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Le Touquet – Paris-Plage, France

Camara S.,HOpital Foch | Zucman D.,HOpital Foch | Vasse M.,HOpital Foch | Goudjo A.,France Expertise Internationale | And 2 more authors.
Bulletin de la Societe de Pathologie Exotique | Year: 2014

Although second-line generic antiretroviral drugs are of great value in developing countries there are concerns regarding their quality and safety. This study is a case report and pharmacological study in healthy volunteers. A French subject of sub-saharan origin who visited Republic of Congo received a post-exposure treatment with AZT+3TC and LPV/r (200/50 mg, Arga-L®, India) following unprotected sexual intercourse. Two days later, in France, tests showed that plasma concentrations of lopinavir and ritonavir were undetectable. The WHO prequalification list showed Arga-L® was not prequalified. A pharmacological study in healthy volunteers evaluated oral bioavailability: plasma concentrations of generic LPV/r Arga-L® and LPV/r Kaletra® (400/100 mg) were measured after one single dose at 7 days apart in four healthy volunteers. Concentrations of Arga-L® at 12 h after intake were considerably lower than those of Kaletra®, revealing very low oral bioavailability of generic lopinavir and ritonavir (<10%) compared to the brand-name drug. We found that Arga-L®, despite having adequate qualitative and quantitative drug contents, had very poor bio availability compared to Kaletra®. In order to avoid the selection and the spread of drug-resistant HIV strains, rigorous pharmacological monitoring of generic antiretroviral drugs that are not pre-qualified by WHO, but are marketed in Africa, must be a priority for health authorities. © 2014, Springer-Verlag France.

Maiga A.I.,University Pierre and Marie Curie | Maiga A.I.,University of Bamako | Descamps D.,University Paris Diderot | Morand-Joubert L.,University Pierre and Marie Curie | And 14 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2010

Susceptibility to etravirine (ETR), an expanded-spectrum nonnucleoside reverse transcriptase inhibitor (NNRTI), is dependent on the type and number of NNRTI resistance-associated mutations (RAMs). Studies have shown that some HIV-1 subtypes may have natural polymorphisms described as ETR RAMs. This study addresses the prevalence of ETR RAMs in treatment-naïve patients infected with HIV-1 non-B subtypes and its potential impact on ETR susceptibility. The prevalence of ETR RAMs in 726 antiretroviral-naïve patients infected with non-B HIV-1 subtypes was studied. ETR genotypic resistance was interpreted according to Agence Nationale de Recherches sur le SIDA and Stanford algorithms. NNRTI phenotypic susceptibilities of samples with at least one ETR RAM were measured. Overall, 75 (10.3%) of 726 sequences harbored at least one ETR RAM: sequences from 72 patients (10%) each had one ETR RAM, and sequences from 3 patients (0.4%) each had two ETR RAMs (V90I and Y181C in one case and V90I and A98G in two cases). None of the viruses had three or more ETR RAMs, and none were consequently classified as resistant to ETR. All sequences with two ETR RAMs belonged to subtype CRF02-AG. The presence of one ETR RAM was statistically more frequent in subtype CRF02-AG than in other non-B subtypes (P = 0.004). Three new mutation profiles (E138A and V179I, Y181C and H221Y, and V90I and Y181C) showing decreased ETR phenotypic susceptibility were identified. In conclusion, although the prevalence of ETR RAMs in treatment-naïve patients infected with non-B HIV-1 subtypes was 10%, in most cases this had no significant impact on ETR susceptibility. However, the transmission of drug-resistant viruses with Y181C in a non-B genetic background has a potential for impact on ETR susceptibility. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Madec Y.,Institute Pasteur Paris | Leroy S.,Institute Pasteur Paris | Rey-Cuille M.-A.,Institute Pasteur Paris | Huber F.,Solthis | Calmy A.,University of Geneva
PLoS ONE | Year: 2013

Objectives: Switching to second-line antiretroviral therapy (ART) largely depends on careful clinical assessment and access to biological measurements. We performed a systematic review and meta-analysis to estimate the incidence of switching to second-line ART in sub-Saharan Africa and its main programmatic determinants. Methods: We searched 2 databases for studies reporting the incidence rate of switching to second-line ART in adults living in sub-Saharan Africa. Data on the incidence rate of switching were pooled, and random-effect models were used to evaluate the effect of factors measured at the programme level on this incidence rate. Results: Nine studies (157,340 patients) in 21 countries were included in the meta-analysis. All studies considered patients under first-line ART and conditions to initiate ART were similar across studies. Overall, 3,736 (2.4%) patients switched to second-line ART. Incidence rate of switch was in mean 2.65 per 100 person-years (PY) (95% confidence interval: 2.01-3.30); it ranged from 0.42 to 4.88 per 100 PY and from 0 to 4.80 per 100 PY in programmes with and without viral load monitoring, respectively. No factors measured at the programme level were associated with the incidence rate of switching to secondline ART. Conclusion: The low incidence rate of switching to second-line ART suggests that the monitoring of patients under ART is challenging and that access to second-line ART is ineffective; efforts should be made to increase access to second-line ART to those in need by providing monitoring tools, education and training, as well as a more convenient regimen. © 2013 Madec et al.

Kelly J.D.,Baylor College of Medicine | Hubenthal E.A.,Baylor College of Medicine | Lurton G.,Solthis | Empson S.F.,University of California at San Francisco | And 4 more authors.
International Journal of STD and AIDS | Year: 2013

In resource-poor settings, studies validating multiple self-report measures of adherence are limited and do not include data from West Africa. We prospectively assessed the associations between multiple self-report measures of adherence in 58 patients receiving antiretroviral therapy. Self-report measures included a 30-day visual analog scale, 30-day qualitative single-item measure, Adult AIDS Clinical Trial Group 4-day recall, and 3-level categorical 7-day qualitative measure. Unannounced pill count was the objective measure. Spearman's rho correlation coefficients, Bland-Altman plots, and receiver operator curve analyses were performed. Median and mean adherence by pill count were 81.8% and 78.6%, respectively. All self-report measures had either intermediate or high correlation with the pill count, and the 7-day measure had the highest level of correlation with pill count (r = 0.72). All self-report measures demonstrated good agreement when mean pill count adherence was greater than 90%. All but the 7-day measure posed challenges to patient understanding and administration of the measure. In this sample of participants that displayed largely suboptimal adherence, the 7-day measure was preferable, but all self-report measures demonstrated relatively good agreement with the objective criterion pill count measure and are adequate for clinical use in settings such as Sierra Leone. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Madec Y.,Institute Pasteur Paris | Germanaud D.,Solthis | Moya-Alvarez V.,Solthis | Alkassoum W.,Service de pediatrie | And 7 more authors.
PLoS ONE | Year: 2011

Background: In developing countries, malnutrition is a contributing factor in over 50% of child deaths. Mortality rates are higher in underweight children, and HIV-infection is known to increase underweight. Our goals were to evaluate the prevalence of HIV among children hospitalised for severe malnutrition (SM) at the Niamey national hospital (Niger), and to compare renutrition and mortality by HIV-status. Methods: Retrospective study based on all children <5 years hospitalised for SM between January 1st 2008 and July 1st 2009. HIV-prevalence was the ratio of HIV+ children on the number of children tested. Duration of renutrition and mortality were described using survival curves. Results: During the study period, 477 children were hospitalised for SM. HIV testing was accepted in 470 (98.5%), of which 40 were HIV+ (HIV prevalence (95% confidence interval) of 8.6% (6.2-11.5)). Duration of renutrition was longer in HIV+ than HIV- children (mean: 22 vs. 15 days; p = 0.003). During renutrition, 8 (20%) and 61 (14%) HIV+ and HIV- children died, respectively (p = 0.81). Conclusion: Around 9% of children hospitalised for severe malnutrition were HIV infected, while in Niger HIV prevalence in adults is estimated at 0.8%. This pleads for wider access to HIV testing in this population. © 2011 Madec et al.

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