Suppressed HIV antibody responses following exposure to antiretrovirals—evidence from PrEP randomized trials and early antiretroviral treatment initiation studies

Abstract

Background:

Exposure to antiretrovirals at or early after HIV acquisition can suppress viral replication and blunt antibody (Ab) responses; a reduced HIV detectability could impact diagnosis and blood donation screening.

Methods:

We used three antigen (Ag)/Ab assays and one nucleic acid test (NAT) to analyze samples collected in pre-exposure prophylaxis (PrEP) trials (iPrEx; Partners PrEP) before infection detection by Ab-only rapid diagnostic tests (RDTs), and in early antiretroviral treatment (ART) initiation studies (RV254; SIPP).

Results:

Reactivity using NAT and Ag/Ab assays in samples collected up to 8 weeks prior to the first reactive RDT from 251 PrEP trials participants varied between 49–61% for active PrEP users and between 27–37% for placebo users. Among RV254 participants, reactivity in Ag/Ab assays was <100% at all timepoints, and lower among those initiating ART earlier. Seroreversions occurred for 29% (16/55), and blood donation screening with NAT and Ag/Ab assays could have missed up to 36% (20/55) of RV254 participants. For SIPP participants, who started ART at later timepoints, Ag/Ab assays identified infections with no evidence of reactivity waning.

Conclusion:

PrEP and early ART initiation can delay or reduce HIV detectability. Considerations for the implementation of NAT and Ag/Ab tests in PrEP/PEP programs relying on Ab-only RDTs should be balanced according to feasibility and public health impact. While blood transfusion services using Ab-only RDTs for HIV screening should adopt higher sensitivity tests, surveillance and further research are needed to determine the need for novel HIV testing algorithms for those already using NAT and Ag/Ab screening assays.

Introduction

Highly accurate assays are currently available for HIV diagnosis, detecting nucleic acids, antigens, or HIV-specific antibodies (Abs). Typically, RNA becomes detectable in 10–14 days, p24 antigen (Ag) in 17–21 days, and Abs in 22–26 days following HIV acquisition [1,2]. However, currently available tests may undergo delays or fail to detect infections in a few circumstances. Exposure to antiretrovirals at or early after HIV acquisition can suppress viral replication, leading to diminished detectability of HIV RNA and p24, and an inconsistent antibody (Ab) response [3–7]. Currently available tests may therefore fail to detect infections in persons receiving early antiretroviral treatment (ART) [3,8,9]. Diagnosis delays may occur in the context of breakthrough infections in pre-exposure prophylaxis (PrEP) users, resulting in deferred treatment initiation and in the development of viral resistance when exposure to non-suppressive antiretroviral levels is maintained [10].

Further implications involve blood transfusion services. Blood banks can limit the risk of transfusion-transmitted HIV to nearly zero with the combination of donor health questionnaires and screening tests detecting HIV RNA, p24 Ag, and HIV-specific Abs [11]. Limitations in HIV detectability in persons with prior exposure to antiretrovirals are reflected in a recent publication by the US Food and Drug Administration, recommending a three-month deferral from the last dose of oral PrEP, and a two-year deferral from the last dose of injectable PrEP for candidate blood donors [12]. Accordingly, blood banks have also implemented questions addressing prior exposure to therapeutic or preventive antiretrovirals in the donation interview. Nevertheless, donors with evidence of recent exposure to medications used as PrEP or ART continue to present themselves for blood donation [13–16], highlighting the importance of understanding the magnitude of diagnostic limitations in this context.

Here, we used panels of archived plasma samples from PrEP trials and early ART initiation studies and the most sensitive currently licensed blood donor screening RNA and Ag/Ab combo (4th generation) assays to characterize the altered dynamics of viremia and seroconversion in the context of exposure to antiretrovirals at or early after HIV acquisition.

Methods

PrEP trials and samples selected for the study

iPrEx [17] and Partners PrEP [18] were randomized trials addressing the efficacy of PrEP compared to placebo for HIV prevention in vulnerable populations. iPrEx assigned 2,499 participants in a 1:1 ratio to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) or placebo, with enrollment between July/2007-December/2009. Partners PrEP assigned 4,747 participants in a 1:1:1 ratio to TDF/FTC, TDF, or placebo, with enrollment between July/2008-November/2010. Both trials assessed HIV status at enrollment and follow-up visits using point-of-care Ab-only rapid diagnostic tests (RDTs; 3^rd generation assays; description in supplementary materials), considered state-of-the-art for HIV diagnosis at the time. We obtained samples from visits prior to the first positive RDT, categorized into time intervals (≤8 weeks; 8–12 weeks; 12–16 weeks; and 16–52 weeks) relative to the first positive RDT. When more than one sample was available for the same interval, only the one collected closest to the first positive RDT was analyzed.

Early ART initiation studies and samples selected for the study

RV254/SEARCH 010 [19], henceforth referred to as RV254, identified individuals with recent HIV acquisition in a testing and counseling site in Bangkok between June/2009-February/2014. Participants underwent screening with an Ag/Ab assay, with further screening of reactive samples by a less sensitive Ab-only assay. Samples nonreactive by the Ag/Ab assay were screened using a nucleic acid test (NAT). Acute infection was defined for participants with reactive results in the Ag/Ab assay and nonreactive results in the less sensitive Ab-only assay, or for those with nonreactive results in the Ag/Ab assay and reactive results in the NAT. Participants with acute infection were categorized according to Fiebig stage [1] and offered immediate ART. In our analysis, we grouped participants initiating ART at Fiebig stages 1 or 2 (prior to Ab detection), and those initiating ART at Fiebig stages 3 or 4 (initial days following seroconversion). We obtained samples from the date of ART initiation (visit 1), and from visits conducted 12 and 24 weeks afterwards (visits 2 and 3).

The SeroIncidence Panel Project (SIPP) identified patients with recent HIV acquisition in a sexually transmitted infections clinic in San Francisco between December/2008-August/2013, with early ART initiation and serial sample collections. We obtained samples from participants starting ART up to two months after the first positive test. We estimated the Fiebig stage at ART initiation for SIPP participants using Fiebig stage at diagnosis, time between diagnosis and ART initiation, and expected duration of each stage [1].

Laboratory assays

Plasma samples were tested for HIV RNA using the Roche cobas MPX NAT assay, which qualitatively detects HIV-1 Groups M and O RNA, and HIV-2 RNA (https://www.fda.gov/vaccines-blood-biologics/cobas-mpx). Samples were also tested with three Ag/Ab assays designed for qualitative detection of Abs to HIV-1, including groups M and O, anti-HIV-2, and p24 Ag: Abbott Alinity s HIV Ag/Ab Combo (https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/alinity-s-hiv-agab-combo-assay); Roche Elecsys HIV Duo (https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/elecsys-hiv-duo); and Ortho VITROS HIV Combo (https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/vitros-immunodiagnostic-products-hiv-combo-reagent-pack-vitros-immunodiagnostic-products-hiv-combo). Tests were performed according to the manufacturers’ instructions, with the exception that samples were stored at ≤−20°C beyond labeled claims.

Statistical analysis

We compared participants assigned to active PrEP or placebo, and participants initiating ART at Fiebig stages 1/2 or 3/4 in RV254, using chi-square or Fisherś exact tests. Comparisons of signal-to-cutoff (SCO), cutoff index (COI), and cycle threshold (CT) values were done using Wilcoxon Rank-Sum tests; SCO/COI were also compared using repeated measures models with spline fixed effects for days prior to detection by RDT, and random effects for subjects. For the Roche Elecsys Ag/Ab assay, which provides separate values for Ag, Ab, and overall COI, our analysis considered the overall COI. Results obtained from SIPP samples were presented graphically, with no statistical analysis due to small sample size. We used Stata 17.0 (StataCorp College Station, TX: StataCorp LP) and SAS (SAS Institute Inc. 2023, NC:SAS Institute Inc.) for all analyses.

Ethical aspects

The studies providing samples for this analysis received approval from relevant ethics committees and obtained formal consent from participants, including consent for further testing of repository samples. Vitalant Research Institute’s institutional review board (IRB) of record, the University of California San Francisco IRB, approved this study (approval number 19–28950) as non-human subjects research with exemption of additional informed consent, since samples were coded and anonymized before shipment to testing facilities.

Results

Study population and characteristics

We obtained samples from 251 participants with HIV infection identified during iPrEx or Partners PrEP; of those, 150 were assigned to placebo, and 101 to active PrEP (Figure 1a). In the active PrEP arm, 65 (64%) had been assigned to TDF/FTC and 36 (26%) to TDF. From RV254 we obtained samples from 55 participants, of whom 25 initiated ART at Fiebig stages 1/2, and 30 initiated ART at Fiebig stages 3/4. Visit 2 samples were collected at a median of 83 days after ART initiation and visit 3 samples were collected at a median of 168 days after ART initiation (Figure 1b). Finally, we obtained samples from 17 SIPP participants; two started ART at estimated Fiebig stage 4, and 15 started ART at estimated Fiebig stage 5. SIPP participants were followed for a median of 10 visits (range 3–16), with a median follow-up time of 394 days (range 40–692; Figure 1b). Basic demographic characteristics of study participants are described in the supplementary materials.

Figure 1.

Participants and samples included in the study. (a) Participants and samples from PrEP trials. (b) Participants and samples from early antiretroviral initiation studies.

Evidence of HIV infection before detection by RDT in PrEP trials

The percentages of samples from PrEP trials with reactive results before detection by RDT is shown in Figure 2a. Reactivity using NAT and Ag/Ab assays in samples collected up to 8 weeks prior to the first reactive RDT varied between 49–61% for active PrEP users and between 27–37% for placebo users. Positive tests were progressively less frequent at earlier timepoints, with consistently higher percentages for participants assigned to active PrEP compared to placebo, achieving statistical significance in the ≤8 weeks timepoint for all assays. Combining NAT and Ag/Ab tests further increased positivity (Figure 2b), although not reaching statistical significance when compared to Ag/Ab tests alone. We next explored whether the Ab signals and NAT CT values differed between placebo and PrEP arms. Ag/Ab levels were significantly higher, and reactivity was identified earlier in participants assigned to active PrEP, suggesting that HIV infection could have been detected earlier than among those in placebo arms had higher sensitivity assays been used (Figure 3). In contrast, we found no significant differences in NAT CT values comparing active PrEP and placebo groups; moreover, PrEP and placebo groups had similar SCO/COI values in the strata of reactives and nonreactives (Supplementary Figure 1).

Figure 2.

Evidence of infection prior to detection by rapid tests, according to PrEP treatment assignment. (a) Percentages and 95% confidence intervals of positive results at each time interval prior to the date of the first positive rapid test according to treatment assignment. (b) Percentages and 95% confidence intervals with evidence of infection using antigen/antibody detection tests alone or in combination in samples collected up to 8 weeks prior to detection by rapid tests, according to PrEP treatment assignment. The combination of NAT and antigen/antibody tests increased positivity, although not reaching statistical significance when compared to antigen/antibody tests alone.

Figure 3.

Antibody signals and corresponding smoothed splines in samples collected prior to detection by rapid test in PrEP trials. P-values calculated using repeated measures spline regressions comparing placebo and active PrEP groups.

HIV detectability after early ART initiation

At ART initiation (visit 1), all RV254 participants had reactive NAT (by definition of study eligibility), with lower percentages in subsequent visits, as expected for HIV suppression following ART (Figure 4). Reactivity in Ag/Ab tests was below 100% for all three Ag/Ab tests across all visits, with consistently lower positivity among participants initiating ART at Fiebig stages 1/2 compared to those initiating ART at Fiebig stages 3/4, and some variability across assays.

Figure 4.

Test positivity at and following early ART initiation in RV254. Percentages and 95% confidence intervals of positive test results in RV254 participants, overall and by Fiebig stage at ART initiation. Tests performed in all samples (N=55) with up to one missing observation per visit.

Episodes of seroreversion, defined here as a nonreactive test in a sample collected from a participant with a previously reactive result on the same assay, were identified in 16 of 55 RV254 participants (29%, 95% CI 18–43%), predominantly between visits 1 and 2 (15 of 16); seroreversions were non-significantly more frequent among those initiating ART at Fiebig stages 1/2 (36%; 95% CI 18–57%) than those initiating ART at Fiebig stages 3/4 (23%; 95% CI 10–42%). Supplementary Figure 2 shows test trajectories for each of the 16 participants with seroreversion at any timepoint.

To investigate the ability of blood donation screening tests to detect HIV infection in RV254 participants, we identified samples with concordant nonreactive results in Ag/Ab and NAT assays (Table 1). At visit 1, HIV status would be identified for all participants; most (67%) had positive results in all Ag/Ab tests and in NAT. However, at visit 2, 7 samples had nonreactive results in all Ag/Ab tests and undetectable NAT, and an additional 13 samples had nonreactive results in at least one Ag/Ab test and undetectable NAT; in total, blood donation screening could have missed up to 20 out of 55 RV254 participants (36%) at visit 2. At visit 3, 6 samples had nonreactive results in all Ag/Ab tests and undetectable NAT, and an additional 8 samples had nonreactive results in at least one Ag/Ab test and undetectable NAT; in total, blood donation screening could have missed up to 14 out of 55 RV254 participants (25%) at visit 3. Of note, 5 of the 6 participants with nonreactive results in all Ag/Ab tests and undetectable NAT at visit 3 started ART at Fiebig 1, and all six had identical results at visit 2. One participant with nonreactive results in all Ag/Ab tests and undetectable NAT at visit 2 became NAT-positive at visit 3, but with a very low viral load (CT=39.55), which would possibly be missed by pooled NAT widely used in blood bank screening.

Table 1.

Tests pattern and RV254 samples possibly missed by blood donation screening tests.

Tests pattern
Roche cobas MPX	+	+	+	+	+	+	+	−	+	NT	−	−	−
Abbott Alinity	+	NT	−	+	+	−	−	+	NT	+	−	−	−
Roche Elecsys	+	+	+	−	−	−	−	+	−	+	+	−	−
Ortho VITROS	+	+	+	+	−	+	−	+	NT	+	+	+	−
Results - N
Visit 1- ART initiation	37	0	1	2	1	2	10	0	1	1	0	0	0
Visit 2 –12 weeks	22	1	4	0	0	0	0	7	0	1	8	5	7
Visit 3– 24 weeks	19	0	3	0	0	2	1	16	0	0	7	1	6

ART, antiretroviral treatment, NT, not tested.

Gray cells denote samples potentially missed by blood donation screening, depending on antigen/antibody test. Light red cells denote samples that would be missed by blood donation screening, regardless of antigen/antibody test.

Samples from SIPP participants, who started ART during Fiebig stages 4 or 5, were reactive for all Ag/Ab tests at all timepoints after ART initiation. Supplementary Figure 3 shows test trajectories. We observed rising SCO/COI levels along the initial timepoints, corresponding to recent infection phases, and no evidence of SCO/COI levels waning over time.

Discussion

In this study, we found that positive NAT or Ag/Ab assays while Ab-only RDTs were still negative were consistently more frequent for participants in PrEP trials assigned to active PrEP compared to those assigned to placebo, suggesting that exposure to PrEP increases the likelihood of falsely negative results in Ab-only RDTs. Moreover, Ag/Ab positivity was identified longer before Ab-only RDT seroconversion in participants assigned to active PrEP than in those assigned to placebo, suggesting longer duration of undetected infection. Among RV254 participants, who started ART very early following infection, the reactivity in Ag/Ab assays was below 100% at all timepoints, and lower among those initiating ART at Fiebig stages 1/2 compared to those initiating ART at Fiebig stages 3/4. Seroreversions were observed in 16 of 55 RV254 participants between ART initiation and visit 3; moreover, blood donation screening tests could have missed up to 20 cases (36%) at visit 2 and up to 14 cases (25%) at visit 3. In contrast, among SIPP participants, who started ART at later timepoints, Ag/Ab assays were able to identify infections with no evidence of SCO/COI waning over time. These results indicate reduced HIV detectability by Ag/Ab assays due to very early ART initiation. Similar diagnostic limitations could be anticipated in PrEP breakthrough infections [7,20,21], with implications for individual diagnostics and for HIV screening in blood banks.

Our findings are consistent with previous studies addressing the effect of antiretroviral exposure at or early after HIV acquisition on viral replication and Ab responses. PrEP use has been associated with slower and hindered Ab maturation [22], elongated time to Fiebig stages, and delayed detection of infection [5]. In the HPTN 067/ADAPT trial, HIV infection was detectable using laboratory-based Ag/Ab assays and/or NAT while both the Ab-only RDTs used in the study were nonreactive in 9 of 12 participants; one participant was retrospectively identified with acute infection at randomization, remaining undiagnosed and on PrEP for 3–4 months with repeatedly nonreactive RDT, low HIV viral load, and low SCO in Ag/Ab assays. This study found resistance mutations in 3 of 12 participants with HIV infection detected during the trial [6]. Other reports describing PrEP users with breakthrough HIV infection have shown very low and inconsistent reactivity in both NAT and serologic assays [20,21].

Delays in infection detection among PrEP users were also reported in more recent studies addressing the efficacy of injectable cabotegravir compared to oral TDF/FTC, which adopted parallel testing with Ab-only RDT and laboratory-based Ag/Ab assays. Delays varied between 4–26 weeks in the cabotegravir arm, and between 1–12 weeks in the TDF/FTC arm. In HPTN 083, testing at study sites failed to detect infections on at least one study visit in 21 of 58 cases (36%) in the cabotegravir arm and 10 of 42 cases (24%) in the TDF/FTC arm [7]. HPTN 084 reported delayed site detection of HIV infection in nine participants, in some cases leading to emergence of drug resistance [10]. Importantly, four participants receiving cabotegravir near the time of infection in HPTN 083 had seroreversion [7]. The longer half-life of cabotegravir compared to oral PrEP medications probably explains the higher risk of both delayed diagnosis and emergence of resistance mutations.

These findings motivated new recommendations in the 2021 Centers for Disease Control and Preventionś guidelines for PrEP, which suggest the adoption of both laboratory-based Ag/Ab and NAT testing for people who are taking or have recently taken PrEP or HIV post-exposure prophylaxis (PEP) [23]. The new testing algorithm is recommended for people exposed to oral PrEP/PEP in the past 3 months and people exposed to injectable cabotegravir in the past 12 months. Although our findings also indicate that adopting higher sensitivity tests in PrEP programs could enhance HIV detection, implications of expanded testing algorithms should be considered relative to benefits and risks, resource needs, and feasibility of such an approach from a public health perspective. Current guidance from the Word Health Organization (WHO) supports differentiation and simplification of service delivery models to expand access to PrEP, including recommendations for the adoption of HIV self-testing with RDT [24]. The implementation of tests with higher cost, complexity, and turnaround time could hinder the expansion of PrEP programs and restrict the number of potential users, particularly in resource-limited settings. Finally, considerations and risks might be different for oral versus long acting injectable PrEP modalities [25]. Studies investigating the cost-effectiveness of different testing algorithms for PrEP users should be conducted to assess the best recommendations in different settings.

Our results are also aligned with previous studies demonstrating that persons with HIV (PWH) with ART initiation at acute or early stages may either fail to seroconvert and/or have seroreversion over time. Hare et al. [8], identified decreasing Ab reactivity over time and six cases of seroreversion in 2nd generation assays among 87 individuals initiating ART during acute or early HIV stages. Stefic et al. [26] evaluated serological responses in 44 participants with early ART initiation; although Ag/Ab assays remained reactive, 16% had low reactivity, and 13 participants tested negative with an Ab-only RDT. A study assessing 70 individuals initiating ART at acute or early infection showed no signs of declining signal intensity using Ag/Ab assays over three years; however, positivity in Ab-only or Ag/Ab RDTs ranged between 50–83% among participants with very early treatment [3]. Samples from RV254 had been analyzed in two previous studies; De Souza et al. [27], reported 17% nonreactivity and 11% seroreversion among 234 participants following 24 weeks of ART using Ag/Ab assays. Manak et al. [9], analyzed the performance of three Ag/Ab assays using samples from 84 RV254 participants; at 24 weeks, nonreactive results occurred for 52% of those initiating ART at Fiebig 1, and seroreversion was observed for 13 individuals. Together with our findings, these studies show that laboratory-based Ag/Ab assays are more sensitive than RDTs in detecting infections among PWH with early ART initiation; however, with very early treatment, even these higher sensitivity assays may fail to detect HIV infections. We found that seroreversions occurred in RV254 participants, but not in those from SIPP, for whom ART was initiated later. Moreover, we saw no evidence of waning SCO/COI levels over a median of 394 days after ART initiation in SIPP participants. HIV clade differences between RV254 and SIPP infections are unlikely to justify this divergency since the Ag/Ab tests adequately detect relevant clades expected in both study locations. These findings suggest that diagnostic limitations using laboratory-based Ag/Ab assays are unlikely to occur among PWH initiating ART at or after Fiebig 5.

Our study brings important and timely information for blood transfusion services. Screening algorithms adopted in many countries include parallel testing using laboratory-based Ag/Ab and NAT assays, which essentially eliminated the risk of HIV transfusion-transmission [11]. However, in a survey conducted by the WHO, only 29 of 171 countries (17%) reported having a policy for screening all blood donations with a combination of NAT, p24 Ag, and HIV-specific Abs [28], and many blood collection organizations in resource-limited countries, particularly in Africa, still rely exclusively on RDTs for HIV screening [29,30]. In the context of expanding PrEP use and increasing prevalence of PWH with early ART initiation, potential limitations in the sensitivity of screening assays bring concerns to the safety of blood supplies, particularly but not exclusively for blood banks that don’t use parallel Ag/Ab and NAT testing in the donation screening [31]. Moreover, with recent modifications in donor deferral policies in the US [12] and in other countries, the proportion of potential donors with exposure to antiretrovirals, which was very low in recent studies, [13–16] may increase. Since donors with undisclosed HIV infection under ART will likely have negative HIV NAT results, laboratory screening of donation samples is limited to infection detectability by Ag/Ab tests. While the “zero risk” status of a PWH with undetectable HIV viral load is grounded on robust evidence for sexual transmission [32], a much larger volume of potentially infectious fluid is transferred with blood transfusions, which also circumvents the mucosal barrier. Of note, no HIV transfusion-transmission has been documented since changes in donor deferral criteria were implemented. Our results reinforce that screening with parallel laboratory-based Ag/Ab and NAT assays should be ensured in blood transfusion services. Continuous surveillance and further research are needed to understand the infectivity of plasma NAT-negative and Ag/Ab-nonreactive donations, as well as to evaluate, in different settings: 1. the frequency of donations from persons with undisclosed exposure to PrEP/PEP; 2. the risk of undiagnosed breakthrough HIV infection in PrEP users who donate blood; and 3. the frequency of ART initiation during acute infection stages among blood donors with undisclosed HIV infection. Existing data suggests that these are very rare events. Understanding the magnitude of risks will help determine the need for novel screening algorithms, including modifications in the donor health questionnaire, more sensitive Ag/Ab and NAT tests (potentially enhanced by testing whole blood rather than plasma [33]), or even the testing for antiretrovirals in donation samples.

Limitations of this study should be mentioned. Our findings are not generalizable to settings using less sensitive commercially available NAT and serologic tests. We analyzed samples collected several years ago, with storage time surpassing the manufacturers’ labeled claims for diagnostic. However, this limitation occurred equally for antiretroviral-exposed and -unexposed samples in PrEP studies, possibly biasing our findings towards the null hypothesis. Low volumes precluded testing of all samples in all Ag/Ab platforms, limiting comparisons across manufacturers. Furthermore, tests were conducted at different laboratories, and inaccuracies due to laboratory errors, including multiple freeze-thaw cycles and sample switch, cannot be ruled out. We revised our dataset to identify potentially conflicting results and found no substantial differences in our findings in a sensitivity analysis excluding participants with inconsistent longitudinal values. We had limited information regarding adherence to PrEP and ART from the original studies. Finally, we included samples from study participants, who may not represent the overall population of people exposed to antiretrovirals undergoing HIV testing in routine clinical or blood screening settings.

Despite these limitations, our study provides further evidence that exposure to antiretrovirals early after HIV acquisition may reduce the ability of NAT and Ag/Ab tests to detect HIV infection. We also observed diagnostic limitations of Ab-only RDTs in persons exposed to PrEP. Our findings suggest that blood transfusion services relying exclusively on Ab-only RDTs for HIV screening should adopt higher sensitivity tests. Considerations for the implementation of NAT and Ag/Ab tests in PrEP/PEP programs should be balanced according to the feasibility and impact of such an approach from a public health perspective. Our results reinforce that the currently negligible estimates of residual risk of HIV transmission through blood transfusion may be altered in the context of expanding PrEP use and increasing prevalence of PWH with early ART initiation.

Data availability statement

Currently, the datasets used and/or analyzed during the study are available from the authors on reasonable request.