Charles Kouanfack

Effectiveness and safety of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine in HIV-1-infected adults in Cameroon: open-label multicentre trial

BACKGROUND Generic fixed-dose combinations have been prequalified by WHO to treat HIV-infected patients in resource-limited countries. Despite their widespread use they are, however, not yet recommended by some of the major donor agencies owing to scarcity of clinical data on effectiveness, safety, and quality. We aimed to assess these issues for one of the most frequently prescribed treatments in Africa, a generic fixed-dose combination of nevirapine, stavudine, and lamivudine. METHODS 60 patients were followed in an open-label, 24-week multicentre trial in Cameroon. All patients received one tablet of the fixed-dose combination drug twice daily. The primary outcome measure was the proportion of patients with viral load less than 400 copies per mL at the end of the study period, in an intention-to-treat analysis. FINDINGS At baseline, 92% of patients (n=55) had AIDS; median CD4 count was 118 cells per microL (IQR 78-167) and median plasma HIV-1 RNA was 104?736 copies per mL (40804-243787). The proportion of patients with undetectable viral load (<400 copies per mL) after 24 weeks of treatment was 80% (95% CI 68-89). Median (IQR) change in viral load was -3.1 log10 copies per mL (-2.5 to -3.6) and in CD4 count 83 cells per microL (40-178). The probability of remaining alive or free of new AIDS-defining events was 0.85 (95% CI 0.73-0.92). Frequency of disease progression was 32.0 (95% CI 16.6-61.5), severe adverse effects 17.8 (7.4-42.7), and genotypic resistance mutations 7.1 (1.8-28.4) per 100 person-years. Mean reported adherence rate was 99%. Median drug concentrations in tablets were 96% of expected values for nevirapine, 89% for stavudine, and 99% for lamivudine. INTERPRETATION Our findings lend support to use and funding of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine as first-line antiretroviral treatment in developing countries.

The Cameroon Mobile Phone SMS (CAMPS) Trial: A Randomized Trial of Text Messaging versus Usual Care for Adherence to Antiretroviral Therapy

Background Mobile phone technology is a novel way of delivering health care and improving health outcomes. This trial investigates the use of motivational mobile phone text messages (SMS) to improve adherence to antiretroviral therapy (ART) over six months. Methodology/Principal Findings CAMPS was a single-site randomized two-arm parallel design trial in Yaoundé, Cameroon. We enrolled and randomized HIV-positive adults on ART, aged 21 years and above to receive a weekly standardized motivational text message versus usual care alone. The primary outcome was adherence measured using a visual analogue scale (VAS), number of doses missed (in the week preceding the interview) and pharmacy refill data. Outcomes were measured at 3 and 6 months. Service providers and outcome assessors were blinded to allocation. Analysis was by intention-to-treat. Between November and December 2010, 200 participants were randomized, with 101 in the intervention group and 99 in the control group. At 6 months, overall retention was 81.5%. We found no significant effect on adherence by VAS>95% (risk ratio [RR] 1.06, 95% confidence interval [CI] 0.89, 1.29; p = 0.542; reported missed doses (RR 1.01, 95% CI 0.87, 1.16; p>0.999) or number of pharmacy refills (mean difference [MD] 0.1, 95% CI: 0.23, 0.43; p = 0.617. One participant in the intervention arm reported a possible disclosure of status. Conclusions/Significance Standardized motivational mobile phone text messages did not significantly improve adherence to ART in this study. Other types of messaging or longer term studies are recommended. Registration 1. Pan-African Clinical Trials Registry; PACTR201011000261458 2. Clinicaltrials.gov; NCT01247181

Monitoring of HIV viral loads, CD4 cell counts, and clinical assessments versus clinical monitoring alone for antiretroviral therapy in rural district hospitals in Cameroon (Stratall ANRS 12110/ESTHER): a randomised non-inferiority trial

BACKGROUND Scaling up of antiretroviral therapy in low-resource countries is done on the basis of decentralised, integrated HIV care in rural facilities; however, laboratory monitoring is generally unavailable. We aimed to assess the effectiveness and safety of clinical monitoring alone (CLIN) in terms of non-inferiority to laboratory and clinical monitoring (LAB). METHODS We did a randomised, open-label, non-inferiority trial in nine rural district hospitals in Cameroon. Eligible participants were adults (≥18 years) infected with HIV-1 group M (WHO disease stage 3-4) who had not previously received antiretroviral therapy, and were followed-up for 2 years by health-care workers in routine activities. We randomly assigned participants (1:1) to CLIN or LAB (counts of HIV viral load and CD4 cell every 6 months) groups with a computer-generated list. The primary outcome was non-inferiority of CLIN to LAB in terms of increase in CD4 cell count with a non-inferiority margin of 25%. We did all analyses in participants who attended at least one follow-up visit. This trial is registered with ClinicalTrials.gov, number NCT00301561. FINDINGS 238 (93%) of 256 participants assigned to CLIN and 221 (93%) of 237 assigned to LAB were eligible for analysis. CLIN was not non-inferior to LAB; the mean increase in CD4 cell count was 175 cells per μL (SD 190, 95% CI 151-200) with CLIN and 206 (190, 181-231) with LAB (difference -31 [-63 to 2] and non-inferiority margin -52 [-58 to -45]). Furthermore, in the predefined secondary outcome of treatment changes, 13 participants (6%) in the LAB group switched to second-line regimens whereas no participants in the CLIN group did so (p<0·0001). By contrast, other predefined secondary outcomes were much the same in both groups-viral suppression (<40 copies per mL; 465 [49%] of 952 measurements in CLIN vs 456 [52%] of 884 in LAB), HIV resistance (23 [10%] of 238 participants vs 22 [10%] of 219 participants), mortality (44 [18%] of 238 vs 32 [14%] of 221), disease progression (85 [36%] of 238 vs 64 [29%] of 221), adherence (672 [63%] of 1067 measurements vs 621 [61%] of 1011), loss to follow-up (21 [9%] of 238 vs 17 [8%] of 221), and toxic effects (46 [19%] of 238 vs 56 [25%] of 221). INTERPRETATION Our findings support WHOs recommendation for laboratory monitoring of antiretroviral therapy. However, the small differences that we noted between the strategies suggest that clinical monitoring alone could be used, at least temporarily, to expand antiretroviral therapy in low-resource settings. FUNDING French National Agency for Research on AIDS (ANRS) and Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau (ESTHER).

Low Levels of Antiretroviral-Resistant HIV Infection in a Routine Clinic in Cameroon that Uses the World Health Organization (WHO) Public Health Approach to Monitor Antiretroviral Treatment and Adequacy with the WHO Recommendation for Second-Line Treatment

A cross-sectional study, performed at a routine human immunodeficiency virus (HIV)/AIDS clinic in Cameroon that uses the World Health Organization public health approach, showed low rates of virological failure and drug resistance at 12 and 24 months after initiation of antiretroviral therapy. Importantly, the cross-sectional study also showed that the World Health Organization recommendation for second-line treatment would be effective in almost all patients with HIV drug resistance mutations.

Scale-up of antiretroviral treatment in sub-Saharan Africa is accompanied by increasing HIV-1 drug resistance mutations in drug-naive patients.

Objectives:To evaluate the frequency and progression over time of the WHO-defined transmitted HIV-1 drug resistance mutations (DRMs) among antiretroviral treatment (ART)-naive HIV-1-infected patients in Cameroon. Design:We analyzed HIV-1 DRM data generated from 369 ART-naive individuals consecutively recruited between 1996 and 2007 in urban and rural areas in Cameroon. Methods:HIV-1 drug resistance genotyping was performed in the pol gene using plasma samples and surveillance DRMs were identified using the 2009 WHO-DRM list. Results:We observed in Yaounde, the capital city, an increasing prevalence of DRMs over time: 0.0% (none of 61 participants) in 1996–1999; 1.9% (one of 53 participants) in 2001; 4.1% (two of 49 participants) in 2002; and 12.3% (10 of 81 participants) in 2007. In the rural areas with more recently implemented ART programs, we found DRMs in six of 125 (4.8%) ART-naive individuals recruited in 2006–2007. DRMs identified in both areas included resistance mutations to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) that might impair the efficacy of available first-line and second-line treatments. Conclusion:This report showed an increase in transmitted DRMs in areas where antiretroviral drugs were introduced earlier, although other factors such as natural viral polymorphisms and acquired DRMs through exposure to antiretroviral cannot be totally excluded. Further surveillances are needed to confirm this evolution and inform public health policies on adequate actions to help limit the selection and transmission of drug-resistant HIV, while scaling up access to ART in developing countries.

Tolerability and Effectiveness of First-Line Regimens Combining Nevirapine and Lamivudine Plus Zidovudine or Stavudine in Cameroon

We compared the tolerability and effectiveness of two major first-line regimens used in resource-limited settings, namely zidovudine-lamivudine-nevirapine and stavudine-lamivudine-nevirapine. HIV-1-infected adults in Cameroon were enrolled in a prospective cohort study between 2001 and 2003. They were eligible if they had AIDS or a CD4 cell count below 350/mm(3), a Karnofsky score over 50%, and no contraindications to antiretroviral treatment. The patients were followed up to 2 years. Of 169 patients, 85 received zidovudine-lamivudine-nevirapine and 84 stavudine-lamivudine-nevirapine. The incidence rates of treatment changes, death, drug resistance, and severe adverse effects were, respectively, 12.0 [95% confidence interval (CI) 7.2-19.9] and 10.9 (CI 6.4-18.3) per 100 person-years; 5.7 (CI 2.8-11.4) and 7.6 (CI 4.2-13.7); 2.9 (CI 1.1-7.7) and 5.0 (CI 2.4-10.6); and 41.7 (CI 30.2-57.6) and 49.1 (CI 36.1-66.6). The Kaplan-Meier curves for the likelihood of remaining on the initial regimen (p = 0.8) and for survival (p = 0.5) did not differ significantly between the groups. In Cox multivariate analysis only a lower baseline CD4 cell count was associated with death (p < 0.001). The proportion of patients with undetectable viral load and the increase in the CD4 cell count were similar in the two groups. Anemia was rare (4% vs. 6%). Five cases of severe peripheral neuropathy and one case of lipodystrophy occurred. This study suggests that the zidovudine-lamivudine-nevirapine combination is a safe first-line treatment, even in settings with few laboratory resources. In view of stavudine toxicity, these results support recommendations calling for a gradual switch from stavudine- to zidovudine-based regimens.

Monitoring of HIV viral load, CD4 cell count, and clinical assessment versus clinical monitoring alone for antiretroviral therapy in low-resource settings (Stratall ANRS 12110/ESTHER): a cost-effectiveness analysis.

BACKGROUND In low-income countries, the use of laboratory monitoring of patients taking antiretroviral therapy (ART) remains controversial in view of persistent resource constraints. The Stratall trial did not show that clinical monitoring alone was non-inferior to laboratory and clinical monitoring in terms of immunological recovery. We aimed to evaluate the costs and cost-effectiveness of the ART monitoring approaches assessed in the Stratall trial. METHODS The randomised, controlled, non-inferiority Stratall trial was done in a decentralised setting in Cameroon. Between May 23, 2006, and Jan 31, 2008, ART-naive adults were randomly assigned (1:1) to clinical monitoring (CLIN) or viral load and CD4 cell count plus clinical monitoring (LAB) and followed up for 24 months. We calculated costs, number of life-years saved (LYS), and incremental cost-effectiveness ratios (ICERs) with data from patients who had been followed up for at least 6 months. We considered two cost scenarios in which viral load plus CD4 cell count tests cost either US

Long-term safety, effectiveness and quality of a generic fixed-dose combination of nevirapine, stavudine and lamivudine.

95 (scenario 1; Abbott RealTime HIV-1 assay) or

Antiretroviral drug resistance and routine therapy, Cameroon.

63 (scenario 2; generic assay). We compared ICERs with a WHO-recommended threshold of three times the per-person gross domestic product (GDP) for Cameroon (

Adherence to antiretroviral treatment in HIV-positive patients in the Cameroon context: promoting the use of medication reminder methods.

3670-3800) and an alternative lower threshold of