aCenter for Global Health and Development, Boston University, Boston, MA, USA bDepartment of Epidemiology, Boston University School of Public Health, Boston, MA, USA cHealth Economics and Epidemiology Research Office, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa dDepartment of International Health, Boston University School of Public Health, Boston, MA, USA eRight to Care, Johannesburg, South Africa fClinical HIV Research Unit, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
OBJECTIVES:: To assess outcomes over the first seven years of antiretroviral therapy at Themba Lethu Clinic, Johannesburg, South Africa. DESIGN:: Observational cohort study. METHODS:: Patients are managed according to South African National Treatment Guidelines. Mortality is ascertained through linkage with the national vital registration system. Loss to follow-up is defined as ≥3 months late for the last scheduled appointment. RESULTS:: Between April 2004 and March 2010, 13,227 patients initiated ART, increasing from 1,794 in the year 2004/5 to 2,481 in 2009/10. Median CD4 at ART initiation increased 39% between 2004 and 2009 (82 vs. 114 cells/mm). The proportion who died within one year on ART was below 11% at all time points, while the proportion lost by one year increased from 8.5% in 2004 to 12.1% in 2009 (RR: 1.42; 95%CI: 1.18-1.71).We followed the 1,794 patients initiated in April 2004-March 2005 through August, 2011 for 8,172 person-years. We estimated 25% of patients were lost and 16% died. The overall mortality rate was 3.59/100 PY (95%CI: 3.20-4.02). Of the 1,577 who completed ≥6 months of follow up, 213 (13.5%) failed first-line treatment in a median (IQR) of 25.9 (15.8-41.4) months on treatment. Of those who failed, 141 (66.2%) switched to second-line for a rate of 48.5/100 PY (95%CI: 41.1-57.2). CONCLUSIONS:: Despite some improvements over seven years, more intervention is needed in the first year on treatment to reduce overall attrition.
[Show abstract][Hide abstract] ABSTRACT: Objective:
To explore the impact of expanded eligibility criteria for antiretroviral therapy (ART) on median CD4+ cell count at ART initiation and early mortality on ART.
Analyses included all adults (≥16 years) initiated on first-line ART between August 2004 and July 2012. CD4+ cell count threshold 350 cells per microliter for all adults was implemented in August 2011. Early mortality was defined as any death within 91 days of ART initiation. Trends in baseline CD4+ cell count and early mortality were examined by year (August to July) of ART initiation. Competing risks analysis was used to examine early mortality.
A total of 19,080 adults (67.6% female) initiated ART. Median CD4+ cell count at ART initiation was 110–120 cells per microliter over the first 6 years, increasing marginally to 145 cells per microliter in 2010–2011 and more significantly to 199 cells per microliter in 2011–2012. Overall, there were 875 deaths within 91 days of ART initiation; early mortality rate was 19.4 per 100 person-years [95% confidence interval (CI) 18.2 to 20.7]. After adjustment for sex, age, baseline CD4+ cell count, and concurrent tuberculosis (TB), there was a 46% decrease in early mortality for those who initiated ART in 2011–2012 compared with the reference period 2008–2009 (subhazard ratio, 0.54; 95% CI: 0.41 to 0.71).
Since the expansion of eligibility criteria, there is evidence of earlier access to ART and a significant reduction in early mortality rate in this primary health care programme. These findings provide strong support for national ART policies and highlight the importance of earlier ART initiation for achieving reductions in HIV-related mortality.
[Show abstract][Hide abstract] ABSTRACT: Background. High rates of second-line antiretroviral treatment (ART) failure are reported. The association with resistance and nonadherence on switching to second-line ART requires clarification.
Methods. Using prospectively collected data from patients in South Africa, we constructed a cohort of patients switched to second-line ART (1 January 2003 through 31 December 2008). Genotyping and drug concentrations (lamivudine, nevirapine, and efavirenz) were measured on stored samples preswitch. Their association with viral load (VL) <400 copies/mL by 15 months was assessed using modified Poisson regression.
Results. One hundred twenty-two of 417 patients (49% male; median age, 36 years) had genotyping (n = 115) and/or drug concentrations (n = 80) measured. Median CD4 count and VL at switch were 177 cells/µL (interquartile range [IQR], 77–263) and 4.3 log10 copies/mL (IQR, 3.8–4.7), respectively. Fifty-five percent (n = 44/80) had subtherapeutic drug concentrations preswitch. More patients with therapeutic vs subtherapeutic ART had resistance (n = 73): no major mutations (3% vs 51%), nonnucleoside reverse transcriptase inhibitor (94% vs 44%), M184V/I (94% vs 26%), and ≥1 thymidine analogue mutations (47% vs 18%), all P = .01; and nucleoside reverse transcriptase inhibitor (NRTI) cross-resistance mutations (26% vs 13%, P = .23). Following switch, 68% (n = 83/122) achieved VL <400 copies/mL. Absence of NRTI mutations and subtherapeutic ART preswitch were associated with failure to achieve VL <400 copies/mL.
Conclusions. Nonadherence, suggested by subtherapeutic ART with/without major resistance mutations, significantly contributed to failure when switching regimen. Unresolved nonadherence, not NRTI resistance, drives early second-line failure.
The Journal of Infectious Diseases 08/2013; 209(5). DOI:10.1093/infdis/jit411 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Evaluate the effect of antiretroviral therapy (ART) on South African HIV patients' economic well being, as indicated by symptoms, normal activities, employment, and external support, during the first 5 years on treatment.
Prospective cohort study of 879 adult patients at public or nongovernmental clinics enrolled before ART initiation or on ART less than 6 months and followed for 5.5 years or less. Patients were interviewed during routine clinic visits. Outcomes were estimated using population-averaged logistic regression and reported as proportions of the cohort experiencing outcomes by duration on ART.
For patients remaining in care, outcomes improved continuously and substantially, with all differences between baseline and 5 years statistically significant (P < 0.05) and continued significant improvement between year 3 and year 5. The probability of reporting pain last week fell from 69% during the three months before starting ART to 17% after 5 years on ART and fatigue from 62 to 7%. The probability of not being able to perform normal activities in the previous week fell from 47 to 5% and of being employed increased from 32 to 44%; difficulty with job performance among those employed fell from 56 to 6%. As health improved, the probability of relying on a caretaker declined from 81 to less than 1%, and receipt of a disability grant, which initially increased, fell slightly over time on ART.
Results from one of the longest prospective cohorts tracking economic outcomes of HIV treatment in Africa suggest continuous improvement during the first 5 years on treatment, confirming the sustained economic benefits of providing large-scale treatment.
AIDS (London, England) 09/2013; 28(3). DOI:10.1097/QAD.0000000000000053 · 5.55 Impact Factor
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