Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial

Abstract

SummaryBackgroundThe effects of antiretroviral therapy on risk of severe bacterial infections in people with high CD4 cell counts have not been well described. In this study, we aimed to quantify the effects of immediate versus deferred ART on the risk of severe bacterial infection in people with high CD4 cell counts in a preplanned analysis of the START trial.MethodsThe START trial was a randomised controlled trial in ART-naive HIV-positive patients with CD4 cell count of more than 500 cells per μL assigned to immediate ART or deferral until their CD4 cell counts were lower than 350 cells per μL. We used Cox proportional hazards regression to model time to severe bacterial infection, which was defined as a composite endpoint of bacterial pneumonia (confirmed by the endpoint review committee), pulmonary or extrapulmonary tuberculosis, or any bacterial infectious disorder of grade 4 severity, that required unscheduled hospital admissions, or caused death. This study is registered with ClinicalTrials.gov, number NCT00867048.FindingsPatients were recruited from April 15, 2009, to Dec 23, 2013. The data cutoff for follow-up was May 26, 2015. Of 4685 HIV-positive people enrolled, 120 had severe bacterial infections (immediate-initiation group n=34, deferred-initiation group n=86; median 2·8 years of follow-up). Immediate ART was associated with a reduced risk of severe bacterial infection compared with deferred ART (hazard ratio [HR] 0·39, 95% CI 0·26–0·57, p<0·0001). In the immediate-initiation group, average neutrophil count over follow-up was 321 cells per μL higher, and average CD4 cell count 194 cells per μL higher than the deferred-initiation group (p<0·0001). In univariable analysis, higher time-updated CD4 cell count (0·78, 0·71–0·85, p=0·0001) was associated with reduced risk of severe bacterial infection. Time-updated neutrophil count was not associated with severe bacterial infection. After adjustment for time-updated factors in multivariable analysis, particularly the CD4 cell count, the HR for immediate-initiation group moved closer to 1 (HR 0·84, 0·50–1·41, p=0·52). These results were consistent when subgroups of the severe bacterial infection composite were analysed separately.InterpretationImmediate ART reduces the risk of several severe bacterial infections in HIV-positive people with high CD4 cell count. This is partly explained by ART-induced increases in CD4 cell count, but not by increases in neutrophil count.FundingNational Institute of Allergy and Infectious Diseases National Institutes of Health, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales, Bundesministerium für Bildung und Forschung, European AIDS Treatment Network, Australian National Health and Medical Research Council, UK National Institute for Health Research and Medical Research Council, Danish National Research Foundation.

Early antiretroviral therapy and daily pre‐exposure prophylaxis for HIV prevention among female sex workers in Cotonou, Benin: a prospective observational demonstration study

“…Uptake of both E‐ART and PrEP was high, but HIV‐positive FSWs were more willing to participate in E‐ART than HIV‐negative FSWs were to participate in PrEP. This situation was predictable given the obvious need for treatment among HIV‐positive women . Observed retention rates were arguably low by the end of the study but did not differ between E‐ART and PrEP participants still living in Cotonou.…”

Low nadir CD4+ T-cell counts predict gut dysbiosis in HIV-1 infection

“…3,4 Up to one-third of all HIV-1-related deaths in Western countries can be attributed to late HIV-1 diagnosis. 5 Low nadir CD4+ T-cell counts are a major risk factor for developing AIDS-and non-AIDS-defining illnesses, [6][7][8] bacterial infections, 9 ART failure, 5 and suboptimal immune reconstitution with ART. 10,11 Premature aging involves the precocious development of type 2 diabetes, dyslipidemia, cardiovascular diseases, osteoporosis, and frailty syndrome.…”

Short-term outcomes of rapid initiation of antiretroviral therapy among HIV-positive patients: real-world experience from a single-centre retrospective cohort in Taiwan

“…The TEMPRANO and START studies have provided evidence that early initiation of combination antiretroviral therapy (cART) is associated with a more favourable prognosis; subsequently, the WHO recommended in 2015 that all patients be treated with cART once HIV infection is diagnosed 1–5. At the population level, starting antiretroviral therapy (ART) soon after HIV diagnosis can prevent onwards HIV transmission (‘treatment as prevention’),6 especially when high rates of incident sexually transmitted infections (STIs) are observed among patients diagnosed as having acute HIV infection, which are considered biomarkers of onwards transmission 7.…”