Solthis

Paris, France
Paris, France
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Charpentier C.,University Paris Diderot | Bellecave P.,Bordeaux University Hospital Center | Cisse M.,Service de Dermatologie | Mamadou S.,Laboratoire Of Microbiologie | And 16 more authors.
Antiviral Therapy | Year: 2011

Background: The aim of the study was to assess the prevalence of antiretroviral drug resistance mutations in HIV-1 from recently diagnosed and untreated patients living in Conakry, Guinea-Conakry and in Niamey, Niger. Methods: The study was performed in two countries of Western Africa - Guinea-Conakry and Niger - using the same survey method in both sites. All newly HIV-1 diagnosed patients, naive of antiretroviral drugs, were consecutively included during September 2009 in each of the two sites. Protease and reverse transcriptase sequencing was performed using the ANRS procedures. Drug resistance mutations were identified according to the 2009 update surveillance drug resistance mutations. Results: In Conakry, 99 patients were included, most of whom (89%) were infected with CRF02-AG recombinant virus. Resistance analysis among the 93 samples showed that ≥1 drug resistance mutation was observed in 8 samples, leading to a prevalence of primary resistance of 8.6% (95% CI 2.91-14.29%). In Niamey, 96 patients were included; a high diversity in HIV-1 subtypes was observed with 47 (51%) patients infected with CRF02-AG. Resistance analysis performed among the 92 samples with successful genotypic resistance test showed that ≥1 drug resistance mutation was observed in 6 samples, leading to a prevalence of primary resistance of 6.5% (95% CI 1.50-11.50%). Conclusions: We reported the first antiretroviral drug resistance survey studies in antiretroviral-naive patients living in Guinea-Conakry and in Niger. The prevalence of resistance was between 6% and 9% in both sites, which is higher than most of the other countries from Western Africa region. ©2011 International Medical Press.


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.


Landier J.,Institute Pasteur Paris | Akonde A.,Solthis | Pizzocolo C.,Solthis | Haidara I.,Hopital Regional de Segou | And 5 more authors.
AIDS Care - Psychological and Socio-Medical Aspects of AIDS/HIV | Year: 2011

In sub-Saharan Africa, while antiretroviral therapy (ART) becomes widely available, access to biological measurements to monitor patients under ART remains scarce, making the management of ART difficult. We described the management of switching to second-line ART where HIV care is provided mainly in secondary health-care structures, in the region of Segou, Mali. Of 865 patients, followed under ART for a median time of 15 months, 40 switched to second-line ART (3.3 switches/100 person years). Reason for switching was failure in 18 patients (after 21 months in median) and severe intolerance in 13 (after three months in median). Switching to second-line ART occurred earlier when motivated by intolerance than by failure. The low rate of switch compares well with other studies, but was low compared to the expected rate of failure, and may indicate that physicians are reluctant to switch ART when treatment options are limited. © 2011 Taylor & Francis.


PubMed | SOLTHIS, Institute Pasteur Paris and University of Geneva
Type: Journal Article | Journal: PloS one | Year: 2013

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.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.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 second-line ART.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.


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.


PubMed | Solthis, Ministere de la Sante publique du Niger and Coordination intersectorielle de lutte contre les IST VIH sida de Niamey
Type: Journal Article | Journal: Bulletin de la Societe de pathologie exotique (1990) | Year: 2016

In Niger, the tuberculosis (TB) screening among people living with human immunodeficiency virus (HIV) (PLHIV) is nonsystematic and the use of additional tests is very often limited. The objective of this research is to evaluate the performance and the cost-effectiveness of various paraclinical testing strategies of TB among adult patients with HIV, using available tests in routine for patients cared in Niamey. This is a multicentric prospective intervention study performed in Niamey between 2010 and 2013. TB screening has been sought in newly diagnosed PLHIV, before ART treatment, performing consistently: a sputum examination by MZN (Ziehl-Nielsen staining) and microscopy fluorescence (MIF), chest radiography (CR), and abdominal ultrasound. The performance of these different tests was calculated using sputum culture as a gold standard. The various examinations were then combined in different algorithms. The cost-effectiveness of different algorithms was assessed by calculating the money needed to prevent a patient, put on ART, dying of TB. Between November 2010 and November 2012, 509 PLHIV were included. TB was diagnosed in 78 patients (15.3%), including 35 pulmonary forms, 24 ganglion, and 19 multifocal. The sensitivity of the evaluated algorithms varied between 0.35 and 0.85. The specificity ranged from 0.85 to 0.97. The most costeffective algorithm was the one involving MIF and CR. We recommend implementing a systematic and free direct examination of sputum by MIF and a CR for the detection of TB among newly diagnosed PLHIV in Niger.


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.


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.


Germanaud D.,SOLTHIS | Derache A.,SOLTHIS | Traore M.,SOLTHIS | Madec Y.,SOLTHIS | And 6 more authors.
The Journal of antimicrobial chemotherapy | Year: 2010

OBJECTIVES: To evaluate the virological response and to describe the resistance profiles in the case of failure after 6 months of first-line highly active antiretroviral therapy (HAART) in HIV-1-infected children living in resource-limited settings. PATIENTS AND METHODS: Ninety-seven HIV-1-infected children who started two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) (mainly zidovudine/lamivudine/nevirapine) in Mali were prospectively studied. Virological failure (VF) was defined as loss to follow-up, death or HIV-1 RNA viral load (VL) of >400 copies/mL at 6 months. When VL was >50 copies/mL, a genotypic resistance test was performed. RESULTS: Among the 97 children, median age at antiretroviral initiation was 31 months and the majority were in WHO clinical (77.3%) and immunological (70.1%) stage III or IV. At month 6, 44% of children had VL > 400 copies/mL (61% VF). Among the children with detectable VL, 30/37 genotypic resistance tests were available, 8 with wild-type viruses and 22 with resistance mutations (73%): 19 M184V/I, 21 NNRTI mutations and only 3 thymidine analogue mutations (TAMs) (K70R, D67N and L210W in three distinct viruses). At failure, 6/8 children with wild-type viruses had a VL of <1000 copies/mL whereas 21/22 with resistant viruses had a VL of >1000 copies/mL. CONCLUSIONS: Under NNRTI-based regimens, early detection of VF could allow the reinforcement of adherence when VL was <1000 copies/mL, because in most of these cases no resistance mutations were detected, or a change to a protease inhibitor-based regimen if VL was >1000 copies/mL. The low frequency of TAMs suggests that most NRTIs can be used in a second-line regimen after early failure.


PubMed | Solthis, Hopital Bichat Claude Bernard laboratoire pharmaco toxicologie, France Expertise Internationale and Hopital Foch
Type: Clinical Trial | Journal: Bulletin de la Societe de pathologie exotique (1990) | Year: 2016

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.

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