Efficacy and Safety of Tenofovir Disoproxil Fumarate Versus Low-Dose Stavudine Over 96 Weeks: A Multicountry Randomized, Noninferiority Trial

Venter, François; Kambugu, Andrew; Chersich, Matthew; Becker, Sophie; Hill, Andrew; Arulappan, Natasha; Moorhouse, Michelle; Majam, Mohammed; Akpomiemie, Godspower; Sokhela, Simiso; Poongulali, Selvamuthu; Feldman, Charles; Duncombe, Chris; Ripin, David H. Brown; Vos, Antonie; Kumarasamy, Nagalingeswaran

doi:10.1097/qai.0000000000001908

Cited by 13 publications

(13 citation statements)

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“…The second group consisted of participants on first-line ART. They were recruited from a RCT comparing two first-line ART regimens that had been completed in 2016 [ 18 ]. At the moment of inclusion in our study, participants were on a first-line tenofovir containing regimen for at least 2.5 years.…”

Section: Methodsmentioning

confidence: 99%

Electrocardiographic and echocardiographic abnormalities in urban African people living with HIV in South Africa

et al. 2021

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Background Studies from high income countries report that HIV-positive people have an impaired systolic and diastolic cardiac function compared to HIV-negative people. It is unclear if results can be translated directly to the Sub-Saharan Africa context. This study assesses electro- and echocardiographic characteristics in an urban African population, comparing HIV-positive people (treated and not yet treated) with HIV-negative controls. Methods We conducted a cross-sectional study in Johannesburg, South Africa. We enrolled HIV-positive participants from three randomized controlled trials that had recruited participants from routine HIV testing programs. HIV-negative controls were recruited from the community. Data were collected on demographics, cardiovascular risk factors, medical history and electrocardiographic and echocardiographic characteristics. Results In total, 394 HIV-positive participants and 153 controls were enrolled. The mean age of HIV-positive participants was 40±9 years (controls: 35±10 years), and 34% were male (controls: 50%). Of HIV-positive participants 36% were overweight or obese (controls: 44%), 23% had hypertension (controls: 28%) and 12% were current smoker (controls: 37%). Median time since HIV diagnosis was 6.0 years (IQR 2.3–10.0) and median treatment duration was 4.0 years (IQR 0.0–8.0), 50% had undetectable viral load. The frequency of anatomical cardiac abnormalities was low and did not differ between people with and without HIV. We observed no relation between HIV or anti-retroviral therapy (ART) and systolic or diastolic heart function. There was an association between ART use and corrected QT interval: +11.8 ms compared to HIV-negative controls (p<0.01) and +18.9 ms compared to ART-naïve participants (p = 0.01). We also observed a higher left ventricular mass index in participants on ART (+7.8 g/m2, p<0.01), but this association disappeared after adjusting for CD4 cell count, viral load and HIV-duration. Conclusion The low number of major cardiac abnormalities in this relatively young, well managed urban African HIV-positive population is reassuring. The increase in corrected QT interval and left ventricular mass may contribute to higher cardiac mortality and morbidity in people living with HIV in the long term.

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Section: Methodsmentioning

confidence: 99%

Electrocardiographic and echocardiographic abnormalities in urban African people living with HIV in South Africa

et al. 2021

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“…A cross-sectional study was conducted using the databases of two completed randomized controlled trials with participants diagnosed with HIV receiving ART, study 1: WRHI 052 [ 8 ] [NCT02671383] and study 2: WRHI 001 [ 9 ] [NCT02670772] (only patients recruited at the South African site were eligible for this study). The trial methods are published elsewhere [ 8 , 9 ]. The participants’ contact details were updated at every study visit for both trials.…”

Section: Methodsmentioning

confidence: 99%

Phone Calls to Retain Research Participants and Determinants of Reachability in an African Setting: Observational Study

et al. 2020

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Background Long-term retention of research participants in studies is challenging. In research in sub-Saharan Africa, phone calls are the most frequently used method to distantly engage with participants. Objective We aimed to get insight into the effectiveness of phone calls to retain contact with participants and evaluated determinants of reachability. Methods A cross-sectional study was performed using the databases of two randomized controlled trials investigating different kinds of antiretroviral therapy in HIV-positive patients. One trial finished in 2018 (study 1), and the other finished in 2015 (study 2). A random sample size of 200 participants per study was obtained. There were up to 3 phone numbers available per participant collected during the studies. Participants received a maximum of 3 phone calls on every available number on different days and at different times. Voicemails were left, and emails sent wherever possible. We documented how many calls were answered, who answered, as well as after how many attempts participants were reached. To further increase our understanding of reachability, we conducted a short questionnaire assessing factors contributing to reachability. The study was approved by the Research Ethics Committee of the University of Witwatersrand, Johannesburg, South Africa (reference number M1811107). Results In our sample size of n=200 per study, study 1, with a median time of 11 months since the last visit at the research site, had a response rate of 70.5% (141/200) participants while study 2, with a median duration of 55 months since the last visit, had a response rate of 50.0% (100/200; P<.001). In study 1, 61.5% (123/200) of calls were answered directly by the participant while this was 36.0% (72/200) in study 2 (P=.003). The likelihood of reaching a participant decreased with time (odds ratio [OR] 0.73, 95% CI 0.63 to 0.84) for every year since the last face-to-face visit. Having more phone numbers per participant increased reachability (OR 2.32, 95% CI 1.24 to 4.36 for 2 phone numbers and OR 3.03, 95% CI 1.48 to 6.22 for 3 phone numbers compared with 1 number). A total of 141 of 241 reached participants responded to the questionnaire. Of the 93 participants who had changed phone numbers, 5% (50/93) had changed numbers because their phone was stolen. The most preferred method of being contacted was direct calling (128/141) with participants naming this method followed by WhatsApp (69/141). Conclusions Time since last visit and the number of phone numbers listed were the only determinants of reachability. Longer follow-up time is accompanied with a decrease in reachability by phone while more listed phone numbers increases the likelihood that someone can be reached. Trial Registration ClinicalTrials.gov NCT02671383; https://clinicaltrials.gov/ct2/show/NCT02671383 and ClinicalTrials.gov NCT02670772; https://clinicaltrials.gov/ct2/show/NCT02670772

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“…A randomised 1:1 double blind placebo-controlled trial was conducted in Johannesburg, South Africa, Kampala, Uganda and Chennai, India to assess the efficacy and safety of treatment with either low dose stavudine (20 mg twice a day) or tenofovir (300 mg daily) tablets administered in combination with lamivudine (150 mg BD) and efavirenz (600 mg daily) over 96 weeks (Clinicaltrials.gov, NCT02670772). The methods including quality control and safety evaluation are described in detail elsewhere [17]. In brief, data were captured in an electronic data system.…”

Section: Methodsmentioning

confidence: 99%

“…Between 2012 and 2016, a clinical trial was initiated, comparing a lower dose of stavudine to the current most commonly used first-line drug, tenofovir disoproxil fumarate (’tenofovir’). The overall conclusion was that low-dose stavudine was equally effective as tenofovir in reducing viral load after 48 weeks, but that lipoatrophy occurred more often in the low-dose stavudine group [17]. Extensive metabolic and toxicity monitoring allow us to conduct an in-depth analysis of the effects of ART initiation with low-dose stavudine or tenofovir on lipid levels, insulin resistance and CVD risk, an important analysis as the vast majority of people on ART are taking regimens containing tenofovir.…”

Section: Introductionmentioning

confidence: 99%

Lipid levels, insulin resistance and cardiovascular risk over 96 weeks of antiretroviral therapy: a randomised controlled trial comparing low-dose stavudine and tenofovir

et al. 2018

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BackgroundHIV infection and antiretroviral treatment are associated with changes in lipid levels, insulin resistance and risk of cardiovascular disease (CVD). We investigated these changes in the first 96 weeks of treatment with low-dose stavudine or tenofovir regimens.MethodsThis is a secondary analysis of a double blind, randomised controlled trial performed in South-Africa, Uganda and India comparing low-dose stavudine (20 mg twice daily) with tenofovir in combination with efavirenz and lamivudine in antiretroviral-naïve adults (n = 1067) (Clinicaltrials.gov, NCT02670772). Over 96 weeks, data were collected on fasting lipids, glucose and insulin. Insulin resistance was assessed with the HOMA-IR index and 10-year CVD risk with the Framingham risk score (FRS). A generalized linear mixed model was used to estimate trends over time.ResultsParticipants were on average 35.3 years old, 57.6% female and 91.8% Black African. All lipid levels increased following treatment initiation, with the sharpest increase in the first 24 weeks of treatment. The increase in all lipid subcomponents over 96 weeks was higher among those in the stavudine than the tenofovir group. Insulin resistance increased steadily with no difference detected between study groups. FRS rose from 1.90% (1.84–1.98%) at baseline to 2.06 (1.98–2.15%) at week 96 for the total group, with no difference between treatment arms (p = 0.144). Lipid changes were more marked in Indian than African participants.ConclusionLipid levels increased in both groups, with low-dose stavudine resulting in a worse lipid profile compared to tenofovir. Insulin resistance increased, with no difference between regimens. CVD risk increased over time and tended to increase more in the group on stavudine. The low CVD risk across both arms argues against routine lipid and glucose monitoring in the absence of other CVD risk factors. In high risk patients, monitoring may only be appropriate at least a year after treatment initiation.Electronic supplementary materialThe online version of this article (10.1186/s12977-018-0460-z) contains supplementary material, which is available to authorized users.

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Efficacy and Safety of Tenofovir Disoproxil Fumarate Versus Low-Dose Stavudine Over 96 Weeks: A Multicountry Randomized, Noninferiority Trial

Abstract: Supplemental Digital Content is Available in the Text.

Cited by 13 publications

References 38 publications

Electrocardiographic and echocardiographic abnormalities in urban African people living with HIV in South Africa

Electrocardiographic and echocardiographic abnormalities in urban African people living with HIV in South Africa

Phone Calls to Retain Research Participants and Determinants of Reachability in an African Setting: Observational Study

Lipid levels, insulin resistance and cardiovascular risk over 96 weeks of antiretroviral therapy: a randomised controlled trial comparing low-dose stavudine and tenofovir

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