Dataset Information

Brief Report: Quantifiable Plasma Tenofovir Among South African Women Using Daily Oral Pre-exposure Prophylaxis During the ECHO Trial.

ABSTRACT:

Background

HIV endpoint-driven clinical trials provide oral pre-exposure prophylaxis (PrEP) as HIV prevention standard of care. We evaluated quantifiable plasma tenofovir among South African women who used oral PrEP during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.

Methods

ECHO, a randomized trial conducted in 4 African countries between 2015 and 2018, assessed HIV incidence among HIV-uninfected women, aged 16-35 years, randomized to 1 of 3 contraceptives. Oral PrEP was offered onsite as part of the HIV prevention package at the South African trial sites. We measured tenofovir in plasma samples collected at the final trial visit among women reporting ongoing PrEP use. We used bivariate and multivariate logistical regression to assess demographic and sexual risk factors associated with plasma tenofovir quantification.

Results

Of 260 women included, 52% were ≤24 years and 22% had Chlamydia trachomatis at enrollment. At PrEP initiation, 68% reported inconsistent/nonuse of condoms. The median duration of PrEP use was 90 days (IQR: 83-104). Tenofovir was quantified in 36% (n = 94) of samples. Women >24 years had twice the odds of having tenofovir quantified vs younger women (OR = 2.12; 95% confidence interval = 1.27 to 3.56). Women who reported inconsistent/nonuse of condoms had lower odds of tenofovir quantification (age-adjusted OR = 0.47; 95% confidence interval = 0.26 to 0.83).

Conclusions

Over a third of women initiating PrEP and reporting ongoing use at the final trial visit had evidence of recent drug exposure. Clinical trials may serve as an entry point for PrEP initiation among women at substantial risk for HIV infection with referral to local facilities for ongoing access at trial end.

Clinical trial number

NCT02550067.

SUBMITTER: Beesham I

PROVIDER: S-EPMC9377486 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Brief Report: Quantifiable Plasma Tenofovir Among South African Women Using Daily Oral Pre-exposure Prophylaxis During the ECHO Trial.

Beesham Ivana I Mansoor Leila E LE Joseph Davey Dvora L DL Palanee-Phillips Thesla T Smit Jenni J Ahmed Khatija K Selepe Pearl P Louw Cheryl C Singata-Madliki Mandisa M Kotze Philip P Heffron Renee R Parikh Urvi M UM Wiesner Lubbe L Rees Helen H Baeten Jared M JM Beksinska Mags M

Journal of acquired immune deficiency syndromes (1999) 20220609 1

<h4>Background</h4>HIV endpoint-driven clinical trials provide oral pre-exposure prophylaxis (PrEP) as HIV prevention standard of care. We evaluated quantifiable plasma tenofovir among South African women who used oral PrEP during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.<h4>Methods</h4>ECHO, a randomized trial conducted in 4 African countries between 2015 and 2018, assessed HIV incidence among HIV-uninfected women, aged 16-35 years, randomized to 1 of 3 contraceptive ...[more]

PMID: 35972853

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Project description:Globally HIV remains a major public health problem. In sub-Saharan Africa most new HIV infections occur in adolescent girls and young women. Previously tested antiretroviral drugs as different pre-exposure prophylaxis (PrEP) formulations have shown inconsistent levels of protection against HIV in African women. Besides adherence, biological factors such as drug transporter proteins are increasingly recognized as key modulators of PrEP levels. Drug transporter mRNA expression levels has been significantly correlated to altered PrEP levels in-vitro in different tissues, with inflammation identified as a further modifier of drug transporters mRNA expression and thus PrEP levels. We therefore, aimed to determine possible concordance between drug transporter mRNA expression in the female genital tract (FGT) and blood of N = 45 South African women taking oral PrEP-Truvada® [TDF/FTC)] over 6 months for HIV prevention. Additionally, we determined associations between drug transporter mRNA expression, genital inflammation, and blood-tenofovir diphosphate (TFV-DP). mRNA-expression of four efflux P-gp; MATE-1; MRP-2; MRP-4 and two influx OAT-1 and OAT-3 drug transporters were determined by qRT-PCR. Multiplexed technology was used to measure 27 cytokines to define genital inflammation. Significant positive correlations of mRNA expression for P-gp, MATE-1, MRP-2, and MRP-4 were observed between the FGT and blood at 3- and 6-months post-PrEP initiation (p < 0.05). For OAT-1 however, significant positive correlations were observed pre- and post-PrEP exposure (p < 0.05). Linear-mixed models showed moderate associations between FGT cytokines and drug transporter mRNA expression, with a direct relationship observed between MIP-1β concentration and MATE-1 mRNA expression. Similarly, PLS-DA showed that in women with genital inflammation, consistently higher mRNA expression of MATE-1 was observed compared to women without genital inflammation. No significant associations were observed between drug transporter mRNA expression and blood TFV-DP. Our results suggest that drug transporters may be similarly expressed in the FGT and blood. Furthermore, genital inflammation may modify PrEP levels by altering drug transporter mRNA expression. Collectively, our data may be used to better understand biological factors that may affect PrEP efficacy in African women who remain vulnerable to HIV.

Project description:BackgroundHIV incidence among adolescents in southern Africa remains unacceptably high. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention but there are few data on its implementation among adolescents. We aimed to investigate the safety, feasibility, and acceptability of PrEP with oral tenofovir disoproxil fumarate and emtricitabine as part of a comprehensive HIV prevention package in an adolescent population in South Africa.MethodsThis open-label single-arm phase 2 study (PlusPills) was done in two research clinics in Cape Town and Johannesburg, South Africa. Adolescents aged 15-19 years were recruited into the study through recruitment events and outreach in the community. Potential participants were eligible for enrolment if they reported being sexually active. Exclusion criteria were a positive test for HIV or pregnancy at enrolment, breastfeeding, or any relevant co-morbidities. Participants were given oral tenofovir disoproxil fumarate and emtricitabine for PrEP to take daily for the first 12 weeks and were then given the choice to opt in or out of PrEP use at three monthly intervals during scheduled clinic visits. Participants were invited to monthly visits for adherence counselling and HIV testing during the study period. The primary outcomes were acceptability, use, and safety of PrEP. Acceptability was measured by the proportion of participants who reported willingness to take up PrEP and remain on PrEP at each study timepoint. Use was defined as the number of participants who continued to use PrEP after the initial 12-week period until the end of the study (week 48). Safety was measured by grade 2, 3, and 4 laboratory and clinical adverse events using the Division of AIDS table for grading the severity of adult and paediatric adverse events, version 1.0. Dried blood spot samples were collected at each study time-point to measure tenofovir diphosphate concentrations. This trial is registered with ClinicalTrials.gov, NCT02213328.FindingsBetween April 28, 2015, and Nov 11, 2016, 244 participants were screened, and 148 participants were enrolled (median age was 18 years; 99 participants [67%] were female) and initiated PrEP. PrEP was stopped by 26 of the 148 (18%) participants at 12 weeks. Cumulative PrEP opt-out, from the total cohort, was 41% (60 of 148 participants) at week 24 and 43% (63 of 148 participants) at week 36. PrEP was well tolerated with only minor adverse events (grade 2) thought to be related to study drug, which included headache (n=4, 3%), gastrointestinal upset (n=8, 5%), and skin rash (n=2, 1%). Two participants (1%) experienced grade 3 weight loss, which was deemed related to the study drug and resolved fully when PrEP was discontinued. Tenofovir diphosphate concentrations were detectable (>16 fmol/punch) in dried blood spot samples in 108 (92%) of 118 participants who reported PrEP use at week 12, in 74 (74%) of 100 participants at week 24, and in 22 (59%) of 37 participants by the study end at week 48.InterpretationIn this cohort of self-selected South African adolescents at risk of HIV acquisition, PrEP appears safe and tolerable in those who continued use. PrEP use decreased throughout the course of the study as the number of planned study visits declined. Adolescents in southern Africa needs access to PrEP with tailored adherence support and possibly the option for more frequent and flexible visit schedules.FundingNational Institute of Allergy and Infectious Diseases of the US National Institutes of Health.

Dataset Information

Brief Report: Quantifiable Plasma Tenofovir Among South African Women Using Daily Oral Pre-exposure Prophylaxis During the ECHO Trial.

Background

Methods

Results

Conclusions

Clinical trial number

Publications

Brief Report: Quantifiable Plasma Tenofovir Among South African Women Using Daily Oral Pre-exposure Prophylaxis During the ECHO Trial.

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