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
Laurent C.,Montpellier University |
Kouanfack C.,Central Hospital |
Laborde-Balen G.,French Ministry of Foreign Affairs |
Aghokeng A.F.,Montpellier University |
And 16 more authors.
The Lancet Infectious Diseases | Year: 2011
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 WHO's 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. © 2011 Elsevier Ltd.
Gabillard D.,French Institute of Health and Medical Research |
Gabillard D.,University of Bordeaux 1 |
Lewden C.,French Institute of Health and Medical Research |
Lewden C.,University of Bordeaux 1 |
And 20 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2013
Background: In resource-limited countries, estimating CD4-specific incidence rates of mortality and morbidity among patients receiving antiretroviral therapy (ART) may help assess the effectiveness of care and treatment programmes, identify program weaknesses, and inform decisions. Methods: We pooled data from 13 research cohorts in 5 sub- Saharan African (Benin, Burkina Faso, Cameroon, Cote d'Ivoire, and Senegal) and 2 Asian (Cambodia and Laos) countries. HIVinfected adults (18 years and older) who received ART in 1998- 2008 and had at least one CD4 count available were eligible. Changes in CD4 counts over time were estimated by a linear mixed regression. CD4-specific incidence rates were estimated as the number of first events occurring in a given CD4 stratum divided by the time spent within the stratum. Results: Overall 3917 adults (62% women) on ART were followed up during 10,154 person-years. In the #50, 51-100, 101-200, 201- 350, 351-500, 501-650, and .650 cells/mm3 CD4 cells strata, death rates were 20.6, 11.8, 6.7, 3.3, 1.8, 0.9, and 0.3 per 100 person-years; AIDS rates were 50.5, 32.9, 11.5, 4.8, 2.8, 2.2, and 2.2 per 100 person-years; and loss-to-follow-up rates were 4.9, 6.1, 3.5, 3.1, 2.9, 1.7, and 1.2 per 100 person-years, respectively. Mortality and morbidity were higher during the first year after ART initiation. Conclusions: In these resource-limited settings, death and AIDS rates remained substantial after ART initiation, even in individuals with high CD4 cell counts. Ensuring earlier ART initiation and optimizing case finding and treatment for AIDS-defining diseases should be seen as priorities. Copyright © 2012 by Lippincott Williams & Wilkins.
Ndziessi G.,French Institute of Health and Medical Research |
Ndziessi G.,Aix - Marseille University |
Cohen J.,French Institute of Health and Medical Research |
Cohen J.,Aix - Marseille University |
And 18 more authors.
PLoS ONE | Year: 2013
Objectives: Using cohort data nested in a randomized trial conducted in Cameroon, this study aimed to investigate time trends and predictors of the susceptibility to transmitting HIV during the first 24 months of treatment. Methods: The outcome, susceptibility to transmitting HIV, was defined as reporting inconsistent condom use and experiencing incomplete virological suppression. Mixed logistic regressions were performed to identify predictors of this outcome among 250 patients reporting to have had sexual relationships either with HIV-negative or unknown HIV status partner(s). Results: Despite an initial decrease from 76% at M0 to 50% at M6, the rate of inconsistent condom use significantly increased from M12 (59%) to M24 (66%) (p = 0.017). However, the proportion of patients susceptible to transmitting HIV significantly decreased over follow-up from 76% at M0, to 50% at M6, 31% at M12 and 27% at M24 (p<0.001). After controlling for age, gender and intervention group, we found that perceiving healthcare staff's readiness to listen as poor (adjusted odds ratios (AOR) [95% Confidence Interval (CI)] = 1.87 [1.01-3.46]), reporting to have sexual relationships more than once per week (AOR [95%CI] = 2.52 [1.29-4.93]), having more than one sexual partner (AOR [95%CI] = 2.53 [1.21-5.30]) and desiring a/another child (AOR [95%CI] = 2.07 [1.10-3.87]) were all associated with a higher risk of being susceptible to transmitting HIV. Conversely, time since ART initiation (AOR [95%CI] = 0.66 [0.53-0.83] for an extra 6 months and ART adherence (AOR [95%CI] = 0.33 [0.15-0.72]) were significantly associated with a lower risk of being susceptible to transmitting HIV. Conclusions: The decrease observed in the susceptibility to transmitting HIV suggests that fear of behavioural disinhibition should not be a barrier to universal access to ART. However, developing adequate preventive interventions matching patients' expectations -like the desire to have children- and strengthening healthcare staff's counselling skills are urgently needed to maximize the impact of ART in slowing the HIV epidemic. © 2013 Ndziessi et al.
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
Boyer S.,French Institute of Health and Medical Research |
Boyer S.,Aix - Marseille University |
March L.,French Institute of Health and Medical Research |
March L.,Aix - Marseille University |
And 17 more authors.
The Lancet Infectious Diseases | Year: 2013
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$95 (scenario 1; Abbott RealTime HIV-1 assay) or $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 ($3670-3800) and an alternative lower threshold of $2385 to determine cost-effectiveness. We assessed uncertainty with one-way sensitivity analyses and cost-effectiveness acceptability curves. Findings: 188 participants who underwent LAB and 197 who underwent CLIN were followed up for at least 6 months. In scenario 1, LAB increased costs by a mean of $489 (SD 430) per patient and saved 0·103 life-years compared with CLIN (ICER of $4768 [95% CI 3926-5613] per LYS). In scenario 2, the incremental mean cost of LAB was $343 (SD 425) -ie, an ICER of $3339 (2507-4173) per LYS. A combined strategy in which LAB would only be used in patients starting ART with a CD4 count of 200 cells per μL or fewer suggests that 0·120 life-years would be saved at an additional cost of $259 per patient in scenario 1 (ICER of $2167 [95% CI 1314-3020] per LYS) and $181 in scenario 2 (ICER of $1510 [692-2329] per LYS) when compared with CLIN. Interpretation: Laboratory monitoring was not cost effective in 2006-10 compared with clinical monitoring when the Abbott RealTime HIV-1 assay was used according to the $3670 cost-effectiveness threshold (three times per-person GDP in Cameroon), but it might be cost effective if a generic in-house assay is used. Funding: French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau (ESTHER). © 2013 Elsevier Ltd.