Risk factors for early mortality on antiretroviral therapy in advanced HIV-infected adults

Abstract

Summary Background Many HIV-infected individuals present with advanced HIV disease. These patients are at high risk of death after antiretroviral therapy (ART) initiation, but risk factors for death in these patients are unclear. Methods We used data from a multi-site randomized trial comparing empiric versus preventive TB therapy in HIV-infected adults initiating ART with CD4 counts <50 cells/mm3 to evaluate risk factors for death within 48 weeks after ART initiation. Cox proportional hazards models were fit to evaluate characteristics present at baseline and at 4 weeks after ART initiation, including the week 4 CD4 cell response and new opportunistic infections (OIs). Findings Of 850 enrolled, the median pre-ART CD4 count was 18 cells/mm3 and 67 (7.9%) died. Baseline risk factors for death included lymphadenopathy, lower CD4 count, lower serum albumin, high white blood cell (WBC) count, elevated neutrophil percent, and lower hemoglobin. Among 746 participants with data at week 4, the median changes in CD4 count and viral load for those who died (n=43) vs. survived were 26 vs. 56 cells/mm3 and −2.7 vs. −2.7 log10 copies/mL, respectively. Each 20 cell/mm3 lower change in week 4 CD4 count was associated with a 20% increased risk of post week-4 mortality (adj. HR 1.20, 1.01–1.42, p=.038). Interpretation Evidence of active infection and sub-optimal immunologic response during the first month of ART are associated with death in the first year after ART initiation in those with advanced HIV disease taking TB preventative therapy. Strategies to reduce early mortality in this population warrant further investigation.

The Persistent Challenge of Advanced HIV Disease and AIDS in the Era of Antiretroviral Therapy

“…The second study from South Africa further highlights a relatively new understanding, that an increasing proportion of people with very advanced HIV disease are ART experienced, and in this study increased from 14.3% in 2008 to 56.7% in 2017 [ 2 ]. Again, men were at greater risk [ 2 ], a finding reported by other studies [ 4 , 5 ]. These findings are supported by a study from Kenya and the Democratic Republic of Congo (DRC) using data from inpatient departments in Médecins Sans Frontières–supported hospital wards [ 3 ], which found that the majority of HIV-infected hospitalized patients in both sites were ART experienced.…”

Distribution of advanced HIV disease from three high HIV prevalence settings in Sub-Saharan Africa: a secondary analysis data from three population-based cross-sectional surveys in Eshowe (South Africa), Ndhiwa (Kenya) and Chiradzulu (Malawi)

“…We compared the cascade of care (from diagnosis (those who knew they were HIV-positive), to those on ART, to virologically suppressed) for all individuals with advanced HIV disease stratified by country and sex using chi-square tests. As the risk of mortality and morbidity increases with decreasing CD4 cell count [4][5][6], we also evaluated the cascade of care only among individuals with CD4 < 100 cells/µl. Among those on ART, we further examined the distribution of advanced HIV by duration on ART, categorized as <6 months or ≥6 months on ART.…”

“…About 940,000 HIV-related deaths occurred globally in 2017 and about 70% of these were from sub-Saharan Africa [3]. Mortality is very high among individuals with advanced HIV disease particularly those with very low CD4 count [4][5][6][7].…”

Late Presentation With HIV in Africa: Phenotypes, Risk, and Risk Stratification in the REALITY Trial

“…A recent analysis of 850 HIV-infected adults/adolescents initiating ART with CD4 count <50 cells/µL, randomized to receive empiric tuberculosis treatment or isoniazid preventive therapy, identified higher mortality in those with lower CD4 cell count, albumin, and hemoglobin; higher white blood cell (WBC) count or neutrophil percentage; or lymphadenopathy [ 10 ]. Given the substantial numbers presenting with low CD4 cell count and their high mortality shortly after ART initiation, additional studies in “late presenters” are important to identify their key characteristics, particularly if baseline CD4 count testing is not always available, to identify them earlier at healthcare facilities and prioritize them for additional interventions.…”