Ten years of antiretroviral therapy: Incidences, patterns and risk factors of opportunistic infections in an urban Ugandan cohort

Abstract

BackgroundDespite increased antiretroviral therapy (ART) coverage and the raised CD4 threshold for starting ART, opportunistic infections (OIs) are still one of the leading causes of death in sub-Saharan Africa. There are few studies from resource-limited settings on long-term reporting of OIs other than tuberculosis.MethodsPatients starting ART between April 2004 and April 2005 were enrolled and followed-up for 10 years in Kampala, Uganda. We report incidences, patterns and risk factors using Cox proportional hazards models of OIs among all patients and among patients with CD4 cell counts >200 cells/μL.ResultsOf the 559 patients starting ART, 164 patients developed a total of 241 OIs during 10 years of follow-up. The overall incidence was highest for oral candidiasis (25.4, 95% confidence interval (CI): 20.5–31.6 per 1000 person-years of follow-up), followed by tuberculosis (15.3, 95% CI: 11.7–20.1), herpes zoster (12.3, 95% CI: 9.1–16.6) and cryptococcal meningitis (3.0, 95% CI: 1.7–5.5). Incidence rates for all OIs were highest in the first year after ART initiation and decreased with the increase of the current CD4 cell count. Factors independently associated with development of OIs were baseline nevirapine-based regimens, time-varying higher viral load, time-varying lower CD4 cell count and time-varying lower hemoglobin. In patients developing OIs at a current CD4 cell count >200 cells/μL, factors independently associated with OI development were time-varying increase in viral load and time-varying decrease in hemoglobin, whereas a baseline CD4 cell count <50 cells/μL was protective.ConclusionWe report high early incidences of OIs, decreasing with increasing CD4 cell count and time spent on ART. Ongoing HIV replication and anemia were strong predictors for OI development independent of the CD4 cell count. Our findings support the recommendation for early initiation of ART and suggest close monitoring for OIs among patients recently started on ART, with low CD4 cell count, high viral load and anemia.

Incidence of common opportunistic infections among HIV-infected children on ART at Debre Markos referral hospital, Northwest Ethiopia: a retrospective cohort study

“…HIV-infected children with CD4 count or % below the threshold at the time of ART initiation were more likely to develop OIs as compared to those children with CD4 counts or % above the threshold). A 10 year retrospective study conducted in Uganda [40] documented that the occurrence of OIs in patients with lower CD4 cell counts at ART start was significantly high. Similar studies conducted in India [32,36], Latin America [29,30,41], and Asia [21] showed that low CD4 counts during ART enrollment significantly increased the risk of developing OIs.…”

Aberrant natural killer (NK) cell activation and dysfunction among ART-treated HIV-infected adults in an African cohort

“…In mouse models with T-cell deficiencies, NK cells conferred protection against Mtb infection [ 16 ]. Therefore persistent NK cell activation and dysfunction observed among ART-treated adults in sub-Saharan Africa, where Mycobacterium tuberculosis infection is endemic, presents a potential mechanism for the persistently high levels of active tuberculosis in our HIV treatment cohort [ 20 , 34 ].…”

“…Incomplete recovery of NK cell repertoire could contribute to the persistent T-cell function abnormalities previously described in our cohort of ART-treated adults, even when CD4 counts were restored to levels above 500 cells/μl [ 18 ]. With emerging evidence that NK cell function is key to protection against progression from latent Mtb infections to active tuberculosis, understanding recovery of NK cell function during ART is essential to the control of Mtb infection among ART-treated HIV-infected adults in sub-Saharan Africa where Tb remains a leading opportunistic infection and a leading cause of death [ 19 , 20 ].…”

Differences in human immunodeficiency virus-1C viral load and drug resistance mutation between plasma and cerebrospinal fluid in patients with human immunodeficiency virus-associated cryptococcal meningitis in Botswana

“…Successful roll-out of antiretroviral therapy (ART) has significantly reduced morbidity, mortality and incidence of opportunistic infections associated with Human Immunodeficiency Virus (HIV) infection and acquired immune deficiency syndrome. [ 1 ] However, Sub-Saharan Africa continues to be disproportionately burdened by the HIV-1 epidemic and the region has the greatest number of deaths, morbidity, and opportunistic infections. [ 2 ] One of the major biological barriers to complete eradication of HIV-1 is the ability of the virus to compartmentalise in reservoir sites such as the central nervous system (CNS), lymphoid tissue, gut tissues, and other anatomical sites.…”