Incidence and risk factors for hepatotoxicity following antiretroviral initiation in patients attending Themba Lethu Clinic, Johannesburg

M.Sc. (Epidemiology), Faculty of Health Sciences, University of the Witwatersrand, 2011Background and Objectives The advent of Highly Active Antiretroviral Therapy (HAART) has resulted in a significant reduction in HIV/AIDS related morbidity and mortality in sub-Saharan Africa. However, toxicities due to HAART continue to pose challenges to the success of different regimens. Severe hepatotoxicity is one of the significant adverse events occurring in patients on HAART. Information on the incidence and risk factors for severe hepatotoxicity in cohorts from resource poor settings is limited. It is against this background that we undertook the study to determine the incidence and explore factors associated with severe hepatotoxicity following HAART initiation in a South African cohort. Materials and Methods Secondary data analysis of a prospective cohort 9764 HIV-infected adult patients initiated on HAART at the Themba Lethu clinic antiretroviral rollout facility in Johannesburg, South Africa between 1st April 2004 and 30th June 2009 was conducted. Severe hepatotoxicity cases were identified within the first 12 months of initiating HAART as grade 3 or 4 elevation in baseline ALT levels. The incidence rate of severe hepatotoxicity was calculated and potential socio-demographic and clinical predictors were explored using Cox proportional hazard regression modelling. Results At baseline, 91.8% of patients were commenced on an efavirenz-based regimen while only 8.2% were on a nevirapine-based regimen. The median CD4 count at v initiation of HAART for this cohort was 80 cells/ mm3, a figure lower than the Department of Health (DoH) CD4 cut off for initiating HAART of 200 cells/ mm3. The overall incidence rate of severe hepatotoxicity was 10.7 (95% CI: 8.7 – 13.1) cases per 1000 p-yrs of follow-up. The period with the highest risk of severe hepatotoxicity was within 2 months of initiating HAART. Incidence of severe hepatotoxicity was 21.1(95% CI: 12.7 – 34.9) cases per 1000 p-yrs among patients on a nevirapine-based regimen and 9.7 (95% CI: 7.8 – 12.1) cases per 1000 p-yrs in those on an efavirenz-based one. The hazard for severe hepatotoxicity within the first year of initiating HAART was 2.17 times higher in individuals on a nevirapine-based regimen compared to those on an efavirenz-based regimen after adjusting for baseline ALT, baseline CD4, age and gender (HR = 2.17; 95%CI = 1.18 – 3.97; p = 0.013). Though imprecise, the estimate for baseline ALT category suggested an increased risk for severe hepatotoxicity in individuals with a baseline ALT more than 40 I.U/L compared to those with a baseline ALT of less than 40 I.U/L (HR = 1.63; 95%CI = 1.00 – 2.67; p = 0.050). Conclusion The results of the study suggest that severe hepatotoxicity following initiation of HAART in this cohort is low compared to other previously studied cohorts. The high incidence rate of severe hepatotoxicity in the first two months of initiating HAART necessitates the need for more frequent and careful monitoring of ALT levels early during therapy. Patients on a nevirapine-based regimen have a higher risk of developing severe hepatotoxicity when compared to their counterparts on an efavirenz-based regimen, a result consistent with findings from previous studies

Piloting and evaluating family-centered HIV care in Eswatini

There are substantial gaps in essential services and numerous missed opportunities to engage children in care and provide effective HIV treatment. Although not new, family-centered care models that provide HIV services comprehensively to families as a unit, rather than providing separate services to children and adults, have the potential to address family needs and break down social, physical, and emotional barriers to accessing care. The family-centered care study (FAM-CARE) aims to contribute to our understanding of the role of family-centered care models (FCCM) in improving pediatric HIV outcomes in a sub-Saharan African setting

Voluntary Medical Male Circumcision for HIV Prevention in Swaziland: Modeling the Impact of Age Targeting.

BACKGROUND:Voluntary medical male circumcision (VMMC) for HIV prevention has been a priority for Swaziland since 2009. Initially focusing on men ages 15-49, the Ministry of Health reduced the minimum age for VMMC from 15 to 10 years in 2012, given the existing demand among 10- to 15-year-olds. To understand the implications of focusing VMMC service delivery on specific age groups, the MOH undertook a modeling exercise to inform policy and implementation in 2013-2014. METHODS AND FINDINGS:The impact and cost of circumcising specific age groups were assessed using the Decision Makers' Program Planning Tool, Version 2.0 (DMPPT 2.0), a simple compartmental model. We used age-specific HIV incidence from the Swaziland HIV Incidence Measurement Survey (SHIMS). Population, mortality, births, and HIV prevalence were imported from a national Spectrum/Goals model recently updated in consultation with country stakeholders. Baseline male circumcision prevalence was derived from the most recent Swaziland Demographic and Health Survey. The lowest numbers of VMMCs per HIV infection averted are achieved when males ages 15-19, 20-24, 25-29, and 30-34 are circumcised, although the uncertainty bounds for the estimates overlap. Circumcising males ages 25-29 and 20-24 provides the most immediate reduction in HIV incidence. Circumcising males ages 15-19, 20-24, and 25-29 provides the greatest magnitude incidence reduction within 15 years. The lowest cost per HIV infection averted is achieved by circumcising males ages 15-34: $870 U.S. dollars (USD). CONCLUSIONS:The potential impact, cost, and cost-effectiveness of VMMC scale-up in Swaziland are not uniform. They vary by the age group of males circumcised. Based on the results of this modeling exercise, the Ministry of Health's Swaziland Male Circumcision Strategic and Operational Plan 2014-2018 adopted an implementation strategy that calls for circumcision to be scaled up to 50% coverage for neonates, 80% among males ages 10-29, and 55% among males ages 30-34

Correction: Voluntary Medical Male Circumcision for HIV Prevention in Swaziland: Modeling the Impact of Age Targeting.

[This corrects the article DOI: 10.1371/journal.pone.0156776.]

Impact, Cost, and Cost-effectiveness of VMMC Scale-up Scenarios, 2014–2028.

<p>Impact, Cost, and Cost-effectiveness of VMMC Scale-up Scenarios, 2014–2028.</p

Swaziland Age-targeting Strategy Scenarios.

<p>Swaziland Age-targeting Strategy Scenarios.</p