P.S. Sow

Long-term benefits of highly active antiretroviral therapy in Senegalese HIV-1-infected adults.

Objectives: To assess the long-term survival, as well as the immunologic and virologic effectiveness, adherence, and drug resistance, in HIV-infected patients receiving highly active antiretroviral therapy (HAART) in one of the oldest and best-documented African cohorts. Methods: A prospective observational cohort study included the first 176 HIV-1-infected adults followed in the Senegalese government-sponsored antiretroviral therapy initiative launched in August 1998. Patients were followed for a median of 30 months (interquartile range, 21-36 months). HAART comprised 2 nucleoside reverse transcriptase inhibitors and either 1 protease inhibitor or 1 nonnucleoside reverse transcriptase inhibitor. Results: At baseline, 92% of patients were antiretroviral naive and 82% had AIDS; the median CD4 count was 144 cells/mm3, and median viral load was 202,368 copies/mL. The survival probability was high (0.81 at 3 years; 95% CI, 0.74-0.86) and was independently related to a baseline hemoglobin level <10 g/dL and a Karnofsky score <90%. Antiviral efficacy was consistently observed during the 3 years of treatment (−2.5 to −3.0 log10 copies/mL; 60-80% of patients with viral load <500 copies/mL) and the CD4 count increase reached a median of 225 cells/mm3. Most patients reported good adherence (80-90%). The emergence of drug resistance was relatively rare (12.5%). Conclusion: This study shows that clinical and biologic results similar to those seen in Western countries can be achieved and sustained during the long term in Africa.

Quality of life and depression among HIV-infected patients receiving efavirenz- or protease inhibitor-based therapy in Senegal.

Efavirenz has been associated with neuropsychiatric disorders, but little is known about depression and quality of life in sub‐Saharan Africa, where nonnucleoside reverse transcriptase inhibitor (NNRTI)‐based regimens are still the first‐line treatment recommended by the World Heath Organization (WHO) and are widely prescribed.

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.

Profil actuel des patients infectés par le VIH hospitalisés à Dakar (Sénégal)

Ten years after the introduction of the Senegalese Antiretroviral Drug Access Initiative in 1998, we conducted a retrospective study of the epidemiological and clinical profiles and outcome of HIV-infected patients hospitalized in the Infectious Diseases Clinic of Fann Teaching Hospital in Dakar between 2007 and 2008. During these 2 years, 527 HIV-positive patients were included. The average age of the patients was 41 ± 10 years, and the sex-ratio (F/M) was 1.1; 56% of patients were married. The average interval before admission was 40 ± 57 days. Fever (83%), loss of weight (83%) and cough (54%) were the principal symptoms. Tuberculosis (40.9%) and gastrointestinal candidiasis (38.9%) were the commonest opportunistic infections. Most patients were diagnosed at the AIDS stage (88%) and the CD4+ T lymphocyte count was ≤ 200/mm3 in 86% of cases. Hospital fatality was 44% (231/527). Tuberculosis (36%), bacterial pneumonia (18%) and encephalitis (12%) were the most frequent causes of death. Despite the availability of and free access to antiretroviral drugs in Senegal, the mortality associated with HIV infection remains very high due to late diagnosis. The population must be educated to boost early screening and care.

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.

Immune reconstitution syndrome in the course of antiretroviral treatment in Senegal

L’introduction d’associations de médicaments antirétroviaux a profondément modifié l’histoire naturelle de l’infection VIH. Mais depuis un certain temps, avec l’augmentation du ombre de personnes traitées, il a été constaté la réapparition aradoxale de pathologies opportunistes, dans le cadre du synrome inflammatoire de reconstitution immunitaire (IRIS). Notre présent travail constitue notre contribution à l’étude e l’IRIS notamment dans les pays à ressources limitées : le énégal. Il s’agissait d’analyser les particularités des aspects pidémiologiques, cliniques et immunovirologiques de la surenue d’infections opportunistes chez des patients vivant avec e VIH sous traitement antirétroviral (ARV) dans le cadre du yndrome IRIS.

H-03 Aspects épidémio-cliniques et psychosociaux au cours du sida à Dakar : étude préliminaire prospective

Introduction et objectifs Decrire les aspects epidemio-cliniques et psychosociaux au cours du sida a Dakar. Materiels et methodes Etude prospective realisee chez les patients VIH positif hospitalises au service des maladies infectieuses Ibrahima DIOP Mar du CHU de Fann du 1 er janvier 2008 au 31 mars 2008. Resultats Ont ete inclus 65 patients dont l’âge moyen etait de 38 ans ± 8,13 ans. Le sex-ratio etait de 1, 2 et 34 % des patients etaient sans profession. Dans 92 % des cas, les patients n’avaient pas informe leur conjoint de leur statut serologique. Ils etaient accompagnes durant leur hospitalisation par le conjoint ou un membre de la famille au premier degre dans 95 % des cas. Le delai moyen de consultation etait de 109 ± 80 jours et a l’annonce de la serologie, les patients ont surtout exprime un sentiment de mort imminente (55 % des cas) et de punition divine (35 % des cas). Les principales affections opportunistes etaient la candidose buccale (40 % des cas), la tuberculose pulmonaire (30 % des cas) et la diarrhee chronique (37 % des cas). Un ou plusieurs examens complementaires n’ont pas pu etre effectues chez 30 % des patients. Le taux moyen de lymphocytes T CD4 etait de 110 ± 80 /mm 3 . Le cout moyen de l’hospitalisation par patient a ete estime a 65 000 francs CFA ± 45 000 Francs CFA. (99 € ± 69 €). Une letalite globale de 26 % a ete notee. Conclusion La prise en charge mutidisciplinaire multidisciplinaire des sujets infectes par le VIH devrait etre renforcee dans toutes ses composantes surtout psycho-sociales et economiques.

Profil actuel de la toxoplasmose cérébrale en milieu hospitalier à Dakar

OBJECTIVE To describe the current epidemiologic, clinical, diagnostic, and prognostic characteristics of cerebral toxoplasmosis in a hospital setting in Dakar. METHODS This descriptive and analytic study examined the records of all HIV-positive patients with cerebral toxoplasmosis hospitalized at the infectious disease department at Fann (teaching) Hospital from January 2007 through December 2010. The diagnosis was based on clinical and computed tomography criteria completed by a therapeutic test with Cotrimoxazole. RESULTS There were 26 cases of cerebral toxoplasmosis during the study period. The sex ratio (F/M) was 1.4. The mean age was 41.5 ± 11.2 years. The clinical signs were predominantly fever (88.5%), headache (77.5%), focal signs (64.5%), and disorders of consciousness (61.5%). Brain lesions were most often multiple (64.3%), with mass effects (54.1%) and peripheral edema (77.8%). Seven of the 26 patients died (lethality rate: 29.1%). Impaired consciousness (p = 0.023), high CD8 T-cell counts (p = 0.009), and anemia (p = 0.003) were significantly associated with a higher mortality rate. CONCLUSION Cerebral toxoplasmosis remains a complication of AIDS in Dakar. Anemia, impaired consciousness, and high CD8(+) T cell counts were factors indicative of poor prognosis.

Évaluation de la tolérance de l'association zidovudine-lamivudine-névirapine chez les patients VIH-1 au Centre hospitalier de Fann à Dakar Evaluation of tolerance of zidovudine-lamivudine-nevirapine combination in HIV 1 patients in Fann Teaching Hospital in Dakar

We conducted a study to evaluate the tolerance of the zidovudine (AZT), lamivudine (3TC) and nevirapine (NVP) combination regimen in HIV-1 patients by a descriptive analytical retrospective study of all HIV-1 patients receiving AZT-3TC-NVP combination between 2008 and 2011. Seventy patients were included. Two thirds of the patients presented at least one side effect (44 cases). The digestive disorders (15 cases) and neuropsychiatric (14 cases) were the most frequent. Epigastralgia (20%), headaches (20%) and arthralgias (13%) were main side effects. A maculo-papular exanthema was noted in three cases. During the follow-up, five patients presented with anemia. No patient presented hepatic cytolysis due to NVP. All the patients followed for more than six months presented a side effect against 29.7% when the duration of treatment was equal to or less than 6 months (p=10(-5)). Most of the side effects due to the association AZT/3TC/NVP are minor. The evaluation of the clinical and biological tolerance must be maintained during all the follow-up.

[Efficacy and tolerance of tenofovir-lamivudine-efavirenz combination in HIV-1 patients in Fann Teaching Hospital in Dakar].

We conducted a study to evaluate the efficacy and tolerance of the tenofovir (TDF), lamivudine (3TC) and efavirenz (EFV) combination regimen in HIV-1 patients by a descriptive analytical retrospective study of all HIV-1 patients receiving TDF-3TC-EFV combination between 2007 and 2011. Collected data was analysed using EpiInfo™ version 6.04. One hundred patients were included, with an average follow-up duration of 27 months and 19 days (± 21 months and 14 days).We observed an average increase in body weight of about 8 kg per annum, with an average rise in CD4 count of 100/mm(3) by the end of the second year. A reduction in viral load with 71% of patients in therapeutic success at 24 month of treatment was noted. Ninety-two patients presented with at least one side effect, mostly being Grade 1 or 2 (96.36%). Neurological (24 patients) and digestive (20 patients) complaints comprised the commonest reported side effects. Four patients had adverse effects severe enough to warrant a change in treatment regimen, principally due to renal insufficiency. Thirteen subjects died. Patients receiving TDF-3TC-EVF combination therapy need rigorous surveillance because this combination, although efficient, is not without significant adverse effects.