Dataset Information

Virological efficacy of 24-week fozivudine-based regimen in ART-naive patients from Tanzania and Cote d'Ivoire.

ABSTRACT: Use of zidovudine (ZDV) in antiretroviral therapy is limited by toxicity and twice daily (b.i.d.) dosing. Fozivudine (FZD) is a ZDV prodrug, which is activated intracellularly to ZDV-monophosphate especially in mononuclear cells but not in bone marrow cells. FZD promises improved myelotoxicity and once daily (o.d.) dosing.Randomized clinical trial.We conducted an open-label, phase II, proof-of-concept trial investigating three different FZD doses (800?mg o.d., 600?mg b.i.d., 1200?mg o.d.) versus ZDV (300?mg b.i.d.) in combination with lamivudine and efavirenz in HIV-infected, ART-naive patients from Tanzania and Côte d'Ivoire. The primary objective was to demonstrate virological efficacy after 24 weeks in intent-to treat and per-protocol analysis. Secondary endpoints included safety and pharmacokinetic outcomes.Of 119 participants included in the intent-to treat analysis, HIV RNA less than 50 copies/ml at 24 weeks was observed in 64 of 88 (73%) patients in the combined FZD arms versus 24 of 31 (77%) in the ZDV arm (RR 0.94, 95% confidence interval 0.75-1.18). In the per-protocol analysis, responses were 64 of 77 (87%) versus 23 of 29 (79%), respectively (RR 1.09, 95% confidence interval 0.89-1.34). Outcomes were similar between FZD arms. Overall, treatments were well tolerated. Severe or worse anaemia occurred in two cases (one related to FZD, one to ZDV), grade III/IV neutropenia was less frequent in FZD compared with ZDV arms (22 versus 42%, P?=?0.035). Pharmacokinetic analysis supported o.d. administration of FZD.Virological 24-week efficacy was demonstrated in b.i.d. and o.d. administered FZD-based regimens. Reduced myelotoxicity of FZD needs to be confirmed in a larger trial.

SUBMITTER: Kroidl A

PROVIDER: S-EPMC5278894 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Virological efficacy of 24-week fozivudine-based regimen in ART-naive patients from Tanzania and Côte d'Ivoire.

Kroidl Arne A Ello Frederic F Mgaya Jimson J Lennemann Tessa T Moh Raoul R Maganga Lucas L Eholie Serge S Pruvost Alain A Saathoff Elmar E Girard Pierre-Marie PM Zuhse Ralph R von Massow Friedrich F Anglaret Xavier X Hoelscher Michael M Danel Christine C

AIDS (London, England) 20170201 4

<h4>Objective</h4>Use of zidovudine (ZDV) in antiretroviral therapy is limited by toxicity and twice daily (b.i.d.) dosing. Fozivudine (FZD) is a ZDV prodrug, which is activated intracellularly to ZDV-monophosphate especially in mononuclear cells but not in bone marrow cells. FZD promises improved myelotoxicity and once daily (o.d.) dosing.<h4>Design</h4>Randomized clinical trial.<h4>Methods</h4>We conducted an open-label, phase II, proof-of-concept trial investigating three different FZD doses ...[more]

PMID: 27941394

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Project description:BackgroundEven though the international combat against Neglected Tropical Diseases such as schistosomiasis or soil-transmitted helminthiases depends on reliable therapeutics, anthelminthic pharmacovigilance has been neglected on many national African drug markets. Therefore, quality and composition of Albendazole, Mebendazole and Praziquantel locally collected in Burkina Faso, Côte d'Ivoire, Ghana and Tanzania were analysed.MethodsSamples of 88 different batches were obtained from randomly selected facilities. Sampling took place in Northwest Tanzania, Western Burkina Faso, Southeast Côte d'Ivoire and Southwest Ghana. Visual examination of both packaging and samples was performed according to the WHO 'Be Aware' tool. Products were then screened with the GPHF Minilab, consisting of tests of mass uniformity, disintegration times and thin-layer chromatography (TLC). Confirmatory tests were performed according to international pharmacopoeiae, applying assays for dissolution profiles and high-performance liquid chromatography (HPLC).FindingsDespite minor irregularities, appearance of the products did not hint at falsified medicines. However, 19.6% of the brands collected in Ghana and Tanzania were not officially licensed for sale. Mass uniformity was confirmed in 53 out of 58 brands of tablets. 41 out of 56 products passed disintegration times; 10 out of the 15 failing products did not disintegrate at all. Evaluating TLC results, only 4 out of 83 batches narrowly missed specification limits, 18 batches slightly exceeded them. Not more than 46.3% (31 / 67) of the tablets assayed passed the respective pharmaceutical criteria for dissolution. HPLC findings confirmed TLC results despite shifted specification limits: 10 out of 83 tested batches contained less than 90%, none exceeded 110%.ConclusionIn the four study countries, no falsified anthelminthic medicine was encountered. The active pharmaceutical ingredient was not found to either exceed or fall below specification limits. Galenic characteristics however, especially dissolution profiles, revealed great deficits.

Project description:IntroductionWhether early antiretroviral therapy (ART) initiation could impact sexual risk behaviours remains to be documented. We aimed to investigate changes in sexual behaviours within the 24 months following an early versus standard ART initiation in HIV-positive adults with high CD4 counts.MethodsWe used data from a prospective behavioural study nested in a randomized controlled trial of early ART (Temprano-ANRS12136). Time trends in sexual behaviours from enrolment in the trial (M0) to 12-month (M12) and 24-month (M24) visits were measured and compared, using Generalized Estimating Equations models, between participants randomly assigned either to initiate ART immediately (early ART) or to defer ART initiation until on-going WHO starting criteria are met (standard ART). Indicators of sexual behaviours included 1) sexual activity in the past year, 2) multiple partnership in the past year, 3) unprotected sex at last intercourse and 4) risky sex (i.e. unprotected sex with a partner of HIV negative/unknown status) at last intercourse.ResultsAnalyses included 1952 participants (975 with early ART and 977 with standard ART; overall median baseline CD4 count: 469/mm(3)). Among participants with early ART, significant decreases were found between M0 and M24 in sexual activity (Odds Ratio [OR] 0.72, 95% Confidence Interval [95% CI] 0.57-0.92), multiple partnership (OR 0.57, 95% CI 0.41-0.79), unprotected sex (OR 0.59, 95% CI 0.47-0.75) and risky sex (OR 0.58, 95% CI 0.45-0.76). Among participants with standard ART, sexual behaviours showed similar trends over time. These decreases mostly occurred within the 12 months following enrolment in the trial in both groups and prior to ART initiation in participants with standard ART. For unprotected sex and risky sex, decreases were or tended to be more pronounced among patients reporting that their last sexual partner was non-cohabiting.ConclusionsIn these sub-Saharan adults with high CD4 counts, entry into HIV care, rather than ART initiation, resulted in decreased sexual activity and risky sexual behaviours. We did not observe any evidence of a risk compensation phenomenon associated with early ART initiation. These results illustrate the potential behavioural preventive effect of early entry into care, which goes hand in hand with early ART initiation.

Project description:BACKGROUND:In Côte d'Ivoire, induced abortion is legally restricted unless a pregnancy threatens a woman's life. Yet the limited available evidence suggests abortion is common and that unsafe abortion is contributing to the country's high maternal mortality. Our study aimed to estimate the one-year incidence of induced abortion in Côte d'Ivoire using both direct and indirect methodologies, determine the safety of reported abortions, and identify the women most likely to experience a recent induced abortion or an unsafe abortion. METHODS:In 2018, we conducted a nationally representative, population-based survey of women age 15 to 49 in Côte d'Ivoire. Women reported their own abortion experiences and those of their closest female confidante. We estimated the one-year incidence of induced abortion, and the safety of the abortions women experienced. Using bivariate and multivariate regression, we separately assessed sociodemographic characteristics associated with having had a recent abortion or an unsafe abortion. RESULTS:Overall, 2,738 women participated in the survey, approximately two-thirds of whom reported on the abortion experiences of their closest female friend. Based on respondent data, the one-year incidence of induced abortion was 27.9 (95% CI 18.6-37.1) per 1,000 women of reproductive age, while the confidante incidence was higher at 40.7 (95% CI 33.3-48.1) per 1,000. Among respondents, 62.4% of abortions were most unsafe, while 78.5% of confidante abortions were most unsafe. Adolescents, less educated women, and the poorest women had the most unsafe abortions. CONCLUSION:This study provides the first national estimates of induced abortion incidence and safety in Côte d'Ivoire, using a population-based approach to explore social determinants of abortion and unsafe abortion. Consistent with other research, our results suggest that legal restrictions on abortion in Côte d'Ivoire are not preventing women from having abortions, but rather pushing women to use unsafe, potentially dangerous abortion methods. Efforts to reduce the harms of unsafe abortion are urgently needed.

Dataset Information

Virological efficacy of 24-week fozivudine-based regimen in ART-naive patients from Tanzania and Cote d'Ivoire.

Publications

Virological efficacy of 24-week fozivudine-based regimen in ART-naive patients from Tanzania and Côte d'Ivoire.

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