Dolutegravir resistance in three pregnant and breastfeeding women in South Africa.
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ABSTRACT:
SUBMITTER: Fourie N
PROVIDER: S-EPMC10696620 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Publications
Dolutegravir resistance in three pregnant and breastfeeding women in South Africa.
Fourie Ninke N Rees Kate K Mali Denis D Mugisa Bridget B O'Connor Cara C Davies Natasha N
Southern African journal of HIV medicine 20231128 1
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Project description:ObjectiveHIV-uninfected pregnant and breastfeeding women are at high risk of HIV acquisition, contributing to vertical transmission of HIV. Preexposure prophylaxis (PrEP) is safe in pregnancy, but PrEP in pregnancy is not policy in many countries including South Africa. We evaluated the potential impact of providing PrEP for pregnant/breastfeeding women using a HIV model for South Africa.MethodsOur model considers two scenarios: a conservative scenario that matches the experience reported in the Kenyan PrEP programme for pregnant women (probability of uptake = 32% and 11% in high-risk and low-risk women, respectively); and an optimistic scenario with PrEP initiated by 80% of all pregnant women. We compared this with PrEP for female sex workers, MSM and adolescent girls/young women. Women are assumed to remain on PrEP throughout pregnancy and breastfeeding, and an equivalent average PrEP duration (2 years) is assumed in other scenarios.ResultsBetween 2020 and 2030, if PrEP is provided to pregnant/breastfeeding mothers, we project a 2.5% reduction in total HIV transmission [95% credibility interval (CI): 2.4-2.6%] in the conservative scenario and 7.2% (95% CI: 6.8-7.5%) in the optimistic scenario, which is similar to that in the female sex worker and MSM PrEP scenarios (1.9% and 3.0%, respectively). Without PrEP, 76 000 (95% CI: 64 000-90 000) new cases of vertical transmission are expected; PrEP provision may reduce these infections by 13% (95% CI: 13-14%) in the conservative scenario and 41% (95% CI: 39-44%) in the optimistic scenario.ConclusionHigh levels of uptake of and adherence to PrEP among pregnant/breastfeeding women could substantially reduce maternal and infant HIV acquisition in South Africa.
| S-EPMC6561341 | biostudies-literature
Project description:BackgroundDolutegravir resistance has been reported more frequently in patients with prior treatment experience compared to those on dolutegravir in first-line antiretroviral therapy (ART). The widespread use of dolutegravir in resource-limited programmatic settings might facilitate the emergence of resistance. Data on the prevalence of dolutegravir resistance from programmatic settings in Africa are scarce.MethodsThis retrospective observational cohort study assessed dolutegravir resistance in routine care settings of the Western Cape provincial public healthcare sector program between February 2021 and June 2024. Treatment-experienced adults who developed virologic failure (two HIV-1 RNA ≥1000 copies/mL), who had received dolutegravir-based ART for >24 months, were eligible for genotypic antiretroviral resistance testing (GART). Drug resistance mutations (DRMs) and resistance levels were classified using the Stanford database.ResultsAmong 99 eligible patients, 76 had GART performed, and 68 had successful sequences. Among these 68, 43 (63%) had dolutegravir DRMs with: 1 potential low, 1 low, 15 intermediate, and 26 high resistance levels. The median time on dolutegravir-based ART was 24 months (IQR, 23-31). Of the 43 patients with dolutegravir DRMs, 21 (49%) were receiving zidovudine-lamivudine-dolutegravir and 19 (44%) were receiving tenofovir-lamivudine-dolutegravir; 42/43 had prior ART experience.ConclusionsOver 60% of patients with prior treatment experience who had been on dolutegravir-based ART for over two years and experienced virologic failure had intermediate or high level dolutegravir resistance. This suggests that criteria for GART used are too stringent, which has resource implications in programmatic settings where access to resistance testing for individual management is limited.
| S-EPMC7617472 | biostudies-literature
Project description:BackgroundRising resistance of HIV-1 to non-nucleoside reverse transcriptase inhibitors (NNRTIs) threatens the success of the global scale-up of antiretroviral therapy (ART). The switch to WHO-recommended dolutegravir (DTG)-based regimens could reduce this threat due to DTG's high genetic barrier to resistance. We used mathematical modeling to predict the impact of the scale-up of DTG-based ART on NNRTI pretreatment drug resistance (PDR) in South Africa, 2020 to 2040.Methods and findingsWe adapted the Modeling Antiretroviral drug Resistance In South Africa (MARISA) model, an epidemiological model of the transmission of NNRTI resistance in South Africa. We modeled the introduction of DTG in 2020 under 2 scenarios: DTG as first-line regimen for ART initiators, or DTG for all patients, including patients on suppressive NNRTI-based ART. Given the safety concerns related to DTG during pregnancy, we assessed the impact of prescribing DTG to all men and in addition to (1) women beyond reproductive age; (2) women beyond reproductive age or using contraception; and (3) all women. The model projections show that, compared to the continuation of NNRTI-based ART, introducing DTG would lead to a reduction in NNRTI PDR in all scenarios if ART initiators are started on a DTG-based regimen, and those on NNRTI-based regimens are rapidly switched to DTG. NNRTI PDR would continue to increase if DTG-based ART was restricted to men. When given to all men and women, DTG-based ART could reduce the level of NNRTI PDR from 52.4% (without DTG) to 10.4% (with universal DTG) in 2040. If only men and women beyond reproductive age or on contraception are started on or switched to DTG-based ART, NNRTI PDR would reach 25.9% in 2040. Limitations include substantial uncertainty due to the long-term predictions and the current scarcity of knowledge about DTG efficacy in South Africa.ConclusionsOur model shows the potential benefit of scaling up DTG-based regimens for halting the rise of NNRTI resistance. Starting or switching all men and women to DTG would lead to a sustained decline in resistance levels, whereas using DTG-based ART in all men, or in men and women beyond childbearing age, would only slow down the increase in levels of NNRTI PDR.
| S-EPMC7735592 | biostudies-literature
Project description:BACKGROUND:Despite substantial progress in the delivery of HIV prevention programs, some communities continue to experience high rates of HIV infection. We report on temporal trends in HIV prevalence in pregnant women in a community in rural KwaZulu-Natal in South Africa. METHODS:Annual, anonymous cross-sectional HIV sero-prevalence surveys were conducted between 2001 and 2013 among first visit prenatal clinic attendees. The time periods 2001 to 2003 were defined as pre-antiretroviral therapy (ART), 2004 to 2008 as early ART, and 2009 to 2013 as contemporary ART roll-out, to correspond with the substantial scale-up of ART program. RESULTS:Overall, HIV prevalence rose from 35.3% [95% confidence interval (CI): 32.3 to 38.3] pre-ART (2001-2003) to 39.0% (95% CI: 36.8 to 41.1) in the early ART (2004-2008) to 39.3% (95% CI: 37.2 to 41.4) in the contemporary ART (2009-2013) roll-out periods. In teenage women (<20 years), HIV prevalence declined from 22.5% (95% CI: 17.5 to 27.5) to 20.7% (95% CI: 17.5 to 23.8) and to 17.2% (95% CI: 14.3 to 20.2) over the similar ART roll-out periods (P = 0.046). Prevalence increased significantly in women 30 years and older (P < 0.001) over the same time period largely because of survival after ART scale up. Teenage girls with male partners of age 20-24 and ? 25 years had a 1.7-fold (95% CI: 1.3-2.4; P = 0.001) and 3-fold (95% CI: 2.1 to 4.3; P < 0.001) higher HIV prevalence respectively. CONCLUSIONS:Notwithstanding the encouraging decline in teenagers, the ongoing high HIV prevalence in pregnant women in this rural community, despite prevention and treatment programs, is deeply concerning. Targeted interventions for teenagers, especially for those in age-disparate relationships, are needed to impact this HIV epidemic trajectory.
| S-EPMC5056320 | biostudies-literature
Project description:BackgroundCommunity-based peer support has been shown to be effective in improving exclusive breastfeeding rates in a variety of settings.MethodsWe conducted a cost analysis of a community cluster randomised-controlled trial (Promise-EBF), aimed at promoting exclusive infant feeding in three sites in South Africa. The costs were considered from the perspective of health service providers. Peer supporters in this trial visited women to support exclusive infant feeding, once antenatally and four times postpartum.ResultsThe total economic cost of the Promise-EBF intervention was US$393 656, with average costs per woman and per visit of US$228 and US$52, respectively. The average costs per woman and visit in an operational 'non research' scenario were US$137 and US$32 per woman and visit, respectively. Investing in the promotion of exclusive infant feeding requires substantial financial commitment from policy makers. Extending the tasks of multi-skilled community health workers (CHWs) to include promoting exclusive infant feeding is a potential option for reducing these costs. In order to avoid efficiency losses, we recommend that the time requirements for delivering the promotion of exclusive infant feeding are considered when integrating it within the existing activities of CHWs.DiscussionThis paper focuses on interventions for exclusive infant feeding, but its findings more generally illustrate the importance of documenting and quantifying factors that affect the feasibility and sustainability of community-based interventions, which are receiving increased focus in low income settings.
| S-EPMC3888383 | biostudies-literature
Project description:ObjectiveWe developed Healthy Families-PrEP to support perinatal women to use HIV prevention strategies.DesignSingle-arm study to evaluate PrEP use among pregnant women exposed to the intervention.MethodsWe offered safer conception counselling, including TDF/FTC as PrEP with adherence support (Healthy Families-PrEP) for women planning for pregnancy in South Africa with a partner with HIV or unknown serostatus. Women completed pregnancy and HIV testing quarterly and were followed for 1 year or until pregnancy end. For those initiating PrEP, electronic pillcap data and plasma were collected. We described PrEP adherence by proportion of days with pillcap openings and proportion of women with detected (≥10ng/ml) plasma tenofovir.ResultsFrom November 2017 to January 2020, 326 women with median age 24 years [interquartile range (IQR) 22-27] enrolled. Partner HIV-serostatus was unknown by 316 (97%). Over 3204 person-months of follow-up, 56 women became pregnant. Twenty-six women used PrEP during pregnancy and opened pillcaps on a mean of 53.1% [95% confidence interval (CI) 46.9-59.3%] of days. Plasma tenofovir was detected among 25, 15.4, and 12.5% of women providing samples during months 0-3, 4-6, and 7-9. No HIV seroconversions were observed.ConclusionWe observed low-pregnancy incidence. Counselling may have encouraged delayed pregnancy plans; some women may have exaggerated pregnancy plans to enroll. About half of pregnant women used PrEP and took over half of doses by pillcap. Fewer than 25% had tenofovir detected, likely reflecting pregnancy-related pharmacokinetics and adherence challenges. High interest in pregnancy PrEP use highlights the need to optimize adherence support and prevention choice.
| S-EPMC11902610 | biostudies-literature
Project description:IntroductionRapid diagnostic tests (RDTs) are the primary diagnostic tools for HIV used in resource-constrained settings. Without a proper confirmation algorithm, there is concern that false-positive (FP) RDTs could result in misdiagnosis of HIV infection and inappropriate antiretroviral treatment (ART) initiation, but programmatic data on FP are few.MethodsWe examined the accuracy of RDT diagnosis among HIV-infected pregnant women attending public sector antenatal services in Cape Town, South Africa. We describe the proportion of women found to have started on ART erroneously due to FP RDT results based on pre-ART viral load (VL) testing and enzyme-linked immunosorbent assay (ELISA).ResultsWe analysed 952 consecutively enrolled pregnant women diagnosed as HIV infected based on two RDTs per local guideline and found 4.5% (43/952) of pre-ART VL results to be <50 copies/ml. After excluding 6 women who had detectable virus on subsequent VL measurements, ELISA was performed on the 37 remaining women. Of these, 3/952 (0.3%) HIV RDT diagnoses were found to be FP. We estimate that using ELISA to confirm all positive RDTs would cost $1110 (uncertainty interval $381-$5382) to identify one patient erroneously initiated on ART, while it costs $3912 for a lifetime of antiretrovirals with VL monitoring for one person.ConclusionsCompared to the cost of confirming the RDT-based diagnoses, the cost of HIV misdiagnosis is high. While testing programmes based on RDT should strive for constant quality improvement, where resources permit, laboratory confirmation algorithms can play an important role in strengthening the quality of HIV diagnosis in the era of universal ART.
| S-EPMC5625589 | biostudies-literature
Project description:BackgroundDespite concerns about dolutegravir use in pregnancy, most low- and middle-income countries are accelerating the introduction of dolutegravir-based regimens into national antiretroviral treatment programmes. Questions remain about the acceptability of dolutegravir use in women due to the potential risks in pregnancy. This study from South Africa and Uganda explored community values, preferences and attitudes towards the use of dolutegravir-based regimens in women.MethodsThis study employed a qualitative design involving in-depth interviews and focus group discussion conducted between August 2018 to March 2019. The study was conducted in the months following an announcement of a potential risk for neural tube defects with dolutegravir use among women during conception and the first trimester. Participants included HIV positive pregnant and lactating women and their partners. They were selected purposively from urban poor communities in South Africa and Uganda. Data was analysed thematically in NVivo.ResultsForty-four in-depth interviews and 15 focus group discussions were conducted. Most participants had positive views of dolutegravir-based regimens and perceived it to be more desirable compared with efavirenz-containing regimens. There was widespread concern about use of dolutegravir during pregnancy and among women of childbearing age due to publicity around the possible association with neural tube defects. Acceptability was gendered, with nearly all male participants preferring their female spouses of childbearing potential not to use dolutegravir, while most women not planning pregnancy wanted access to contraception alongside dolutegravir. Community awareness and knowledge of dolutegravir was low and characterised by negative information. Women were concerned about HIV-related stigma and wanted the privacy features of dolutegravir to be strengthened with modification of the pill appearance and disguised packaging.ConclusionsDolutegravir-based regimens were found to be generally acceptable for use in women except during pregnancy. Interest in a dolutegravir-based regimen was linked with its perceived potential to enhance health, privacy and reduce stigma while concerns about neural tube defects were the main potential barrier to dolutegravir uptake in women. In order to optimise the community acceptability and uptake of acceptability-based regimen among women it is critical to strengthen community awareness and understanding of dolutegravir treatment, improve contraception services alongside the introduction of dolutegravir, and engage with male partners.
| S-EPMC7720619 | biostudies-literature
Project description:ObjectiveTo evaluate dolutegravir pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery.DesignOngoing, nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women and infants.MethodsIntensive steady-state 24 h pharmacokinetic profiles after dolutegravir 50 mg once-daily were performed during the second trimester (2T), third trimester (3T) and postpartum. Maternal delivery and postnatal infant samples were collected after birth. Dolutegravir was measured by validated LC-MS/MS; quantitation limit was 0.005 μg/ml. A two-tailed Wilcoxon signed-rank test (α = 0.10) was employed for paired within-subject comparisons.ResultsTwenty-nine enrolled participants had a median age of 32 years (range 21-42). Pharmacokinetic data were available for 15 (2T), 28 (3T) and 23 (postpartum) women. Median dolutegravir AUC0-24,Cmax and C24 were 25-51% lower in the 2T and 3T compared with postpartum. The median cord blood/maternal plasma concentration ratio was 1.25 (n = 18). In 21 infants, median elimination half-life was 32.8 h after in utero exposure. Viral load at delivery was less than 50 copies/ml for 27/29 women (93%). Twenty-nine infants were HIV-negative. Renal abnormalities noted on ultrasound in two infants were deemed possibly related to dolutegravir.ConclusionDolutegravir exposure is lower in pregnancy compared with postpartum in the same women on once-daily dosing. Median AUC0-24 during pregnancy was similar to, whereas trough concentrations were lower than, those seen in nonpregnant adults. Trough concentrations in pregnancy were well above dolutegravir EC90 (0.064 μg/ml). Dolutegravir readily crosses the placenta. Infant elimination is prolonged, with half-life over twice that of historical adult controls.
| S-EPMC5854536 | biostudies-literature
Project description:BackgroundTuberculosis (TB) is amongst the top five causes of death in women of childbearing age (15-≤44 years). Little is known about treatment of pregnant women with drug-resistant TB (DR-TB). Treatment for pregnant women remains challenging and more complex in DR-TB/HIV co-infection, where an evidence-based guide to clinical practice is limited. The study reviewed treatment and pregnancy outcomes and birth outcomes of their new-born in a cohort of pregnant women with DR-TB from three MDR-TB hospitals during 2010 and 2018.Design/methodsData were extracted from: TB register and patient clinic notes using a standardized case record form. Information on DR-TB treatment, pregnancy and Adverse Drug Events (ADEs) of twenty-six pregnant women treated with individualized second-line TB medications were captured. The frequency of favourable and adverse outcomes regarding disease and pregnancy were evaluated.ResultsThe mean age was 29 years (SD ±5.1), with the minimum and maximum age of 21 and 40 years, respectively. Eleven (42.3%) were previously treated with first-line TB drugs, 11 (42.3%) never treated before and 4 (15.4%) were previously treated for DR-TB. Of the 26 women, 15 (57.7%) had at least one ADE, but most had more than one ADE. Seventeen women were successfully treated, and 22 live births recorded. Live birth outcome was significantly associated with trimester of initiation of DR-TB treatment (p = 0.036). The proportion of live births for the pregnancy trimester when DR-TB treatment was initiated, were 60.0%, 90.9% and 100.0%, for first, second and third trimester, respectively.ConclusionDR-TB treatment should be delayed until after the first trimester. Routine pharmacovigilance surveillance integrated antenatal and delivery services with an integrated record of DR-TB treatment during pregnancy is recommended. Prospective studies using standardised case record forms for DR-TB treatment for pregnant women could provide more insight on the effect of DR-TB treatment on the birth outcome.
| S-EPMC7514075 | biostudies-literature