Vaginal microbial shifts are unaffected by oral pre-exposure prophylaxis in South African women.
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ABSTRACT:
SUBMITTER: Mazibuko-Motau N
PROVIDER: S-EPMC9519742 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
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Vaginal microbial shifts are unaffected by oral pre-exposure prophylaxis in South African women.
Mazibuko-Motau Noluthando N Sobia Parveen P Xu Jiawu J Elsherbini Joseph Ahmed JA San James E JE Lewis Lara L Mtshali Andile A Mzobe Gugulethu G Ntuli Lungelo L Abdool Karim Salim S SS Mansoor Leila E LE Abdool Karim Quarraisha Q Kwon Douglas S DS Archary Derseree D Ngcapu Sinaye S
Scientific reports 20220928 1
Vaginal microbiota have been shown to be a modifier of protection offered by topical tenofovir in preventing HIV infection in women, an effect not observed with oral tenofovir-based pre-exposure prophylaxis (PrEP). It remains unclear whether PrEP can influence the vaginal microbiota composition. This study investigated the impact of daily oral tenofovir disoproxil fumarate in combination with emtricitabine for PrEP on the vaginal microbiota in South African women. At baseline, Lactobacillus iner ...[more]
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Project description:BackgroundIn VOICE, a multisite HIV pre-exposure prophylaxis (PrEP) trial, plasma drug levels pointed to widespread product nonuse, despite high adherence estimated by self-reports and clinic product counts. Using a socio-ecological framework (SEF), we explored socio-cultural and contextual factors that influenced participants' experience of daily vaginal gel and oral tablet regimens in VOICE.MethodsIn Johannesburg, a qualitative ancillary study was concurrently conducted among randomly selected VOICE participants assigned to in-depth interviews (n = 41), serial ethnographic interviews (n = 21), or focus group discussions (n = 40). Audiotaped interviews were transcribed, translated, and coded thematically for analysis.ResultsOf the 102 participants, the mean age was 27 years, and 96% had a primary sex partner with whom 43% cohabitated. Few women reported lasting nonuse, which they typically attributed to missed visits, lack of product replenishments, and family-related travel or work. Women acknowledged occasionally skipping or mistiming doses because they forgot, were busy, felt lazy or bored, feared or experienced side effects. However, nearly all knew or heard of other study participants who did not use products daily. Three overarching themes emerged from further analyses: ambivalence toward research, preserving a healthy status, and managing social relationships. These themes highlighted the profound and complex meanings associated with participating in a blinded HIV PrEP trial and taking antiretroviral-based products. The unknown efficacy of products, their connection with HIV infection, challenges with daily regimen given social risks, lack of support-from partners and significant others-and the relationship tradeoffs entailed by using the products appear to discourage adequate product use.ConclusionsPersonal acknowledgment of product nonuse was challenging. This qualitative inquiry highlighted key influences at all SEF levels that shaped women's perceptions of trial participation and experiences with investigational products. Whether these impacted women's behaviors and may have contributed to ineffective trial results warrants further investigation.
| S-EPMC3931679 | biostudies-literature
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.
| S-EPMC11829381 | biostudies-literature
Project description:BackgroundHIV 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.MethodsECHO, 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.ResultsOf 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).ConclusionsOver 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 numberNCT02550067.
| S-EPMC9377486 | biostudies-literature
Project description:ObjectiveTo estimate the effect of intimate partner violence (IPV) on oral pre-exposure prophylaxis (PrEP) adherence among adolescent girls and young women (AGYW).DesignWe conducted a secondary analysis of data from HIV Prevention Trials Network 082 (HPTN 082), a multisite prospective study designed to assess oral PrEP adherence among AGYW in southern Africa.MethodsWe estimated the relative prevalence of high PrEP adherence 3 and 6 months after initiation among AGYW 16-25 years who reported a history of any IPV in the past year at enrollment versus AGYW who did not, both overall and by age. High adherence was defined as an intracellular tenofovir-diphosphate concentration at least 700 fmol/punch or more dried blood spots.ResultsAmong 409 PrEP-initiating AGYW, half (49%) reported experiencing any IPV by a current/recent partner in the year prior to enrollment. Overall, a similar proportion of AGYW who reported IPV had high PrEP adherence at months 3 and 6 as AGYW who did not report IPV. There was, however, evidence of effect modification by age at month 3: among AGYW less than 21 years old, those who reported IPV were less than half as likely to have high adherence [adjusted PR (aPR) = 0.43, 95% confidence interval (CI) 0.22-0.86]; among AGYW aged 21 years or older, those who reported IPV were more than twice as likely to have high adherence (aPR = 2.21, 95% CI 1.34-3.66). At month 6, effect estimates within each age stratum were consistent in direction to those at month 3.ConclusionIPV events may either impede or motivate PrEP adherence among African AGYW, with age appearing to be an important consideration for IPV-related adherence interventions.
| S-EPMC9486991 | biostudies-literature
Project description:Since the introduction of oral pre-exposure prophylaxis (PrEP) in 2016, countries have successfully scaled-up PrEP to populations at risk of HIV acquisition, including key populations, serodiscordant couples and pregnant women. Between 2016 and 2023, there were over 5.6 million oral PrEP initiations globally. Of these, over 1.2 million occurred in South Africa, with nearly 700,000 implemented through USAID/South Africa's PEPFAR program. This case study uses WHO's Building Blocks for Health Systems Strengthening to describe USAID's oral PrEP program in South Africa, reporting experiences and lessons learned in 14 districts across 7 provinces. Key lessons include: (i) Substantial donor financial investment was critical for expanding oral PrEP in South Africa, but sustained leadership and investment from government stakeholders, such as the Department of Health and the National Treasury, have been essential for sustainability. Despite fluctuations in USAID funding, annual PrEP initiations have continued to increase in USAID-supported districts largely due to local leadership. (ii) Health information and supply chain systems required agility to monitor oral PrEP introduction and scale-up. When systems lacked agility, temporary solutions like the development of interim reporting tools were necessary. (iii) Integrating community-based and facility-based service delivery supported client-centered care. Nurses and lay health workers contributed to over 80% of the full-time equivalents supporting PrEP under USAID's human resources for health portfolio. (iv) Integrating sexual and reproductive health services with oral PrEP service delivery provided clients with comprehensive, client-centered care. (v) Other client-centered care included differentiated service delivery options, such as mobile and gazebo modalities, and expanded PrEP choice through implementation science activities for new PrEP products. (vi) USAID-supported PrEP initiations have been highest among females of reproductive age in the general population and men who have sex with men among key populations, priority populations in South Africa. As done in this case study, sharing best practices and lessons learned from USAID/South Africa's oral PrEP program can strengthen the implementation evidence base and inform more efficient PrEP service delivery, particularly as new PrEP products become available.
| S-EPMC11666530 | biostudies-literature
Project description:IntroductionThere is limited understanding of how social dynamics impact pre-exposure prophylaxis (PrEP) adherence among adolescent girls and young women (AGYW) in generalized HIV-epidemic settings. We examined experiences of oral PrEP use disclosure to various social groups with the goal of identifying supportive relationships that can be leveraged to promote adherence.MethodsWe used qualitative methods to explore experiences disclosing PrEP use and the perceived impact of disclosure on adherence among 22 South African AGYW (16-25 years) taking daily oral PrEP. Serial in-depth-interviews (IDIs) were conducted 1-, 3-, and 12-months post-PrEP initiation. Respondents also self-reported their disclosures separately for various social groups and adherence was assessed using intracellular tenofovir-diphosphate levels.ResultsQualitative respondents had a median age of 20.5 years and reported disclosing their PrEP use to friends (n = 36 total disclosures), partners, siblings, other family members (n = 24 disclosures each), and parents (n = 19 disclosures). IDI data revealed that parents and partners provided the most support to respondents and a lack of support from these groups was most often perceived as negatively affecting PrEP use. AGYW described difficulties explaining PrEP to their mothers, who believed PrEP was HIV treatment or would lead to HIV infection. Disclosure to household members was notably meaningful for AGYW (both positively and negatively). Respondents reported leveraging supportive relationships for pill reminders. For respondents who perceived a household member would be unsupportive, however, non-disclosure was less feasible and PrEP use was often stigmatized. To avoid stigma, several respondents hid or discontinued PrEP.ConclusionsWhile supportive relationships may facilitate PrEP use, disclosure can also lead to stigma. Counselors should support AGYW in disclosing to key people in their social networks and provide AGYW with materials that lend credibility to explanations of PrEP. Community education is necessary to alleviate PrEP-related stigma and facilitate disclosure.
| S-EPMC7935254 | biostudies-literature
Project description:BackgroundDespite the established efficacy of PrEP to prevent HIV and the advantages of a user-controlled method, PrEP uptake and persistence by women in both trials and demonstration projects has been suboptimal. We utilized real-world data from an HIV service provider to describe persistence on oral PrEP among female sex workers (FSW) in eThekwini, South Africa.MethodsWe examined time from PrEP initiation to discontinuation among all FSW initiating PrEP at TB HIV Care in eThekwini between 2016-2020. We used a discrete time-to-event data setup and stacked cumulative incidence function plots, displaying the competing risks of 1) not returning for PrEP, 2) client discontinuation, and 3) provider discontinuation. We calculated hazard ratios using complementary log-log regression and sub-hazard ratios using competing risks regression.ResultsThe number of initiations increased each year from 155 (9.3%, n = 155/1659) in 2016 to 1224 (27.5%, n = 1224/4446) in 2020. Persistence 1-month after initiation was 53% (95% CI: 51%-55%). Younger women were more likely to discontinue PrEP by not returning compared with those 25 years and older. Risk of discontinuation through non-return declined for those initiating in later years. Despite the COVID-19 pandemic, a greater number of initiations and sustained persistence were observed in 2020.ConclusionsLow levels of PrEP persistence were observed, consistent with data among underserved women elsewhere. Encouragingly, the proportion of women persisting increased over time, even as the number of women newly initiating PrEP and staff workload increased. Further research is needed to understand which implementation strategies the program may have enacted to facilitate these improvements and what further changes may be necessary.
| S-EPMC8923438 | biostudies-literature
Project description:BackgroundLong-acting injectable and implantable approaches aim to overcome some of the documented challenges with uptake and adherence to current HIV prevention methods. Youth are a key end-user population for these methods. We used qualitative methods to examine product attributes and preferences for current and future long-acting HIV prevention approaches.MethodsNinety-five South African youth aged 18-24 years, of whom 62 were female and 33 male, completed 50 interviews and 6 focus groups. We purposively selected for previous product experience, including oral pre-exposure prophylaxis, injectable pre-exposure prophylaxis, or the vaginal ring, to ensure participants' opinions were rooted in actual experience.ResultsIrrespective of previous method-use experience, gender, or sexual orientation, the majority expressed a preference for prevention methods formulated as injectables or implants. Several mentioned that their top priority in any product was efficacy, and for some, this overrode other concerns; for example, even if they feared pain, an implant or an injectable would be used if fully protective. Although efficacy was a top priority, there was also a clear desire across all subgroups for a product that would not interfere with sex, would stay in the system to provide protection, and that caused minimal burden, or was not apparent to others, and these characteristics were most salient for long-acting methods.ConclusionsNarrative explanations for preferences converged thematically around different dimensions of "invisibility" including invisibility to oneself, one's partner and household members, and community members. End-user preferences can be used to inform product development of long-acting HIV prevention approaches formulated as injections or implants to optimize adherence and impact.
| S-EPMC6426447 | biostudies-literature
Project description:To assess the potential uptake of HIV pre-exposure prophylaxis (PrEP) products among female sex workers (FSWs) vulnerable to HIV infection, we examined the influence of product attributes on willingness to use products among 271 HIV-negative FSWs in Tijuana and Ciudad Juarez, Mexico (2016-2017). Via five-point Likert scale ratings, participants indicated their willingness to use hypothetical products with six attributes: formulation (pill, gel, liquid, or ring), frequency of use (daily, on-demand, or monthly), cost per use (10 or 200 pesos), effectiveness (40% or 80%), side effects (none or mild), and access point (healthcare clinic or non-governmental organization). Conjoint analysis was used to determine the impact of attributes on product ratings and identify preferred product attributes. Multinomial logistic regression was used to identify factors associated with formulation preferences. In both cities, formulation and frequency of use had the greatest impact on ratings. Participants in Ciudad Juarez indicated a strong preference for oral pills, whereas participants in Tijuana indicated roughly equal preferences for oral pills and vaginal gels. Monthly product use was preferred in both cities. Compared to preferring oral pills (38%), preferring vaginal gels (28%) was associated with practicing vaginal lubrication (adjusted odds ratio = 2.08; 95% confidence interval: 1.07-4.04). Oral PrEP may be acceptable to many FSWs in Tijuana and Ciudad Juarez; however, continued development of behaviorally-congruent vaginal PrEP products may also facilitate uptake and ensure sufficient coverage.
| S-EPMC6391168 | biostudies-literature
Project description:IntroductionOral tenofovir disoproxil fumarate/emtricitabine pre-exposure prophylaxis (PrEP), introduced into South Africa (SA) in 2016, has increasingly become part of HIV prevention standard of care. Given the urgent need for increased HIV prevention efforts for young women in SA, we conducted an implementation study to explore oral PrEP initiation and adherence, and the impact of oral PrEP on HIV incidence in this group.MethodsThis prospective cohort study (CAPRISA 082) was conducted at two sites (urban and rural) in KwaZulu-Natal, between March 2016 and February 2018. HIV-negative, sexually active women, aged 18-30 years, were enrolled and followed for approximately 10 months. Oral PrEP was offered as part of a comprehensive HIV prevention package. Adherence to oral PrEP was measured using pill counts and tenofovir-diphosphate (TFV-DP) levels. Characteristics of oral PrEP initiators versus non-initiators were compared using risk ratios. HIV incidence rates were measured using Poisson regression.ResultsOf 425 women enrolled, 262 (62%) initiated oral PrEP. Uptake was significantly higher at the rural site compared to the urban site (78% [n = 203/259] vs. 36% [n = 59/166], respectively, p-value<0.001). Approximately 25% and 50% had stopped using oral PrEP by 3 and 12 months post-initiation, respectively. Median pill count adherence was 90% (interquartile range: 81-97%); however, TFV-DP was only detected in 13% of samples tested, that is 56/431 samples from 97 (37%) participants who initiated oral PrEP. In total, 11 women seroconverted yielding an HIV incidence rate of 2.81 per 100 person-years (95% confidence interval: 1.40-5.03). Nine of 11 seroconverters had initiated oral PrEP; however, all showed drug levels equivalent to taking one to zero tablets per week. Among women who initiated oral PrEP, >50% had discontinued using oral PrEP by study end, with side effects, such as diarrhoea, nausea, headaches and rash, being the most frequent reason for discontinuation.ConclusionsDespite moderate oral PrEP initiation and high pill count adherence, adherence as measured by TFV-DP levels was low and early discontinuation was high. The overall HIV incidence rate was high underscoring the critical need to address barriers to oral PrEP initiation, adherence and continued use, as well as expanding HIV prevention options for young women.
| S-EPMC9251857 | biostudies-literature