Isabelle Lanièce

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

ObjectiveTo study the feasibility, effectiveness, adherence, toxicity and viral resistance in an African government HAART initiative. MethodsA 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. ResultsFifty-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 ∼2.5 log10 copies/ml. The CD4 cell count rose by a median of 82, 147 and 180 × 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. ConclusionThis 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.

Mortality and causes of death in adults receiving highly active antiretroviral therapy in Senegal: a 7-year cohort study.

Objectives:To evaluate survival and investigate causes of death among HIV-1 infected adults receiving HAART in Senegal. Design:An observational prospective cohort. Methods:Mortality was assessed in the first patients enrolled between August 1998 and April 2002 in the Senegalese antiretroviral drug access initiative. First-line regimen combined two nucleoside reverse transcriptase inhibitors and either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor. The most likely causes of death were ascertained through medical records or post-mortem interviews (verbal autopsy). Results:Four hundred and four patients (54.7% women) were enrolled in the study and were followed for a median of 46 months (interquartile range: 32–57 months) after HAART initiation. At baseline, 5% were antiretroviral therapy (ART) non-naive, 39 and 55% were respectively at CDC stage B and C, median age, CD4 cell count and viral load were 37 years, 128 cells/μl and 5.2 log cp/ml, respectively. Ninety-three patients died during follow-up and the overall incidence rate of death was 6.3/100 person-years [95% confidence interval (CI), 5.2–7.7]. During the first year after HAART initiation, 47 patients died and seven were lost to follow-up, yielding to a probability of dying of 11.7% (95% CI, 8.9–15.3%). The death rate, which was highest during the first year after HAART initiation, decreased with time yielding a cumulative probability of dying of 17.4% (95% CI, 13.9–21.5%) and 24.6% (95% CI, 20.4–29.4%) at 2 and 5 years. Causes of death were ascertained in 76 deaths. Mycobacterial infections, neurotropic infections and septicaemia were the most frequent likely causes of death. Conclusions:This study underlines the early mortality pattern after HAART initiation and highlights the leading role of mycobacterial infections in the causes of death.

Adherence to HAART and its principal determinants in a cohort of Senegalese adults.

BackgroundAccess to programmes providing highly active antiretroviral therapy (HAART) is recent in Africa. In Senegal, a national initiative was launched in 1998. The capacity of African patients to adhere to complex antiretroviral treatments (ARV) is largely unknown. MethodsWe assessed adherence and identified the main reasons for treatment interruption in a prospective observational cohort of patients participating in an ARV access programme in Dakar, Senegal. Adherence was estimated each month on the basis of the patients stated consumption and on the proportion of the prescribed dose returned unused to the dispensing pharmacy. A total of 158 patients were studied between November 1999 and October 2001. ResultsA cross-section analysis showed that the stated level of adherence was high: on average, over the study period, the patients said they had taken 91% of each monthly dose and that they had taken the full monthly dose during two-thirds of the months studied. Adherence tended to be better among patients who were required to make little or no contribution to the cost of their treatment, through an appropriate pricing structure. Adherence was also better with efavirenz-containing regimens than with indinavir-containing regimens. ConclusionThese results show that adherence to HAART can be as high in Africa as that generally observed in industrialized countries, and that the cost and type of drug regimen must be taken into account when designing ARV access programmes for poor communities.

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.

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

ObjectiveTo 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). MethodsA 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. ResultsAt 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 anti-tubercular 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. ConclusionIn 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.

Access to antiretroviral drugs and Aids management in Senegal

ObjectivesDescription and analysis of the Senegalese Antiretroviral Drug Access Initiative (ISAARV), the first governmental highly active antiretroviral therapy (HAART) treatment programme in Africa, launched in 1998. Methods and resultsISAARV was initially an experimental project designed to evaluate the feasibility, efficacy and acceptability of HAART in an African context. It was based on four principles: collective definition of the strategy, with involvement of the health professionals who would be called on to execute the programme; matching the objectives to available means (gradual enrollment according to drug availability); monitoring by several research programmes; and ongoing adaptation of treatment and follow-up according to the latest international recommendations.Persons qualifying for antiretroviral (ARV) therapy are selected on the basis of immunological and clinical criteria, regardless of economic and social considerations. A system of subsidies was created to favor access to ARV. Following the ARV price reductions that occurred in November 2000, 100% subsidies were created for the poorest participants. Optimal adherence was ensured by monthly follow-up by pharmacists and support groups held by social workers and patient associations. The chosen supply and distribution system allowed drug dispensing to be strictly controlled. ConclusionThe ISAARV programme demonstrates that HAART can be successfully prescribed in Africa. This experience has served as the basis for the creation of a national treatment programme in Senegal planned to treat 7000 patients by 2006.

A 84-month follow up of adherence to HAART in a cohort of adult Senegalese patients

Objectivesu2002 To assess long‐term adherence of the first HIV‐1 patients receiving highly active antiretroviral therapy (HAART) in Senegal, and to identify the main determinants of adherence.

Revisiting Long-Term Adherence to Highly Active Antiretroviral Therapy in Senegal Using Latent Class Analysis

Background:Adherence is one of the main predictors of antiretroviral treatment success. A governmental initiative was launched in 1998 for HIV-infected patients in Senegal to provide access to highly active antiretroviral therapy. Methods:Between August 1998 and April 2002, 404 adult patients were enrolled. Adherence measurements, defined as pills taken/pills prescribed, were assessed between November 1999 and April 2009 using a pill count along with a questionnaire for 330 patients. Predictors of adherence were explored through a random-intercept Tobit model and a latent class analysis (LCA) was performed to identify adherence trajectories. We also performed a survival analysis taking into account gender and latent adherence classes. Results:Median treatment duration was 91 months (interquartile range, 84-101). On average, adherence declined by 7% every year, was 30% lower for patients taking indinavir, and 12% higher for those receiving cotrimoxazole prophylaxis. Based on the predicted probability of having an adherence ≥ 95%, LCA revealed 3 adherence behaviors and a better adherence for women. A quarter of patients had a high adherence trajectory over time and half had an intermediate one. Male gender and low adherence behavior over time were independently associated with a higher mortality rate. Conclusions:This study shows that an overall good adherence can be obtained in the long term in Senegal. LCA suggests a better adherence for women and points out a large subsample of patients with intermediate level of adherence behavior who are at risk for developing resistance to antiretroviral drugs. This study warrants further research into gender issues.