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Higher rates of metabolic syndrome among women taking zidovudine as compared to tenofovir in rural Africa: preliminary data from the CART-1 study.

ABSTRACT: Due to its side effects stavudine (D4T) has been replaced by zidovudine (AZT) and tenofovir (TDF) in most low- and middle-income countries (LMICs). In 2014 about 38% of adult first-line regimens contain AZT and 62% TDF [1]. Whereas the unfavourable metabolic outcomes of D4T in comparison to TDF have been described extensively, studies from LMICs comparing metabolic profiles between patients on AZT and TDF are scarce. Given the high number of patients in LMICs still taking AZT, data on their metabolic profile are needed. We present rates of metabolic syndrome (MS) in adult patients taking either AZT- or TDF-containing first-line, non-nucleoside reverse transcriptase (NNRTI)-based regimens.Data derived from a cross-sectional multi-disease screening conducted in ten facilities in two rural districts of Lesotho, Southern Africa [2]. Patients were eligible if aged ?25 years and on NNRTI-containing first-line ART ?6 months. The MS definition for Africa of the International Diabetes Federation was applied [3]. Assessed potential predictors for MS were age, time on ART, virologic suppression, body-mass index (BMI), alcohol consumption, wealth quintile, NNRTI (nevirapine (NVP) or Efavirenz (EFV)), history of previous D4T exposure and ART-backbone (AZT or TDF). Statistical analyses - stratified for sex - comprised univariate logistic regression for each predictor variable with subsequent construction of a multivariate model including all predictors with an association to MS at a significance level<0.1 in univariate analysis.Out of 1026 patients, 660 (64.3%) were female. MS prevalence was 9.8% (95% CI 6.9-13.4) in men and 22.9% (19.7-26.3) in women. In women, aged ?35 years, AZT-backbone, NVP-base, BMI ?25kg/m2 and taking ART for ?4.5 years were associated with MS in univariate analysis. In the multivariate model only AZT (adjusted odds-ratio: 2.2, 95% CI 1.4-3.6; p=0.001) and BMI ?25kg/m2 (9.8; 2.8-34.1, p<0.001) were associated with MS. For men, age, higher wealth quintile, history of D4T exposure and BMI were associated with MS in univariate analysis. In the multivariate model only a BMI ?25kg/m2 was associated with MS (8.9; 3.8-20.9, p<0.001).In rural Lesotho, Southern Africa, the use of AZT instead of TDF among women who are on ART for ?6 months predisposes to the development of metabolic syndrome. Given that, still 38% of first-line regimens in LMIC contain AZT, this finding needs to be verified in other settings in Sub-Saharan Africa.

SUBMITTER: Labhardt ND

PROVIDER: S-EPMC4224833 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Higher rates of metabolic syndrome among women taking zidovudine as compared to tenofovir in rural Africa: preliminary data from the CART-1 study.

Labhardt Niklaus Daniel ND Cheleboi Molisana M Faturyiele Olatunbosun O Motlatsi Mokete M MM Pfeiffer Karolin K Lejone Thabo Ismael TI Cerutti Bernard B Muser Jürgen J Gupta Ravi Shankar RS Lynen Lutgarde L Hatz Christoph C

Journal of the International AIDS Society 20141102 4 Suppl 3

<h4>Introduction</h4>Due to its side effects stavudine (D4T) has been replaced by zidovudine (AZT) and tenofovir (TDF) in most low- and middle-income countries (LMICs). In 2014 about 38% of adult first-line regimens contain AZT and 62% TDF [1]. Whereas the unfavourable metabolic outcomes of D4T in comparison to TDF have been described extensively, studies from LMICs comparing metabolic profiles between patients on AZT and TDF are scarce. Given the high number of patients in LMICs still taking AZ ...[more]

PMID: 25394059

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Project description:In 2013, the World Health Organization (WHO) recommended scaling up of routine viral load (VL) monitoring for patients on antiretroviral therapy (ART) in resource-limited settings [1]. During the transition phase from no VL-testing at all to routine VL-monitoring, targeted VL for groups at particular risk of virologic failure (VF) may be an option [2]. We present socio-demographic and clinical risk factors for VF in a cohort in rural Lesotho with no access to VL prior to the study.Data derive from a cross-sectional study providing multi-disease screening as well as VL testing to adult patients (?16 years old) on first-line ART ?6 months [3]. VF was defined as VL?1000 copies/mL. Assessed potential predictors of VF were: (1) socio-demographic (sex, age, wealth-quintile, education, employment status, disclosure of HIV status to environment, travel-time to facility); (2) treatment history (history of treatment interruption >2 days, previous drug substitution within first-line ART, time on ART, ART-base and -backbone); (3) adherence (pill count) and (4) clinical (clinical or immunological failure as defined by WHO guidelines [1], presence of papular pruritic eruption (PPE)). All variables with association to VF in univariate analysis were included in a multivariate logistic regression reporting adjusted Odds ratios (aOR).Data from 1,488 patients were analyzed. Overall VF-prevalence was 6.9% (95% CI 5.7-8.3). In univariate analysis, the following were associated with VF: age <30, lower wealth-quintile, no primary education, history of treatment interruption, nevirapine-base, zidovudine-backbone, history of drug substitution, travel-time to clinic ?2 hours, disclosure of HIV status to <5 persons, clinical failure, presence of PPE and immunological failure. In multivariate analysis, 6 out of the above 12 variables were independent predictors: age <30 years (aOR: 2.4; 95% CI 1.1-5.3, p=0.029), history of treatment interruption (2.5; 1.3-4.7, p=0.005), PPE (6.9; 2.5-18.9, p<0.001), immunological failure (11.5; 5.7-23.2, p<0.001), history of drug substitution (1.9; 1.0-3.7, p=0.043), disclosure of HIV status to <5 persons (1.8; 1.1-3.1, p=0.03).In this cohort in rural Lesotho, several socio-demographic and clinical predictors were associated with VF. Particularly age <30 years, history of treatment interruption, PPE and immunological failure were strongly associated with VF. These patients may be prioritized for targeted VL-testing.

Project description:BackgroundAlthough tenofovir (TDF)/emtricitabine (FTC)/efavirenz (EFV) and zidovudine (ZDV)/lamivudine (3TC)/efavirenz (EFV) are used as preferred first line regimen, their head-to-head comparison in terms of their efficacy and tolerability was limited. This review aimed to synthesize the best available evidence on the comparative efficacy and tolerability of the two regimens.MethodsSeven sites and databases in addition to Google search until August 20, 2016, were searched. Only randomized clinical trials conducted on adult population were included in this study. Our primary outcome was viral load suppression while secondary outcomes were death and tolerability. Undetectable viral load is defined as <50 Human Immunodeficiency Virus (HIV) ribonucleic acid (RNA) copies/ml. Joanna Briggs institute meta-analysis of statistics assessment and review instrument (JBI-MAStARI) and critical appraisal and data extraction tool were applied for critical assessment and data extraction, respectively. We performed a random effect meta-analysis to pool the relative risk (RR) for viral load suppression (<50 HIV RNA copies/ml and <400 HIV RNA copies/ml), tolerability, and death.ResultData was extracted from four articles, which included a total of 2381 participants. We found superior viral load suppression among tenofovir (TDF) arm compared to zidovudine (ZDV) arm. Tenofovir arm achieves viral load <50 HIV RNA copies/ml (RR = 1.12, 95% confidence interval (CI) [1.04, 1.21], I2 = 0%) higher than zidovudine arm. Similarly TDF arm is superior in viral load suppression to <400 HIV RNA copies/ml (RR = 1.19, 95% CI [1.11, 1.27], I2 = 0%). Moreover, TDF based regimens were more likely to be tolerated than ZDV based regimens (4 trials, 2381 participants (RR = 1.06, 95% CI [1.02, 1.10], I2 = 51%)). However, forest plot of death shows that it was not significant (RR = 0.91, 95% CI [0.51, 1.62]).ConclusionThe use of TDF/FTC/EFV as first line regimen for naïve HIV-1 infected adult patient showed superior viral load suppression and tolerability as compared to ZDV/3TC/EFV. In order to compare the death outcome of both ZDV/3TC/EFV and TDF/FTC/EFV further research is needed.

Project description:Background: HIV pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine is effective when taken daily. Previously, we developed a urine assay capable of detecting the prodrug tenofovir (TFV) in patients taking tenofovir disoproxil fumarate (TDF)-based PrEP. However, tenofovir alafenamide (TAF) has replaced TDF due to its different safety profile for HIV treatment and was recently approved as PrEP. Given the need to ensure the aforementioned assay remains available for the purpose of objective adherence monitoring, it is critical to ensure its accuracy for detecting TFV in patients taking TAF. Methods: Blood and urine samples were collected from 3 cohorts of patients: (1) 10 participants living with HIV (PLWH) with suppressed virus on a TAF-based regimen, (2) 10 HIV-participants administered 1 dose of TAF/FTC followed by urine and plasma sampling for 7 days starting 1-3 h post-dose, and (3) 10 HIV-participants administered 7 doses of TAF/FTC followed by urine and plasma sampling for 10 days starting 1-3 h after the last dose. Samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with high sensitivity and specificity for TFV. HIV-samples were compared to a historical cohort administered one dose of TDF/FTC. Results: PLWH were 90% male, 40% African American, and 10% Hispanic (mean age = 57 y; SD 8.88 y). HIV-participants were 55% male and 70% Caucasian (mean age = 31.6 y; SD 7.70 y). Samples from PLWH demonstrated TFV concentrations 2 logs higher in urine than plasma (1,000 ng/mL vs ±10 ng/mL) at the time of collection. Urine samples following a single dose of TAF in HIV-participants yielded TFV concentrations ranging from 100 to 1,000 ng/mL 1-3 h post-dose and remained >100 ng/mL for 6 days in 8 of 10 participants. Urine samples collected after 7 consecutive doses of TAF yielded TFV concentrations >1,000 ng/mL 1-3 h after dosing discontinuation, with TFV concentrations >1,00 ng/mL 7 days post discontinuation in 8 of 10 participants. Urine TFV concentrations following TAF administration were comparable to those from a historical cohort administered TDF/FTC. Plasma TFV concentrations were low(±10 ng/mL) in both HIV-cohorts at all time points. Conclusions: TFV persists in urine at detectable concentrations in participants taking TAF/FTC for at least 7 days despite largely undetectable plasma concentrations, with urine TFV concentrations comparable to patients taking TDF/FTC. This study demonstrates the ability of a urine TFV assay to measure recent TAF adherence.

Dataset Information

Higher rates of metabolic syndrome among women taking zidovudine as compared to tenofovir in rural Africa: preliminary data from the CART-1 study.

Publications

Higher rates of metabolic syndrome among women taking zidovudine as compared to tenofovir in rural Africa: preliminary data from the CART-1 study.

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