–14.5) | 0.94 | −0.15 (−13.8–13.5) | 0.98 |
| TGSW | 12 (15) | −4.18 (−17.4–9.1) | 0.54 | −4.98 (−17.6–7.8) | 0.45 |
| TFV-DP levels in DBS (by arm) | |||||
| SOC | 46 (53) | Ref | Ref | ||
| HIVST | 40 (47) | 1.22 (0.52, 2.89) | 0.65 | 1.01 (0.44, 2.35) | 0.98 |
| TFV-DP levels in DBS (by gender) | |||||
| FSW | 63 (74) | Ref | Ref | ||
| MSM | 9 (10) | 1.36 (0.28–6.51) | 0.7 | 1.35 (0.29–6.28) | 0.69 |
| TGSW | 14 (16) | 4.00 (1.54–10.35) | 0.004 | 3.99 (1.58–10.05) | 0.003 |
EAM (electronic adherence monitoring); TFV-DP (tenofovir diphosphate levels); DBS (dried blood spots)
Effect of HIVST on Sexual Risk Behaviors
At baseline, the mean number of sexual partners in the prior month was 72 (range 30–120). Most (N=67; 61%) had intimate partner(s) and 51 (76%) reported never using condoms with intimate partners. Sixty-eight percent did not disclose sex work to their intimate partners. Overall, we observed no difference in self-reported condomless sex with paying partners by randomization arm (adjusted incidence rate ratio [aIRR] 0.70; 95% CI: 0.42–1.17; p=0.18).
Subgroup analyses
We observed an apparent intervention effect on PrEP adherence in the small subset of 16 TGSW: EAM (aOR 3.86; 95% CI: 1.15–12.9 p=0.006) and DBS TFV-DP levels (aOR 3.99; 95% CI: 1.58–10.05; p=0.003). An intervention effect on sexual risk behaviors was observed among MSM (aIRR 0.11; 95% CI: 0.06–0.20; p<0.001) and TGSW (aIRR 0.18; 95% CI: 0.10–0.32; p=0.001) were less likely to report condomless sex with paying partners than FSW regardless of randomization arm. Similar findings were observed for condom use with nonpaying partners with no difference by arm (aIRR 0.98; 95% CI: 0.70–1.39; p=0.93), but with MSM less likely to report condomless sex (aIRR 0.01; 95% CI: 0.00–0.05; p<0.001) than FSW.
Adverse Event Profile and HIV Acquisition
No serious adverse events were identified as related to study participation or PrEP. We detected one seroconversion in the HIVST arm at the 9-month visit (HIV incidence, 0.9 per 100 person-years). Tenofovir was not detected in DBS at the 3, 6 or 9-month visits, and drug resistance testing was not performed because the FSW participant did not return for her post-seroconversion visit. She was encouraged to start antiretroviral treatment but repeatedly declined.
Discussion
In this randomized trial of HIVST co-distributed with PrEP, PrEP adherence was low despite near universal reported use of HIVST among cisgender women, cisgender men, and transgender sex workers in Uganda. The lack of intervention effect was consistent when PrEP adherence was assessed using electronically monitored adherence and tenofovir concentrations in dried blood spot samples. EAM-assessed adherence was significantly higher in the HIVST arm at the 6-month visit, but this was not sustained during the 12-month study period. HIVST acceptability was high as nearly all sex workers used the kits to test themselves, and half distributed HIVST kits to paying and nonpaying partners. Self-reported condomless sex with paying and nonpaying partners decreased among MSM and TGSW but not FSW regardless of study arm. HIV incidence was low; only one seroconversion occurred (and this event occurred in the absence of PrEP use). In sub-group analyses, TGSW were four times as likely to adhere to PrEP as FSW suggesting possible gender differences. However, the small numbers of TGSW may result in an overestimation of the intervention effect.
Our results are consistent with those of other sex worker studies in sub-Saharan Africa in which oral PrEP was infrequently taken at levels sufficient to achieve HIV protection [32–34]. We found that despite continual engagement in sex work during the study, PrEP use was suboptimal during this risk period suggesting a lack of prevention-effective adherence [35]. PrEP is an empowering self-controlled prevention tool that allows sex workers to control their HIV protection without requiring the consent of their partners [36]. Our published qualitative work in this cohort [18] found that combined HIVST and PrEP use enabled sex workers to overcome physical and emotional barriers to intimacy, preserve relationships with their intimate partners, and avoid the stigma and inconvenience experienced when testing at public health facilities, which empowered them to protect their sexual health. Recent work among young women in Kenya found that HIV risk perception was dynamic, evolved as partnerships and sexual behaviors changed, and influenced PrEP and condom use over time [37]. The dynamic nature of HIV risk perception may have influenced PrEP persistence and could explain the misalignment between perceptions that PrEP was empowering and suboptimal PrEP adherence in our study.
At least four doses per week are required to provide HIV protection following rectal exposure; higher adherence is likely required for vaginal exposure [38, 39]. Second generation PrEP drugs, including the dapivirine vaginal ring and injectable cabotegravir (CAB LA), are dosed at least monthly which provides an adherence advantage over daily dosing [40, 41]. However, concerns about side effects and HIV stigma may still limit uptake of long-acting PrEP. The HIV Prevention Trials Network 083 and 084 studies demonstrated that CAB LA is a well-tolerated and effective injectable PrEP drug for cisgender women, MSM, and TGW [40, 42]. Other long acting PrEP agents, including islatravir and lenacapavir, are under evaluation [43–45]. Future studies should evaluate optimal approaches to motivate high uptake and sustained use of long-acting PrEP formulations among sex workers.
Nearly all sex workers in our study reported using HIVST, half gave kits to paying or nonpaying partners, and one-in-four self-tested with a partner. HIVST is a self-controlled prevention tool that could empower sex workers to negotiate condom use. Sex workers use point-of-sex testing (i.e., using HIVST kits to screen paying partners) as a risk reduction strategy in settings where partners pay more for condomless sex [18, 46–48]. Studies of FSW, MSM, and TGSW suggest that point-of-sex testing empowers and informs sexual decision making such as avoiding sex or insisting on condom use with paying partners who tested HIV-positive [11, 49–51]. This ancillary benefit could motivate HIVST use among sex workers. However, some caution regarding the utility of HIVST for sexual decision making is warranted; oral fluid self-test kits may be misinterpreted and have low sensitivity in acute HIV infection, and in persons taking PrEP or ART, which may result in false-negative results and a false sense of safety [18, 52, 53].
We found no evidence of behavioral risk compensation among sex workers in agreement with previous reports [54, 55]. We observed a lower likelihood of sex unprotected by condoms among MSM and TGSW but not FSW in contrast with previous studies [56]. In our study, the median charge for anal sex with a condom was 2.5-fold higher than for condomless vaginal sex, suggesting financial motivations to engage in condomless sex may have been less compelling for MSM and TGSW than FSW. A meta-analysis of 17 studies with 6,671 MSM found that PrEP use was associated with a significant increase in condomless sex and STI diagnoses outside of sex work [57]. The association between PrEP and STI incidence is less clear for TGSW, and programmatic data are lacking.
Subgroup analyses revealed a higher likelihood of PrEP adherence among TGSW. This finding may be explained by motivation to access HIV prevention services for a marginalized population that had previously not participated in a clinical trial in Uganda. PrEP adherence among TGSW in sub-Saharan Africa is poorly studied, offering few data for comparison. South African TGW reported decreased HIV risk, HIV protection in the event of rape, and being in control of one’s health as reasons for taking PrEP [58]. Other work in Kenya (n=53) found that TFV-DP was detected in 62.5% of TGW vs 17.7% of MSM at the six-month visit. In that study, PrEP use was motivated by unplanned or frequent risky sexual behavior and desire to remain HIV-negative [59]. Ongoing studies in Uganda (ClinicalTrials.gov NCT04328025, 04867798 and 04491422) will contribute to the knowledge base regarding HIVST and PrEP use in this population.
The present study is the first, to our knowledge, to evaluate HIVST and PrEP use among a gender-diverse sample of sex workers in sub-Saharan Africa. We achieved good retention among MSM and TGSW in Uganda, by establishing strong community linkages, leveraging peer support, and providing research staff with gender sensitivity training. Importantly, no social harms related to research participation were identified. In addition to these strengths, our study has limitations. One quarter of the study sample was lost to follow-up, but dropout rates did not differ by study arm. We enrolled a small sample of MSM and TGSW; the gender differences we observed should thus be interpreted with caution. HIVST was only available through research programs at the time of the study, and intervention arm participants may have shared kits with the SOC group. Nevertheless, any such contamination would not have impacted the null results of the trial, as PrEP adherence was poor irrespective of randomization group. Additionally, misclassification of device non-use due to stigma may have occurred [60]. However, TFV-levels in DBS demonstrated similarly poor PrEP adherence.
In conclusion, our randomized trial found no benefit for HIVST in supporting PrEP adherence among sex workers in Uganda. Acceptability of HIVST was high with frequent use of this prevention tool for self-testing and testing with sexual partners. PrEP adherence was low and insufficient for HIV protection. Future studies should evaluate alternate strategies to promote sustained use of PrEP for sex workers in sub-Saharan Africa, including long-acting PrEP formulations.
Supplementary Material
Table 3.
Effect of HIV Self-Testing on Sexual Behaviors
| Sexual Risk Behaviors | N (%) or Median (IQR) |
Incidence rate ratio (IRR; 95% CI) |
P | Adjusted IRR (95% CI) |
P |
|---|---|---|---|---|---|
| Age | 22.8 (20.4 – 27.6) | 1.00 (0.97, 1.02) | 0.82 | 0.99 (0.96, 1.03) | 0.70 |
| Transgender | 16 (15) | 0.16 (0.09, 0.27) | 0.01 | 0.18 (0.10, 0.32) | <0.001 |
| Duration of sex work | 3.1 (1.7 – 4.8) | 1.00 (0.97, 1.03) | 0.85 | 1.02 (0.97, 1.07) | 0.51 |
| Problematic alcohol use | 62 (56) | 0.90 (0.48, 1.67) | 0.73 | 0.81 (0.46, 1.45) | 0.48 |
| Condom use, paying partners (by arm) | 70 (24 – 126) | 0.78 (0.49, 1.27) | 0.29 | 0.70 (0.42, 1.17) | 0.18 |
| Condom use, nonpaying partners (by arm) | 11 (5 – 23) | 1.07 (0.3, 1.58) | 0.73 | 0.98 (0.70, 1.39) | 0.93 |
| TGSW | 16 (15) | 0.16 (0.09, 0.27) | 0.01 | 0.18 (0.10, 0.32) | <0.01 |
| TGSW | 16 (15) | 1.68 (1.38, 2.04) | <0.01 | 1.55 (0.81, 3.00) | 0.19 |
Acknowledgements
We are grateful to the study participants for their participation and dedication. We thank the study team members at the research site for their contributions to data collection.
Funding source:
This work was supported through research grants from National Institutes of Health [research grant number K43 010695 (AM) and K24 Mentor Award MH114732 (JEH). This research was funded in part by a 2017 developmental grant to AM from the University of Washington / Fred Hutch Center for AIDS Research, an NIH funded program under award number AI027757 which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, NIDDK. This paper represents the opinions of the authors and does not necessarily represent the official views of the National Institutes of Health.
Role of the funding source:
The authors designed and executed 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 study design, data collection, analysis, interpretation or writing of the report.
Conflicts of interest/competing interest
AM received donated FTC/TDF from Gilead Sciences for this investigator-sponsored study and served as an advisor for ViiV Healthcare. JMB served as an advisor for Gilead Sciences, Janssen, and Merck. JEH is a consultant for Merck.
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