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Early upper digestive tract side effects of zidovudine with tenofovir plus emtricitabine in West African adults with high CD4 counts.

ABSTRACT: Tenofovir (TDF) with emtricitabine (FTC) and zidovudine (ZDV) is a recognized alternate first-line antiretroviral (ART) regimen for patients who cannot start treatment with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Clinical studies comparing TDF+FTC+ZDV to other regimens are lacking.Participants in a trial of early ART in Côte d'Ivoire (Temprano ANRS 12136) started treatment with TDF/FTC plus either efavirenz (EFV) or ZDV (HIV-1+2 dually infected patients and women refusing contraception or previously treated with nevirapine). We compared rates of upper digestive serious adverse events (sAEs) between TDF/FTC+EFV and TDF/FTC+ZDV patients during the first six months of treatment. sAEs were defined as either grade 3-4 AEs or persistent grade 1-2 AEs leading to drug discontinuation.A total of 197 patients (76% women, median CD4 count 395/mm(3)) started therapy with TDF/FTC, 126 with EFV and 71 with ZDV. During the first six months of ART, 94 patients had digestive AEs (nausea/vomiting) of any grade (EFV 36/126, 29%; ZDV 58/71, 82%, p<0.0001), including 20 sAEs (EFV 3/126, 5%; ZDV 17/71, 24%, p<0.0001). In-patients on TDF/FTC+ZDV with digestive AEs, the median time to the first symptom was two days (IQR: 1-4). Plasma ZDV (Cmax) distributions and pill ZDV dosages were normal. Patients with digestive AEs had higher haemoglobin levels and tended to have higher body mass indices and more frequent past histories of cotrimoxazole (CTX) prophylaxis.We observed an unexpectedly high rate of digestive sAEs in West African adults, mostly women, who started a 3-nuc ART with TDF/FTC+ZDV in Côte d'Ivoire. These adults were participating in a trial of early ART and had much higher CD4 counts than those who currently routinely start ART in sub-Saharan Africa. They all received CTX concomitantly with ZDV. We suggest that further early prescriptions of TDF+XTC+ZDV should be carefully monitored and that whenever possible, the rate of early upper digestive adverse events should be compared to that occurring in-patients taking other drug regimens.NCT00495651.

SUBMITTER: Ouattara E

PROVIDER: S-EPMC3643089 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Early upper digestive tract side effects of zidovudine with tenofovir plus emtricitabine in West African adults with high CD4 counts.

Ouattara Eric E Danel Christine C Moh Raoul R Gabillard Delphine D Peytavin Gilles G Konan Romuald R Carrou Jérome Le JL Bohoussou Franck F Eholie Serge P SP Anglaret Xavier X

Journal of the International AIDS Society 20130430

<h4>Introduction</h4>Tenofovir (TDF) with emtricitabine (FTC) and zidovudine (ZDV) is a recognized alternate first-line antiretroviral (ART) regimen for patients who cannot start treatment with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Clinical studies comparing TDF+FTC+ZDV to other regimens are lacking.<h4>Methods</h4>Participants in a trial of early ART in Côte d'Ivoire (Temprano ANRS 12136) started treatment with TDF/FTC plus either efavirenz (EFV) or ZDV (HIV-1+2 dually infec ...[more]

PMID: 23639243

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Project description:As a simplification strategy for treatment-experienced HIV-infected patients who have achieved virologic suppression on a multi-drug, multi-class antiretroviral regimen, the aim of this study was to evaluate the safety, efficacy, and pharmacokinetics of once-daily elvitegravir/cobicistat/emtricitabine/tenofovir disproxil fumarate (E/C/F/TDF) with darunavir.A single arm, open-label 48-week study was conducted of regimen simplification to E/C/F/TDF plus darunavir 800 mg daily from stable therapy including two nucleoside/nucleotide reverse transcriptase inhibitors, a ritonavir-boosted protease inhibitor, and an integrase inhibitor. Participants had plasma HIV viral load consistently < 200 copies/mL for ? 6 months, estimated glomerular filtration rate (eGFR) ? 60 mL/min, and no genotypic resistance to major components of the study regimen. Plasma viral load was measured at weeks 2 and 4, then every 4 weeks throughout the study. Safety laboratory assessments were conducted at baseline and at weeks 12, 24, 36, and 48. Antiretroviral drug concentrations were measured at baseline and once ? 2 weeks after the regimen change.Ten HIV-infected adults (8 male and 2 female; median age 50.5 years) were enrolled. All maintained virologic suppression on the new regimen for 48 weeks. One subject experienced a decrease in eGFR from 62 mL/min at baseline to 52 mL/min at week 12; study medications were continued and his eGFR remained stable (50-59 mL/min) thereafter. No subjects discontinued study medications for renal function changes or other adverse events. Darunavir trough concentration were lower on the new regimen than on darunavir/ritonavir 800/100 mg (n = 5; p < 0.05).Despite low darunavir trough concentrations, treatment simplification to a two-pill, once-daily regimen of E/C/F/TDF plus darunavir was safe and effective for 48 weeks among 10 selected treatment-experienced HIV-infected patients. Trial registration The study protocol was registered with ClinicalTrials.gov (NCT02199613) on July 22, 2014.

Project description:Antiretroviral pre-exposure prophylaxis (PrEP), with daily oral tenofovir disoproxil fumarate or tenofovir disoproxil fumarate in combination with emtricitabine, has been shown to be efficacious for HIV-1 prevention. Although the use of more than one antiretroviral agent is essential for effective HIV-1 treatment, more than one agent might not be required for effective prophylaxis. We assessed the efficacy of single-agent tenofovir disoproxil fumarate relative to combination emtricitabine plus tenofovir disoproxil fumarate as PrEP.We did a randomised, double-blind, placebo-controlled three-group phase 3 trial of daily oral tenofovir disoproxil fumarate and emtricitabine plus tenofovir disoproxil fumarate PrEP in HIV-1 uninfected individuals in heterosexual HIV-1 serodiscordant couples from Kenya and Uganda. After an interim review, the trial's placebo group was discontinued and thereafter the active groups were continued, and participants initially randomly assigned to placebo were offered rerandomisation in a 1:1 ratio to tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate as PrEP. The primary endpoints were HIV-1 seroconversion and safety. This trial is registered with ClinicalTrials.gov, number NCT00557245.4410 (99·6%) of 4427 couples received tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate and were followed up for HIV-1 acquisition. Of 52 incident HIV-1 infections, 31 occurred in individuals assigned tenofovir disoproxil fumarate (incidence 0·71 cases per 100 person-years) and 21 were in those assigned emtricitabine plus tenofovir disoproxil fumarate (0·48 cases per 100 person-years); HIV-1 incidence in the placebo group until discontinuation was two cases per 100 person-years. HIV-1 prevention efficacy with emtricitabine plus tenofovir disoproxil fumarate was not significantly different from that of tenofovir disoproxil fumarate alone (hazard ratio [HR] 0·67, 95% CI 0·39-1·17; p=0·16). Detection of tenofovir in plasma samples, compared with no detection and as measured in seroconverters and a subset of non-seroconverters, was associated with an 85% relative risk reduction in HIV-1 acquisition for the tenofovir disoproxil fumarate group (HR 0·15, 95% CI 0·06-0·37; p<0·0001) and 93% for the emtricitabine plus tenofovir disoproxil fumarate group (0·07, 0·02-0·23; p<0·0001). No significant differences were noted in the frequency of deaths, serious adverse events, or serum creatinine and phosphorus abnormalities between the two groups.These results do not rule out the potential for a slight difference in HIV-1 protection with tenofovir disoproxil fumarate compared with emtricitabine plus tenofovir disoproxil fumarate, but show that once-daily oral tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate regimens both provide high protection against HIV-1 acquisition in heterosexual men and women.Bill & Melinda Gates Foundation and US National Institutes of Health.

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Early upper digestive tract side effects of zidovudine with tenofovir plus emtricitabine in West African adults with high CD4 counts.

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Early upper digestive tract side effects of zidovudine with tenofovir plus emtricitabine in West African adults with high CD4 counts.

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