ART initiation in an outpatient treatment center in Dakar, Senegal: A retrospective cohort analysis (1998-2015).

OBJECTIVE: To examine how patient characteristics combined with ART eligibility expansions affect the initiation of antiretroviral therapy (ART) among eligible patients attending a referral center in Senegal from 1998 to 2015. METHODS: This is a retrospective observational study carried out at the outpatient treatment Centre (Centre de Traitement Ambulatoire) in Dakar, Senegal, based on computerized medical records, gathered from 1998 to 2015, of ART-naïve patients over 15 years of age. ART eligibility was defined as (CD4 count below 200) or as (WHO stage 4) or as (WHO stage 3 with (CD4 count below 350 or with unavailable CD4 count)) in 1998-2010; as (CD4 count below 350) or as (WHO stage 3 or 4) in 2011-2013; as (CD4 count below 500) or as (WHO stage 3 or 4) in 2014-2015. Four periods were defined according to ART eligibility expansions and Senegal's HIV care history: 1998-2003 (P 1), 2004-2010 (P 2), 2011-2013 (P3), and 2014-2015 (P4). Patients were expected to participate financially in their treatment during the first period (P1). RESULTS: A total of 3651 patient records were included. The median patient age was 40 years (IQR: 32-48). Women represented 56% of the population. The median CD4 count was 183 cells/mm3. Overall, 53% of patients had CD4 < 200 cells/mm3 at entry. This proportion reached 45% in 2014-2015. 2535 patients (69%) were eligible for therapy, including 1503 (41%) who started ART. The proportion of treated patients among those who were eligible at entry or later increased steadily from 25%, 47%, 75% to 82% in the four periods, respectively. The median time to treatment decreased from 5.6 months (IQR: 3-11) in P1 to 0.8 months (IQR: 0-2) in P4. Eligible patients with more advanced disease (CD4<200 cells/mm3 and/or clinical stage 3 or 4) were more likely to be ART initiated than those with CD4≥200 cells/mm3 and/or clinical stage 1 or 2 at each stage of ART eligibility expansion. CONCLUSION: ART eligibility expansions were marked by a sharp increase in the proportion of eligible patients initiating treatment. These results show that in terms of management, the target of "Test and Treat" can be easily reached but that HIV testing will remain a key element to improve treatment success, as illustrated by the high proportion of people with advanced stage of infection at the time of ART initiation.

Low rate of genotypic HIV-1 drug-resistant strains in the Senegalese government initiative of access to antiretroviral therapy.

OBJECTIVE: To monitor the prevalence of antiretroviral (ARV)-resistant HIV-1 viruses, and the genotypic mutations in patients enrolled in the Senegalese initiative for access to antiretroviral treatment (ART). METHODS: A total of 80 patients with a virological follow-up of at least 6 months were selected, 68 were ART-naive and 12 ART-experienced. Genotypic resistance to ARV was studied at baseline for a random subset of patients and at each rebound in plasma viral load during ART, by sequencing the protease and reverse transcriptase genes. RESULTS: At baseline, 66 patients received highly active antiretroviral therapy (HAART) [2 nucleoside reverse transcriptase inhibitors (NRTIs) +1 protease inhibitor (PI) (n = 64) or 2 NRTIs + 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) (n = 2)] and 14 patients (17.5%) started with a dual therapy because of ongoing antitubercular therapy or efficient previous bitherapy for the ART-experienced patients. The emergence of drug-resistant viruses (n = 13) during follow-up was more frequent in ART-experienced patients than in ART-naive patients, 41.7 versus 11.8%, resistant viruses emerged at comparable follow-up periods, a median of 17.8 and 18.3 months, respectively. In patients receiving zidovudine and lamivudine in their drug regimen, resistance to lamivudine was more frequent than to zidovudine. Two of the three patients, with viruses resistant to PIs, acquired mutations associated with cross-resistance. Strikingly, five (39%) of the 13 patients developed resistances to drugs that they had never received (n = 3) or that they received 18 or 36 months ago (n = 2). Didanosine/stavudine pressure had selected zidovudine-resistant viruses in four patients, and indinavir had selected a nelfinavir-resistant virus in one patient. CONCLUSION: In contrast to other reports from developing countries where patients had received ARVs in an uncontrolled manner, our study showed that implementation of HAART together with good clinical, biological and logistical monitoring can reduce the emergence of resistant strains in Africa.

Once-a-day highly active antiretroviral therapy in treatment-naive HIV-1-infected adults in Senegal.

OBJECTIVES: To study the effectiveness, adherence and tolerance of a once-a-day highly active antiretroviral therapy regimen in adults in Senegal. DESIGN AND METHODS: In a prospective, open-label one-arm study, 40 treatment-naive HIV-1-infected patients took the following three drugs once a day at bedtime: didanosine, lamivudine and efavirenz. The primary endpoint was the percentage of patients with plasma HIV-1 RNA below 500 copies/ml at 6 months. The analysis was done on an intent-to treat basis. RESULTS: Eighty-five per cent of patients were at Centers for Disease Control and Prevention stage B or C and the plasma HIV RNA level was 5.4 +/- 0.4 log(10) copies/ml at baseline. The percentage of patients with plasma HIV-1 RNA below 500 copies/ml at 6 months was 95% [95% confidence interval (CI), 83-99]. The proportions of patients with plasma HIV-1 RNA below 50 copies/ml at months 3, 6, 9, 12 and 15 were 26% (n = 39; 95% CI, 12-39), 78% (n = 40; 95% CI, 65-90), 70% (n = 40; 95% CI, 56-84), 77% (n = 39; 95% CI, 64-90) and 69% (n = 39; 95% CI, 55-84), respectively. The CD4 cell count was 164 +/- 75 x 106/l at baseline and increased by a mean of 199 +/- 101 x 106/l at month 15. Permanent treatment discontinuation was never necessary for serious adverse effects. Adherence was excellent, as shown by plasma drug concentrations and according to the results of the questionnaire. CONCLUSIONS: The once-daily regimen of didanosine, lamivudine and efavirenz was safe, easy-to-take and demonstrated strong antiretroviral and immunologic effects in African patients with advanced HIV infection.

No difference in clinical progression between patients infected with the predominant human immunodeficiency virus type 1 circulating recombinant form (CRF) 02_AG strain and patients not infected with CRF02_AG, in Western and West-Central Africa: a four-year prospective multicenter study.

To compare human immunodeficiency virus (HIV) type 1 disease progression in patients infected by the predominant strain circulating recombinant form (CRF) 02_AG in western and west-central Africa and in patients infected by other strains, a prospective multicenter cohort study was conducted in Cameroon and Senegal. Among the 335 patients, a broad HIV-1 group M subtype diversity was observed in the envelope V3-V5 region, but strain CRF02_AG predominated in both Cameroon and Senegal (61.2% and 62.9%, respectively; P<.8). Multivariate analyses showed no difference between patients infected by CRF02 strains and those infected by other strains in terms of survival (adjusted hazards ratio [HR], 1.16; 95% confidence interval [CI], 0.76-1.78; P=.5), clinical disease progression (HR, 0.79; 95% CI, 0.50-1.25; P=.3), or square root CD4 cell decline (regression coefficient, -0.01; 95% CI, -0.82 to 0.81; P=.9). This study suggests that the predominance of HIV-1 CRF02_AG strain in western and west-central Africa should have no major clinical consequences.

The Senegalese government's highly active antiretroviral therapy initiative: an 18-month follow-up study.

OBJECTIVE: To study the feasibility, effectiveness, adherence, toxicity and viral resistance in an African government HAART initiative. METHODS: A prospective observational cohort study started in Dakar in August 1998. Initial treatment consisted of two nucleoside reverse transcriptase inhibitors and one protease inhibitor. The patients attended monthly medical examinations. Plasma HIV-1 RNA and CD4 cell counts were determined at baseline and every 6 months. Intention-to-treat analyses were performed. RESULTS: Fifty-eight treatment-naive patients, mostly infected by HIV-1 strain CRF02-AG, were enrolled. Most were at an advanced stage of HIV disease (86.2% had AIDS). Adherence was good in 87.9% of patients and treatment was effective in most of them. Thus, HIV-1 RNA was undetectable in 79.6, 71.2, 51.4 and 59.3% of patients at months 1, 6, 12 and 18, respectively and the median viral load reduction was approximately 2.5 log10 copies/ml. The CD4 cell count rose by a median of 82, 147 and 180 x 106 cells/l at months 6, 12 and 18, respectively. At the same time points, the cumulative probability of remaining alive or free of new AIDS-defining events was 94.8, 85.0 and 82.3%. Most adverse effects (80.8%) were mild or moderate and only two cases of drug resistance occurred. CONCLUSION: This study shows that HAART is feasible and well tolerated in African patients. Clinical and biological results were comparable to those seen in western cohorts, despite differences in the HIV-1 subtype distribution and an advanced disease stage when the treatment was initiated. Contrary to other recent studies in Africa, viral resistance rarely emerged.