Reduction in Early Mortality on Antiretroviral Therapy for Adults in Rural South Africa Since Change in CD4(+) Cell Count Eligibility Criteria

1Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa 2Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK 3Department of Infection and Population Health, University College London, UK 4The Brighton Doctoral College, Brighton and Sussex Medical School, UK 5University College London Institute of Child Health, London, UK.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 06/2013; 65(1). DOI: 10.1097/QAI.0b013e31829ceb14
Source: PubMed


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.

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Available from: Richard Lessells, Mar 26, 2014
    • "Further, many patients who initiate ART often do so late in the course of their HIV disease when already severely immunocompromised, that is, well below the recommended CD4 threshold (UNA- IDS 2012), which substantially increases the risk of death (Fairall et al. 2008; Lawn et al. 2008; Lessells et al. 2014). Although this is gradually improving with expanded treatment eligibility criteria (Lessells et al. 2014), it remains unsatisfactory from public health and individual standpoints. For patients to initiate ART as soon as they are eligible (Rosen & Fox 2011), it is important to provide a continuum of care, which starts as soon as a person is diagnosed HIV-positive (Horstmann et al. 2010; Kranzer et al. 2010). "
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    ABSTRACT: Objective To quantify time from entry in HIV care until Antiretroviral therapy (ART) initiation and identify factors associated with ART initiation in rural KwaZulu-Natal, South Africa.Methods Adults ≥16 years entering the decentralised Hlabisa ART programme between 2007 and 2011 were followed until June 2013. Median survival times to ART initiation from date of programme entry and from date of ART eligibility were estimated with Kaplan–Meier methods. Associated factors were evaluated in Cox regressions, censoring for deaths.ResultsOf 37 749 adults (71.6% female), 17 638 (46.7%) initiated ART. Nearly half (46.9%) met the CD4 criteria for treatment eligibility at programme entry. Among the 20 039 individuals not yet ART-eligible at entry, only 62.5% were retained in care with at least one further CD4 measurement, of whom 6688 subsequently became ART-eligible. Overall, 65.5% of the 24 398 ART-eligible individuals initiated ART over the study period. ART initiation was more likely in women (P < 0.001), in individuals ≥ 25 years old (P < 0.001) and in patients with low CD4 count (P < 0.001). Patients who became eligible during follow up were significantly more likely to initiate ART than those eligible at programme entry (72.6% vs. 62.9%, Adjusted Hazard Ratio = 1.46; 95% Confidence Interval [1.41–1.51]), adjusting for sex, age, year and CD4 count at eligibility.Conclusions In this rural programme, continuation of care remains challenging, especially in men and younger adults. ART initiation is more likely in those engaged prior eligibility than in those entering HIV care only late in their HIV disease.
    No preview · Article · Mar 2014 · Tropical Medicine & International Health
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    ABSTRACT: Little is known about the variability of CD4 counts in the general population of sub-Saharan Africa countries affected by the HIV epidemic. We investigated factors associated with CD4 counts in a rural area in South Africa with high HIV prevalence and high antiretroviral treatment (ART) coverage. CD4 counts, health status, body mass index (BMI), demographic characteristics and HIV status were assessed in 4990 adult resident participants of a demographic surveillance in rural KwaZulu-Natal in South Africa; antiretroviral treatment duration was obtained from a linked clinical database. Multivariable regression analysis, overall and stratified by HIV status, was performed with CD4 count levels as outcome. Median CD4 counts were significantly higher in women than in men overall (714 vs. 630 cells/µl, p<0.0001), both in HIV-uninfected (833 vs. 683 cells/µl, p<0.0001) and HIV-infected adults (384.5 vs. 333 cells/µl, p<0.0001). In multivariable regression analysis, women had 19.4% (95% confidence interval (CI) 16.1-22.9) higher CD4 counts than men, controlling for age, HIV status, urban/rural residence, household wealth, education, BMI, self-reported tuberculosis, high blood pressure, other chronic illnesses and sample processing delay. At ART initiation, HIV-infected adults had 21.7% (95% CI 14.6-28.2) lower CD4 counts than treatment-naive individuals; CD4 counts were estimated to increase by 9.2% (95% CI 6.2-12.4) per year of treatment. CD4 counts are primarily determined by sex in HIV-uninfected adults, and by sex, age and duration of antiretroviral treatment in HIV-infected adults. Lower CD4 counts at ART initiation in men could be a consequence of lower CD4 cell counts before HIV acquisition.
    Full-text · Article · Jul 2013 · PLoS ONE
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