Strategies to reduce early morbidity and mortality in adults receiving antiretroviral therapy in resource-limited settings

Abstract

Purpose of review: We review recently published literature concerning early morbidity and mortality during antiretroviral therapy (ART) among patients in resource-limited settings. We focus on articles providing insights into this burden of disease and strategies to address it.

Recent findings: In sub-Saharan Africa, mortality rates during the first year of ART are very high (8-26%), with most deaths occurring in the first few months. This figure compares with 3-13% in programmes in Latin America and the Caribbean and 11-13% in south-east Asia. Risk factors generally reflect late presentation with advanced symptomatic disease. Key causes of morbidity and mortality include tuberculosis (TB), acute sepsis, cryptococcal meningitis, malignancy and wasting syndrome/chronic diarrhoea. Current literature shows that the fundamental need is for much earlier HIV diagnosis and initiation of ART. In addition, further studies provide data on the role of screening and prophylaxis against opportunistic diseases (particularly TB, bacterial sepsis and cryptococcal disease) and the management of specific opportunistic diseases and complications of ART. Effective and sustainable delivery of these interventions requires strengthening of programmes.

Summary: Strategies to address this disease burden should include earlier HIV diagnosis and ART initiation, screening and prophylaxis for opportunistic infections, optimized management of specific diseases and treatment complications, and programme strengthening.

Figure 1

Kaplan Meier plots comparing the cumulative mortality during ART in South African (Gugulethu and Khayelitsha) cohorts and the Swiss HIV Cohort Study. Baseline CD4 cell counts were 80 cells/μL and 204 cells/ μL, respectively. Graph reproduced from [10].

Figure 2

Graphs showing (a) mortality rates and (b) tuberculosis (TB) incidence rates (95% confidence intervals, deaths per 100 person-years) plotted against CD4 counts measured at baseline and updated every 4-months during ART (updated CD4 counts). As CD4 cell counts increased, the mortality rate is seen to fall very steeply. Above a CD4 count threshold of 200 cells/μL, however, no further significant reductions occurred with further CD4 cell count recovery. TB rates similarly decreased with increasing CD4 cell counts, but substantial rates persisted at CD4 counts of 200-500 cells/ μL but significantly decreased above a threshold of 500 cells/μL. Data adapted from [11**] and [12**].

Figure 3

Kaplan Meier plot showing the cumulative mortality in the Gugulethu cohort in groups of patients with baseline CD4 cell counts <100 cells/μL or >100 cells/μL from the time of enrolment into the programme (includes mortality accruing in one month pre-ART period plus mortality on ART). Data adapted from [11**].

Figure 4

Graph showing mortality after one year of ART for 21 cohorts plotted against the Gross Domestic Product (GDP) per capita (in US dollars) for the countries represented. Cohorts included are from countries in sub-Saharan Africa, Latin America and the Caribbean and South East Asia from references [5**, 6**, 8**, 18]. The countries from which the data are derived are indicated and some are represented by more than one cohort. Mortality risk is very heterogeneous, but cohorts in countries with lower GDP tend to be associated with higher mortality risk.

Figure 5

Graph showing changing tuberculosis (TB) incidence rate (95% confidence intervals, cases per 100 person-years) with increasing duration of antiretroviral therapy (ART) in a South African cohort. The incidence rate is extremely high in the first 3 months but rapidly decreases thereafter. Data adapted from [23, 12].