PrEP uptake, persistence, adherence, and effect of retrospective drug level feedback on PrEP adherence among young women in southern Africa: Results from HPTN 082, a randomized controlled trial

Background Pre-exposure prophylaxis (PrEP) is highly effective and an important prevention tool for African adolescent girls and young women (AGYW), but adherence and persistence are challenging. PrEP adherence support strategies for African AGYW were studied in an implementation study. Methods and findings HIV Prevention Trials Network (HPTN) 082 was conducted in Cape Town, Johannesburg (South Africa) and Harare (Zimbabwe) from October 2016 to October 2018 to evaluate PrEP uptake, persistence, and the effect of drug level feedback on adherence. Sexually active HIV–negative women ages 16–25 were offered PrEP and followed for 12 months; women who accepted were randomized to standard adherence support (counseling, 2-way SMS, and adherence clubs) or enhanced adherence support with adherence feedback from intracellular tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). PrEP uptake, persistence through 12 months (no PrEP hold or missed visits), and adherence were assessed. The primary outcome was high adherence (TFV-DP ≥700 fmol/punch) at 6 months, compared by study arm. Of 451 women enrolled, median age was 21 years, and 39% had curable sexually transmitted infections (STIs). Most (95%) started PrEP, of whom 55% had uninterrupted PrEP refills through 12 months. Of those with DBS, 84% had detectable TFV-DP levels at month 3, 57% at month 6, and 31% at month 12. At 6 months, 36/179 (21%) of AGYW in the enhanced arm had high adherence and 40/184 (22%) in the standard adherence support arm (adjusted odds ratio [OR] of 0.92; 95% confidence interval [CI] 0.55, 1.34; p = 0.76). Four women acquired HIV (incidence 1.0/100 person-years), with low or undetectable TFV-DP levels at or prior to seroconversion, and none of whom had tenofovir or emtricitabine resistance mutations. The study had limited power to detect a modest effect of incentives on adherence, and there was limited awareness of PrEP at the time the study was conducted. Conclusions In this study, PrEP initiation was high, over half of study participants persisted with PrEP through month 12, and the majority of young African women had detectable TFV-DP levels through month 6 with one-fifth having high adherence. Drug level feedback in the first 3 months of PrEP use did not increase the proportion with high adherence at month 6. HIV incidence was 1% in this cohort with 39% prevalence of curable STIs and moderate PrEP adherence. Strategies to support PrEP use and less adherence-dependent formulations are needed for this population. Trial registration ClinicalTrials.gov NCT02732730.

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The effect of a conditional cash transfer on HIV incidence in young women in rural South Africa (HPTN 068): a phase 3, randomised controlled trial

The Lancet Global Health ◽

10.1016/s2214-109x(16)30253-4 ◽

2016 ◽

Vol 4 (12) ◽

pp. e978-e988 ◽

Cited By ~ 111

Author(s):

Audrey Pettifor ◽

Catherine MacPhail ◽

James P Hughes ◽

Amanda Selin ◽

Jing Wang ◽

...

Keyword(s):

South Africa ◽

Young Women ◽

Controlled Trial ◽

Conditional Cash Transfer ◽

Cash Transfer ◽

Hiv Incidence ◽

Phase 3 ◽

Rural South ◽

Randomised Controlled ◽

Rural South Africa

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1298. Acquisition of TDF-Susceptible HIV Despite High Level Adherence to Daily TDF/FTC PrEP as Measured by Dried Blood Spot (DBS) and Segmental Hair Analysis: A Case Report

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1131 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S396-S397 ◽

Cited By ~ 1

Author(s):

Stephanie E Cohen ◽

Darpun Sachdev ◽

Sulggi Lee ◽

Susan Scheer ◽

Oliver Bacon ◽

...

Keyword(s):

Hiv Infection ◽

Genetic Distance ◽

Dried Blood Spots ◽

Resistance Mutations ◽

Research Support ◽

Hiv Surveillance ◽

Hiv Rna ◽

Art Initiation ◽

High Adherence ◽

Research Grant

Abstract Background Pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir (TFV) disoproxil fumarate (FTC/TDF) is highly protective against HIV infection. We report the second case of acquisition of TDF-susceptible HIV despite high adherence to PrEP, confirmed by drug level testing. Methods PrEP adherence was assessed by measuring FTC/TDF metabolites in dried blood spots (DBS) and FTC/TFV concentrations in segments of scalp hair. Genotypic and phenotypic resistance were evaluated. HIV partner services (PS) and HIV sequences reported to HIV surveillance with a genetic distance ≤1.5% (by HIV-Trace) identified likely transmission partners. Results A 21-year-old Latino man presented 13 months after PrEP initiation. He was HIV negative by rapid HIV antibody (Ab) and HIV RNA pooling (detection limit ~40 copies/mL) at PrEP initiation and at months 3, 6, and 10. At the 13-month visit, he was asymptomatic and his rapid HIV Ab was negative. Five days later, his HIV RNA was reported as positive (559 copies/mL). He was notified of the result, linked to care and immediately started antiretroviral treatment (ART), at which point his RNA was 1544 copies/mL and his HIV Ab test was positive. The HIV genotype had M184V, L74V and K103N mutations and phenotypic susceptibility to TDF. TFV/FTC levels by LC-MS/MS measured in 1 cm segments of hair collected at ART initiation indicated consistently high PrEP adherence in each of the preceding 6 months. TFV-diphosphate and FTC-triphosphate levels in DBS collected 2 days after ART initiation were 1012 fmol/punch and 0.266 pmol/punch, confirming high adherence over the preceding 6 weeks. Between PrEP initiation and HIV acquisition, he had 1 episode of urethral chlamydia and three episodes of urethral gonorrhea. The likely transmission partner, named during PS, had no history of viral suppression in HIV surveillance and harbored the same resistance mutations, with a genetic distance between the two patients of 0.66%. The partner was re-linked to care and had a current HIV RNA of 15,130 copies/mL. Conclusion Acquisition of TDF-susceptible HIV infection can occur despite high PrEP adherence. Quarterly HIV and STD screening of patients on PrEP, combined with prompt linkage to care and PS for those diagnosed with HIV, facilitates early diagnosis and prevents further transmission of HIV. Disclosures S. E. Cohen, Gilead: Investigator in PrEP study for which Gilead donated drug, donated study drug and paid for drug testing during the PrEP demo project, of which I was a co-PI (the study has ended). S. Lee, Viiv Healthcare: Investigator, Research grant. Gilead Sciences: Investigator, Research grant. P. Anderson, Gilead: Consultant and Investigator, funds were paid to the institution for contract work and grant support and Research support. D. Havlir, Gilead: Investigator, Gilead Sciences provides antiretroviral therapy for a NIH funded study that she is conducting and Research support.

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Improving Uptake and Adherence to HIV Prevention Services With Pre-exposure Prophylaxis (PrEP), HIV Self- Testing and Adherence Support for Very High Risk HIV-negative Young Women Aged 15-24 in Kampala, Uganda

Case Medical Research ◽

10.31525/ct1-nct04030520 ◽

2019 ◽

Author(s):

Keyword(s):

High Risk ◽

Hiv Prevention ◽

Young Women ◽

Prevention Services ◽

Self Testing ◽

Adherence Support ◽

Exposure Prophylaxis ◽

Very High ◽

Hiv Negative

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Faculty Opinions recommendation of Impact of acyclovir on genital and plasma HIV-1 RNA, genital herpes simplex virus type 2 DNA, and ulcer healing among HIV-1-infected African women with herpes ulcers: a randomized placebo-controlled trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1162756.624352 ◽

2009 ◽

Author(s):

Anne Buvé

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Genital Herpes ◽

Herpes Simplex Virus Type ◽

Ulcer Healing ◽

Controlled Trial ◽

African Women ◽

Simplex Virus ◽

Hiv 1

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The Community PrEP Study: a randomized control trial leveraging community-based platforms to improve access and adherence to pre-exposure prophylaxis to prevent HIV among adolescent girls and young women in South Africa—study protocol

Trials ◽

10.1186/s13063-021-05402-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Andrew Medina-Marino ◽

Dana Bezuidenhout ◽

Sybil Hosek ◽

Ruanne V. Barnabas ◽

Millicent Atujuna ◽

...

Keyword(s):

South Africa ◽

Adolescent Girls ◽

Young Women ◽

Randomized Control Trial ◽

Community Based ◽

Adherence Support ◽

Randomized Control ◽

Exposure Prophylaxis ◽

Effective Use ◽

Improve Access

Abstract Background HIV incidence among South African adolescent girls and young women (AGYW) remains high, but could be reduced by highly effective pre-exposure prophylaxis (PrEP). Unfortunately, AGYW report significant barriers to clinic-based sexual and reproductive health services. Even when AGYW access PrEP as an HIV prevention method, poor prevention-effective use was a serious barrier to achieving its optimal HIV prevention benefits. Determining the acceptability and feasibility of community-based platforms to increase AGYW’s access to PrEP, and evaluating behavioural interventions to improve prevention-effective use of PrEP are needed. Methods We propose a mixed-methods study among AGYW aged 16–25 years in Eastern Cape Province, South Africa. In the first component, a cross-sectional study will assess the acceptability and feasibility of leveraging community-based HIV counselling and testing (CBCT) platforms to refer HIV-negative, at-risk AGYW to non-clinic-based, same-day PrEP initiation services. In the second component, we will enrol 480 AGYW initiating PrEP via our CBCT platforms into a three-armed (1:1:1) randomized control trial (RCT) that will evaluate the effectiveness of adherence support interventions to improve the prevention-effective use of PrEP. Adherence will be measured over 24 months via tenofovir-diphosphate blood concentration levels. Qualitative investigations will explore participant, staff, and community experiences associated with community-based PrEP services, adherence support activities, study implementation, and community awareness. Costs and scalability of service platforms and interventions will be evaluated. Discussion This will be the first study to assess the acceptability and feasibility of leveraging CBCT platforms to identify and refer at-risk AGYW to community-based, same-day PrEP initiation services. It will also provide quantitative and qualitative results to inform adherence support activities and services that promote the prevention-effective use of PrEP among AGYW. By applying principles of implementation science, behavioural science, and health economics research, we aim to inform strategies to improve access to and prevention-effective use of PrEP by AGYW. Trial registration ClinicalTrials.govNCT03977181. Registered on 6 June 2019—retrospectively registered.

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Improved adherence with Medicines Use Review service in Slovenia: a randomized controlled trial

BMC Health Services Research ◽

10.1186/s12913-021-06223-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Urška Nabergoj Makovec ◽

Igor Locatelli ◽

Mitja Kos

Keyword(s):

Medication Adherence ◽

Controlled Trial ◽

Test Group ◽

Multiple Linear Regression Model ◽

Relative Difference ◽

Control Group ◽

Adherence Support ◽

Medicines Use ◽

The Impact ◽

Medicines Use Review

Abstract Background Based on several existing patient-oriented activities, Medicines Use Review (MUR) service was standardized and officially adopted in Slovenia in 2015. Service aims to provide adherence support and ensure safe and effective medicines use. Therefore, the aim of the study was to evaluate the benefits of MUR in Slovenia, primarily the impact on medication adherence. Methods A randomised controlled trial was performed in community pharmacies to compare MUR with standard care. Patients were randomised into either the test (patients received MUR by a certified MUR provider at visit 1), or control group. The study primary outcome was self-reported adherence to multiple medications, assessed by electronic ©Morisky Widget MMAS-8 Software at the first visit (V1) and after 12 weeks (V2). A sub-analysis of intentional and unintentional non-adherence was performed. MUR impact was defined as the relative difference in ©MMAS-8 score after 12 weeks between the test and control group. A multiple linear regression model was used to predict MUR impact based on baseline adherence (low versus medium and high). Several secondary outcomes (e.g. evaluation of drug-related problems (DRPs)) were also assessed. Results Data from 153 (V1) and 140 (V2) patients were analysed. Baseline adherence was low, moderate and high in 17.6, 48.4 and 34.0% patients, respectively. In the low adherence subpopulation, test group patients showed a 1.20 point (95% CI = 0.16–2.25) increase in total ©MMAS-8 score (p = 0.025) compared to control group patients. A 0.84 point (95% CI = 0.05–1.63) increase was due to intentional non-adherence (p = 0.038), and a 0.36 point (95% CI = − 0.23-0.95) was due to unintentional non-adherence (p = 0.226). Additionally, statistically significant decrease in the proportion of patients with manifested DRPs (p < 0.001) and concerns regarding chronic medicines use (p = 0.029) were revealed. Conclusion MUR service in Slovenia improves low medication adherence and is effective in addressing DRPs and concerns regarding chronic medicines use. Trial registration ClinicalTrials.gov - NCT04417400; 4th June 2020; retrospectively registered.

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Effects of omega-3 supplementation on muscle damage after resistance exercise in young women: a randomized placebo-controlled trial

Nutrition and Health ◽

10.1177/02601060211022266 ◽

2021 ◽

pp. 026010602110222

Author(s):

Letícia Chisini Loss ◽

Diane Benini ◽

Felipe Xavier de Lima-e-Silva ◽

Gabriella Berwig Möller ◽

Luiza Rissi Friedrich ◽

...

Keyword(s):

Fish Oil ◽

Resistance Exercise ◽

Muscle Damage ◽

Young Women ◽

Muscle Soreness ◽

Controlled Trial ◽

Omega 3 ◽

Significant Group ◽

Balanced Diet ◽

Strength Capacity

Background: Omega-3 is a nutritional strategie that have been used to recover muscles from exercise-induced muscle damage in a preventive perspective. Aim: To verify whether omega-3 (ω-3) supplementation after a session of resistance exercise facilitates muscle recovery in women undergoing a balanced diet. Methods: This clinical trial was registered under the number NCT02839525. Thirty healthy women (22.2 ± 3.3 years) participated in this double-blinded, placebo-controlled trial. They were randomly distributed into ω-3 ( n=15) and placebo ( n=15) groups. They ingested ω-3 fish oil (3200 mg/day) or placebo (olive oil) at the dinner after the exercise bout (10 sets of 10 unilateral eccentric contractions in a knee extension chair), as well as at lunch for the three subsequent days. In addition, both groups followed a balanced diet along the four days. Muscle soreness and maximal isometric and isokinetic voluntary contractions were assessed immediately before, and 24, 48, and 72 hours after the resistance exercise. Main findings: There was no significant group-time interaction for any outcome. Participants presented increased levels of muscle soreness and reduced muscle strength capacity along the three days after exercise. There was no difference between placebo and ω-3 groups. Conclusion: Supplementation of ω-3 fish oil for three days after resistance exercise provided no additional benefits compared to placebo supplementation on recovery of healthy young women following a balanced diet.

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