Mouhamadou Baïla Diallo

Changes in the renal function after tenofovir-containing antiretroviral therapy Initiation in a Senegalese cohort (ANRS 1215)

To describe and compare the changes in renal function between HIV-1 infected adult patients receiving antiretroviral therapy (ART) with and without tenofovir (TDF). The population consisted of 40 patients starting a TDF-containing regimen and 388 patients starting regimen not containing TDF, and followed during 42 months. The estimated glomerular filtration rate (eGFR) was calculated using the Cockroft-Gault and MDRD equations and modeled separately for the first 12 months and the subsequent period. Between baseline and 12 months, the eGFR decreased significantly in patients receiving TDF (-10.40 ml/min), whereas it increased in the other +4.33 ml/min). A significant variability in the eGFR trajectories of patients receiving TDF was observed; 12 (30%) of them experienced a persistent decrease, 5 (12%) had an initial transient increase, and 23 (58%) a steady slow increase in eGFR. The characteristics at baseline of the patients with persistent decrease were not different from the other patients but their immune reconstitution was impaired. After 12 months, patients receiving TDF experienced a higher rate of transition from mild renal impairment (60-90 ml/min/1.73 m(2)) to moderate renal impairment (30-60 ml/min/1.73 m(2)) when compared with patients not receiving TDF. A significant though moderate decline in the renal function was observed in one-third of the patients receiving TDF compared to patients not receiving TDF. Moreover, this impairment was persistent after the first year of treatment.

Tenofovir-Emtricitabine-Efavirenz in HIV-I-Infected Adults in Senegal: A 96-Week Pilot Trial in Treatment-Naive Patients

We report the results of a pilot open-label trial of a tenofovir (TDF)/emtricitabine (FTC)/efavirenz (EFV) combination conducted in Dakar, Senegal. Forty HIV-1-infected patients, naive of antiretroviral treatment and without active opportunistic disease, were included and followed through 96 weeks. At weeks 48 and 96, respectively, 82.5% and 85% of patients had HIV-1 RNA <400 copies/mL (72.5% and 77.5% with HIV-1 RNA <50 copies/mL). Between baseline and week 96, the mean (SD) CD4 count increased from 126 (102) to 338 (155) cells/mm3. The mean (SD) creatinine clearance decreased from 92 (36) to 73 (19) mL/min (P = .001). Treatment adherence was at least 94% at all scheduled visits. The efficacy and tolerability of a TDF/FTC/EFV combination were high and similar to those observed in Northern countries. This drug combination can be recommended in limited-resource countries, as did the World Health Organization (WHO) and should be made readily available as a fixed-dose combination.

High Prevalence of Severe Food Insecurity and Malnutrition among HIV-Infected Adults in Senegal, West Africa

Background Malnutrition and food insecurity are associated with increased mortality and poor clinical outcomes among people living with HIV/AIDS; however, the prevalence of malnutrition and food insecurity among people living with HIV/AIDS in Senegal, West Africa is unknown. The objective of this study was to determine the prevalence and severity of food insecurity and malnutrition among HIV-infected adults in Senegal, and to identify associations between food insecurity, malnutrition, and HIV outcomes. Methods We conducted a cross-sectional study at outpatient clinics in Dakar and Ziguinchor, Senegal. Data were collected using participant interviews, anthropometry, the Household Food Insecurity Access Scale, the Individual Dietary Diversity Scale, and chart review. Results One hundred and nine HIV-1 and/or HIV-2 participants were enrolled. The prevalence of food insecurity was 84.6% in Dakar and 89.5% in Ziguinchor. The prevalence of severe food insecurity was 59.6% in Dakar and 75.4% in Ziguinchor. The prevalence of malnutrition (BMI <18.5) was 19.2% in Dakar and 26.3% in Ziguinchor. Severe food insecurity was associated with missing clinic appointments (p = 0.01) and not taking antiretroviral therapy due to hunger (p = 0.02). Malnutrition was associated with lower CD4 cell counts (p = 0.01). Conclusions Severe food insecurity and malnutrition are highly prevalent among HIV-infected adults in both Dakar and Ziguinchor, and are associated with poor HIV outcomes. Our findings warrant further studies to determine the root causes of malnutrition and food insecurity in Senegal, and the short- and long-term impacts of malnutrition and food insecurity on HIV care. Urgent interventions are needed to address the unacceptably high rates of malnutrition and food insecurity in this population.

Tenofovir plasma concentrations related to estimated glomerular filtration rate changes in first-line regimens in African HIV-infected patients: ANRS 12115 DAYANA substudy

OBJECTIVES An open-label randomized trial (DAYANA) was conducted in sub-Saharan settings to evaluate four different regimens containing tenofovir disoproxil fumarate as first-line treatment for HIV infection. The objectives of the present substudy were to assess the relationship between trough concentrations of tenofovir in plasma collected after 24 h (C24) and estimated glomerular filtration rates (eGFR) calculated by the different formulae that are available. METHODS The criteria for eligibility were those of the DAYANA trial, recruiting naive patients. The four tenofovir regimens were: Group 1, tenofovir/emtricitabine/nevirapine; Group 2, tenofovir/lopinavir/ritonavir; Group 3, tenofovir/emtricitabine/zidovudine; and Group 4, tenofovir/emtricitabine/efavirenz. The C24 of tenofovir was determined using LC-MS/MS. The eGFR was calculated using the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae. RESULTS The median C24 of tenofovir was 42 ng/mL. The C24 of tenofovir was higher with lopinavir/ritonavir than with the other three regimens: at Week 4, 84 ng/mL versus 25 ng/mL; and at Week 48, 81 ng/mL versus 52 ng/mL. The baseline merged eGFR was 98.2 mL/min/1.73 m(2) with the CKD-EPI equation. Only the mean changes in eGFR in Group 2 differed from the absolute value of zero (-8.2 mL/min/1.73 m(2)) with the CKD-EPI equation between baseline and Week 48. The Cockcroft-Gault formula is inappropriate for these African patients because it underestimated the baseline eGFR and overestimated the changes in eGFR between baseline and Week 48. CONCLUSIONS In this population of mostly female HIV-1-infected African patients, tenofovir plasma overexposure was associated with PI/ritonavir and a time-dependent decrease in eGFR, probably via an inhibition of MRP2/MRP4 efflux transporters. The close monitoring over time of the eGFR using MDRD or CKD-EPI calculations and by using other biomarkers of renal disorder should be proposed as an alternative to therapeutic drug monitoring in resource-limited countries.

Prevention and Care of Hepatitis B in Senegal; Awareness and Attitudes of Medical Practitioners.

In highly endemic settings for hepatitis B virus (HBV) infection such as Senegal, access to HBV prevention and care is rapidly evolving. In this context, all medical practitioners should have baseline knowledge on HBV infection and promote access to vaccination, screening, and care. A knowledge and attitudes survey on HBV infection was conducted among a randomly selected sample of medical practitioners in Senegal. Participants were asked to fill-out a questionnaire on the HBV epidemiology, prevention, and treatment. A 60-item knowledge score was computed; the lower quartile of the observed score was used to define poor knowledge. Factors associated with poor knowledge were assessed using a logistic regression model. A total of 127 medical practitioners completed the questionnaire. Only 14 (11.0%) participants knew that HBV vaccine could be safely administered to pregnant women and 65 (51.2%) to newborns. Older practitioners (> 40 years) as well as general practitioners (compared with specialists) were more likely to have a poor knowledge score with odds ratios (ORs) of 3.1 (95% confidence interval [CI] 1.0-9.2) and 2.6 (95% CI 1.0-7.3), respectively. Practitioners who declared not to recommend HBV screening frequently during their consultation were more likely to present a poor knowledge score [OR: 3.0; (95% CI 1.1-8.2)]. As universal HBV screening is being promoted in countries with endemic HBV infection, our finding that poor screening attitudes were associated with a poor knowledge is of concern. There is a need to raise awareness of medical practitioners in Senegal toward universal HBV screening and early vaccination of newborns.

The dimensions of food insecurity and malnutrition among people living with HIV in Senegal, West Africa

ABSTRACT An understanding of the factors contributing to food insecurity and malnutrition among people living with HIV (PLHIV) in Senegal is urgently needed in order to develop effective interventions. The goals of this study were to identify differences in the dimensions of food security among PLHIV in Dakar versus Ziguinchor, Senegal, to determine which of these dimensions are most predictive of severe food insecurity, and to identify factors associated with malnutrition. We conducted a cross-sectional study at outpatient clinics in Dakar and Ziguinchor, Senegal. Data were collected using participant interviews, anthropometry, the Household Food Insecurity Access Scale, the Individual Dietary Diversity Scale, and chart review. Interviews were conducted with ninety-five food insecure, HIV-infected subjects. Daily household income and daily food expenditure per household member were the strongest predictors of severe food insecurity. The practice of agriculture, livestock ownership, nutritional status, and HIV outcomes were not predictive of severe food insecurity. CD4 count <350/mm3 was the strongest predictor of malnutrition. Severe food insecurity, daily household income, daily food expenditure per household member, dietary diversity score, skipping meals, the practice of agriculture, livestock ownership, ART status, and adherence were not predictive of malnutrition. This is the first study to analyze the dimensions of food security among PLHIV in Senegal. We discovered important differences in food access, availability, stability, and utilization in Dakar versus Ziguinchor. We found that economic access was the strongest predictor of severe food insecurity and poorly controlled HIV was the strongest predictor of malnutrition. Our findings suggest that the interventions needed to address food insecurity differ from those necessary to target malnutrition, and that effective interventions may differ in Dakar versus Ziguinchor. Furthermore, this study highlights a need for a greater understanding of the relationship between HIV and malnutrition among individuals receiving ART in resource-limited settings.

Efficacy and Safety of Unboosted Atazanavir in Combination with Lamivudine and Didanosine in Naive HIV Type 1 Patients in Senegal

The use of ritonavir as a protease inhibitor boost is rare in sub-Saharan Africa because a heat-stable formula is not available. We report the results of an open-label pilot trial with unboosted atazanavir in combination with lamivudine and didanosine as first-line therapy conducted in Senegal. Treatment-naive HIV-1 infected adult patients without active opportunistic disease were included. The primary endpoint was the proportion of patients with plasma HIV-1 RNA <400 copies/ml at week 48. Forty patients (12 men and 28 women; mean age +/- SD: 40 +/- 9 years) were included. Treatment was changed during the study for two patients (pregnancy, tuberculosis); one patient was lost to follow-up and one patient died (gastroenteritis with cachexia). At week 48, 78% [95% confidence interval (CI): 65-90%] and 68% (95% CI: 53-82%) of the patients had HIV-1 RNA <400 and <50 copies/ml, respectively (intent-to-treat analysis; not completer = failure). Among the seven patients with HIV-1 RNA >or=400 copies/ml at week 48, five were not compliant; genotyping analysis (n = 4) did not reveal a major mutation for protease inhibitors. The mean CD4 cell count change from baseline to week 48 was +238 +/- 79 cells/mm(3). The combination of unboosted atazanavir with lamivudine and didanosine was efficient and well tolerated in HIV-1-infected patients with results similar to those observed in Northern countries. These results suggest that unboosted atazanavir with its high genetic barrier could be a valuable alternative to NNRTIs in resource-limited countries in some HIV-1-infected patients in case of compliance issues with NNRTIs, intolerance to NNRTIs, resistance mutations to NNRTIs, in women with childbearing potential, or as a maintenance therapy in patients with virological suppression.