Population-Based CD4 Counts in a Rural Area in South Africa with High HIV Prevalence and High Antiretroviral Treatment Coverage

Malaza, Abraham; Mossong, Joël; Bärnighausen, Till; Viljoen, Johannes; Newell, Marie‐Louise

doi:10.1371/journal.pone.0070126

Cited by 40 publications

(43 citation statements)

References 47 publications

(54 reference statements)

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“…The study population was predominantly female, consistent with previously reported data [9,13,14], and probably reflecting higher population‐level CD4 cell counts among women [15] and the different entry points into HIV care. Previous work did not find any association between sex and disease progression pre‐ART initiation [4]; however, mortality after ART initiation is consistently higher in men [16].…”

Section: Discussionsupporting

confidence: 89%

Time to eligibility for antiretroviral therapy in adults with CD4 cell count > 500 cells/μL in rural KwaZulu‐Natal, South Africa

2015

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ObjectivesUnderstanding of progression to antiretroviral therapy (ART) eligibility and associated factors remains limited. The objectives of this analysis were to determine the time to ART eligibility and to explore factors associated with disease progression in adults with early HIV infection.MethodsHIV-infected adults (≥ 18 years old) with CD4 cell count > 500 cells/μl were enrolled in the study at three primary health care clinics, and a sociodemographic, behavioural and partnership-level questionnaire was administered. Participants were followed 6-monthly and ART eligibility was determined using a CD4 cell count threshold of 350 cells/μl. Kaplan − Meier and Cox proportional hazard regression modelling were used in the analysis.ResultsA total of 206 adults contributed 381 years of follow-up; 79 (38%) reached the ART eligibility threshold. Median time to ART eligibility was shorter for male patients (12.0 months) than for female patients (33.9 months). Male sex [adjusted hazard ratio (aHR) 3.13; 95% confidence interval (CI) 1.82–5.39], residing in a household with food shortage in the previous year (aHR 1.58; 95% CI 0.99–2.54), and taking nutritional supplements in the first 6 months after enrolment (aHR 2.06; 95% CI 1.11–3.83) were associated with shorter time to ART eligibility. Compared with reference CD4 cell count ≤ 559 cells/μl, higher CD4 cell count was associated with longer time to ART eligibility [aHR 0.46 (95% CI 0.25–0.83) for CD4 cell count 560–632 cells/μl; aHR 0.30 (95% CI 0.16–0.57) for CD4 cell count 633–768 cells/μl; and aHR 0.17 (95% CI 0.08–0.38) for CD4 cell count > 768 cells/μl].ConclusionsOver one in three adults with CD4 cell count > 500 cells/μl became eligible for ART at a CD4 cell count threshold of 350 cells/μl over a median of 2 years. The shorter time to ART eligibility in male patients suggests a possible need for sex-specific pre-ART care and monitoring strategies.

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Section: Discussionsupporting

confidence: 89%

Time to eligibility for antiretroviral therapy in adults with CD4 cell count > 500 cells/μL in rural KwaZulu‐Natal, South Africa

2015

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“…The cohorts demographics are characteristic of HIV epidemiology in South Africa, where patients frequently present with advanced disease, women invariably being younger . Median CD4 counts were low, although somewhat higher in women, a feature previously observed . Since 2007, given significant policy change and a public program, more than half of the cohort were on HAART; and this likely contributed to the prevalent finding of DILI …”

Section: Discussionmentioning

confidence: 69%

A clinicopathological cohort study of liver pathology in 301 patients with human immunodeficiency virus/acquired immune deficiency syndrome

Sonderup

Wainwright²,

Hall³

et al. 2015

Hepatology

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Liver disease complicates human immunodeficiency virus (HIV)/acquired immune deficiency syndrome; however, liver pathology data are limited, particularly from high HIV prevalence countries. We investigated the spectrum and clinicopathological correlates of liver pathology in a high HIV burden setting. In a single-center study, all HIV/acquired immune deficiency syndrome patients with complete clinical and demographic data who underwent liver biopsy were analyzed and clinicopathologically assessed by hepatologists and one of two experienced liver pathologists. We evaluated 301 patients, with a median age of 34 (interquartile range 29-40) years. Women (n 5 143) were younger than men (n 5 158), with a median age of 33 (interquartile range 28-37) versus 35 (interquartile range 31-41) years, P 5 0.001. The majority, 76.1%, were black African. Median CD4 at time of biopsy was 127 (52-260) cells/mm 3 . Drug-induced liver injury was the predominant finding (42.2%), followed by granulomatous inflammation (29%), steatosis/ steatohepatitis (19.3%), hepatitis B (19%), and hepatitis C coinfection (3.3%), with more than one pathology in 16.2%. With granulomatous inflammation, 52% met the criteria for tuberculosis immune reconstitution syndrome. By univariate analysis, cotrimoxazole and antiretroviral therapy conferred risk for drug injury (odds ratio [OR] 5 2.78 [1.72-4.48], P < 0.001; OR 5 1.69 [1.06-2.68], P 5 0.027). In multivariate analysis, cotrimoxazole was associated with a cholestatic or ductopenic injury (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).89], P < 0.001; OR 5 17.6 [3.26-95.3], P < 0.0001); efavirenz was associated with nonspecific hepatitis or submassive necrosis (OR 5 4.3 [1.92-9.83], P < 0.001; OR 5 10.46 [2.7-40.5], P < 0.001). Cholestatic injury was associated with female gender and a CD4 of >200 cells/mm 3 , and submassive necrosis was associated with younger age. Hepatitis B demonstrated no association. Conclusion: In a high HIV burden area, drug-induced liver injury due to antiretroviral therapy and cotrimoxazole was a frequent clinicopathological finding; Mycobacterium tuberculosis was the leading opportunistic infection, with more than half of patients fulfilling criteria for tuberculosis immune reconstitution syndrome; liver biopsy remains a useful diagnostic procedure in this setting. (HEPATOLOGY 2015;61:1721-1729

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“…38–40 Among these baseline states, simulated mean CD4 varied from 380 (SD 190) cells/µL for those on ART to 560 (SD 230) cells/µL for those with acute infection (Table 2). 37,41,42 We assumed that individuals who are eligible for but not on ART at baseline would initiate therapy with a monthly probability of 15%, reflecting enhanced efforts to provide access to ART in the context of a trial. 13 …”

Section: Methodsmentioning

confidence: 99%

“… b CD4 distributions are truncated normal distributions calibrated to match data from references 41 (acute infection), 37 (undiagnosed, chronic), and 42 (off ART, first-line, and second-line). …”

Section: Figurementioning

confidence: 99%

The Impact of the 2013 WHO Antiretroviral Therapy Guidelines on the Feasibility of HIV Population Prevention Trials

Ross

Tanser

Pei

et al. 2014

HIV Clinical Trials

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Introduction Several cluster-randomized HIV prevention trials aim to demonstrate the population-level preventive impact of antiretroviral therapy (ART). 2013 World Health Organization guidelines raising the ART initiation threshold to CD4<500/µL could attenuate these trials’ effect size by increasing ART usage in control clusters. Methods We used a computational model to simulate strategies from a hypothetical cluster-randomized HIV prevention trial. The primary model outcome was the relative reduction in 24-month HIV incidence between control (ART offered with CD4 below threshold) and intervention (ART offered to all) strategies. We assessed this incidence reduction using the revised (CD4<500/µL) and prior (CD4<350/µL) control ART initiation thresholds. Additionally, we evaluated changes to trial characteristics that could bolster the incidence reduction. Results With a control ART initiation threshold of CD4<350/µL, 24-month HIV incidence under control and intervention strategies was 2.46/100PY and 1.96/100PY, a 21% reduction. Raising the threshold to CD4<500/µL decreased the incidence reduction by more than one-third, to 12%. Using this higher threshold, moving to a 36-month horizon (vs. 24-month), yearly control-strategy HIV screening (vs. biannual), and 2-monthly intervention-strategy screening (vs. biannual), resulted in a 31% incidence reduction, similar to effect size projections for ongoing trials. Alternate assumptions regarding cross-cluster contamination had the greatest influence on the incidence reduction. Conclusions Implementing the 2013 WHO HIV treatment threshold could substantially diminish the incidence reduction in HIV population prevention trials. Alternative HIV testing frequencies and trial horizons can bolster this incidence reduction, but could be logistically and ethically challenging. The feasibility of HIV population prevention trials should be reassessed as implementation of treatment guidelines evolves.

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Population-Based CD4 Counts in a Rural Area in South Africa with High HIV Prevalence and High Antiretroviral Treatment Coverage

Cited by 40 publications

References 47 publications

Time to eligibility for antiretroviral therapy in adults with CD4 cell count > 500 cells/μL in rural KwaZulu‐Natal, South Africa

Time to eligibility for antiretroviral therapy in adults with CD4 cell count > 500 cells/μL in rural KwaZulu‐Natal, South Africa

A clinicopathological cohort study of liver pathology in 301 patients with human immunodeficiency virus/acquired immune deficiency syndrome

The Impact of the 2013 WHO Antiretroviral Therapy Guidelines on the Feasibility of HIV Population Prevention Trials

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