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


Authors

Bisson GP, Ramchandani R, Miyahara S, Mngqibisa R, Matoga M, Ngongondo M, Samaneka W, Koech L, Naidoo K, Rassool M, Kirui F, Banda P, Mave V, Kadam D, Leger P, Henostroza G, Manabe YC, Bao J, Kumwenda J, Gupta A, Hosseinipour MC; Adult AIDS Clinical Trials Group A5274 (REMEMBER) Study Team.


Journal

AIDS. 2017 Jul 24. doi: 10.1097/QAD.0000000000001606. [Epub ahead of print]


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/mm 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/mm 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/mm and -2.7 vs. -2.7 log10 copies/mL, respectively. Each 20 cell/mm 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.

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