Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial (original) (raw)
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A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa
The New England journal of medicine, 2015
In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 ...
AIDS, 2011
Objective: Evaluations of CD4 cell count and other prognostic factors on the survival of HIV patients in sub-Saharan Africa are extremely limited. Funders have been reticent to recommend earlier initiation of treatment. We aimed to examine the effect of baseline CD4 cell count on mortality using data from HIV patients receiving combination antiretroviral therapy (cART) in Uganda. Design: Observational study of patients aged at least 14 years enrolled in 10 clinics across Uganda for which The AIDS Support Organization (TASO) has data. Methods: CD4 cell count was stratified into categories (<50, 50-99, 100-149, 150-199, 200-249, 250-299, 300 cells/ml) and Cox proportional hazards regression was used to model the associations between CD4 cell count and mortality. Results: A total of 22 315 patients were included. 1498 patients died during follow-up (6.7%) and 1433 (6.4%) of patients were lost to follow-up. Crude mortality rates (CMRs) ranged from 53.8 per 1000 patient-years [95% confidence interval (CI) 48.8-58.8] among those with CD4 cell counts of less than 50, to 15.7, (95% CI 12.1-19.3) among those with at least 300 cells/ml. Relative to a baseline CD4 cell count of less than 50 cells/ml, the risk of mortality was 0.75 (95% CI 0.65-0.88), 0.60 (95% CI 0.51-0.70), 0.43 (0.37-0.50), and 0.41 (0.33-0.51) for those with baseline CD4 cell counts of 50-99, 100-149, 150-249, and 250 cells/ml, respectively. Conclusion: Earlier initiation of cART is associated with increased survival benefits over deferred treatment.
The Journal of Infectious Diseases, 2010
Background. Few randomized trials comparing antiretroviral therapy (ART) regimens have been conducted in resource-limited settings. Methods. In the Republic of South Africa, antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals 114 years old with a CD4 cell count !200 cells/mL or a prior AIDS diagnosis were randomized to receive efavirenz (EFV) or lopinavir/ritonavir (LPV/r) with either zidovudine (ZDV) plus didanosine (ddI) or stavudine (d4T) plus lamivudine (3TC) in an open-label, 2-by-2 factorial study and followed up for the primary outcome of AIDS or death and prespecified secondary outcomes, including CD4 cell count and viral load changes, treatment discontinuation, and grade 4 events. Results. In total, 1771 persons were randomized and followed up for a median of 24.7 months. AIDS or death occurred in (1) 163 participants assigned EFV and 157 assigned LPV/r (hazard ratio [HR], 1.04 [95% confidence interval {CI}, 0.84-1.30]) and in (2) 170 participants assigned ZDV+ddI and 150 assigned d4T+3TC (HR, 1.15 [95% CI, 0.93-1.44]). HIV RNA levels were lower () and CD4 cell counts were greater () over P ! .001 P ! .01 follow-up for d4T+3TC versus ZDV+ddI. Rates of potentially life-threatening adverse events and overall treatment discontinuation were similar for d4T+3TC and ZDV+ddI; however, more participants discontinued d4T because of toxicity (12.6%) than other treatments (!5%). Conclusion. EFV and LPV/r are effective components of first-line ART. The poorer viral and immune responses with ZDV+ddI and the greater toxicity-associated discontinuation rate with d4T+3TC suggest that these treatments be used cautiously as initial therapy. Trial registration. ClinicalTrials.gov identifier: NCT00342355.
Antiviral Therapy
Background Studies in developed countries have shown highly active antiretroviral therapy (HAART) decreases incidence of severe opportunistic diseases (ODs) in HIV-infected patients beyond that which is expected from changes in CD4+T-cell count. Objective To estimate the independent impact of HAART on reducing ODs and mortality in Côte d'Ivoire. Methods Within two longitudinal studies of HIV-infected adults (1996–2003), we identified time on ‘cotrimoxazole alone’ and ‘HAART plus cotrimoxazole’. WHO stage 3–4 defining events and severe malaria were divided into those preventable and not preventable with cotrimoxazole. Incidence of ODs by CD4 count stratum was estimated using incidence density analysis. CD4+ T-cell count at time of OD was estimated using linear interpolation. Using Poisson regression, we estimated the effect of HAART on OD incidence and mortality by CD4 count stratum. Results Totals of 446 and 135 adults were followed during 6,216 and 3,412 person-months in the co...
AIDS Research and Therapy, 2011
Background There have been few reports of long-term survival of HIV-infected patients on antiretroviral therapy (ART) in Africa managed under near normal health service conditions. Methods Participants starting ART between February 2005 and December 2006 in The AIDS Support (TASO) clinic in Jinja, Uganda, were enrolled into a cluster-randomised trial of home versus facility-based care and followed up to January 2009. The trial was integrated into normal service delivery with patients managed by TASO staff according to national guidelines. Rates of survival, virological failure, hospital admissions and CD4 count over time were similar between the two arms. Data for the present analysis were analysed using Cox regression analyses. Results 1453 subjects were enrolled with baseline median count of 108 cells/μl. Over time, 119 (8%) withdrew and 34 (2%) were lost to follow-up. 197/1453 (14%) died. Mortality rates (95% CI) per 100 person-years were 11.8 (10.1, 13.8) deaths in the first yea...