Causes of Death in HIV‐1–Infected Patients Treated with Antiretroviral Therapy, 1996–2006: Collaborative Analysis of 13 HIV Cohort Studies

Abstract

Background We examined specific causes of mortality in human immunodeficiency virus type 1 (HIV-1)–infected patients who initiated antiretroviral therapy (ART) in Europe and North America from 1996 through 2006, and we quantified associations of prognostic factors with cause-specific mortality. Methods We retrospectively classified all deaths among 39,272 patients enrolled in 13 HIV-1 cohorts (154,667 person years of follow-up) into the categories specified in the Cause of Death (CoDe) project protocol. Results In 1597 (85%) of 1876 deaths, a definitive cause of death could be assigned. Among these, 792 deaths (49.5%) were AIDS related, followed by non-AIDS malignancies (189; 11.8%), non-AIDS infections (131; 8.2%), violence- and/or drug-related causes (124; 7.7%), liver disease (113; 7.0%), and cardiovascular disease (103; 6.5%). Rates of AIDS-related death (hazard ratio [HR] per 100 cell decrease, 1.43; 95% confidence interval [CI], 1.34–1.53) and death from renal failure (HR, 1.73; 95% CI, 1.18–2.55) were strongly inversely related to CD4 count at initiation of ART, whereas rates of death attributable to AIDS (HR for viral load >5 vs ≤5 log copies/mL, 1.31; 95% CI, 1.12–1.53), infection (HR, 1.85; 95% CI, 1.25–2.73), cardiovascular (HR, 1.54; 95% CI, 1.05–2.27), and respiratory causes (HR, 3.62; 95% CI, 1.30–10.09) were higher in patients with baseline viral load >5 log copies/mL than in other patients. Rates of each cause of death were higher in patients with presumed transmission via injection drug use than in other patients, with marked increases in rates of liver-related (HR for injection drug use vs non–injection drug use, 6.06; 95% CI, 4.03–9.09) and respiratory tract–related (HR, 4.94; 95% CI, 1.96–12.45) mortality. The proportion of deaths classified as AIDS related decreased with increasing duration of ART. Conclusions Important contributors to non-AIDS mortality in treated HIV-1–infected individuals must be addressed if decreases in mortality rates are to continue.

Increased non‐AIDS mortality among persons with AIDS‐defining events after antiretroviral therapy initiation

“…Otherwise, two clinicians independently classified each death. Disagreements between clinicians and/or computer‐classifications were resolved via panel discussion as per the CoDe protocol 1, 31.…”

“…In the era of antiretroviral therapy (ART), there have been striking decreases in acquired immune deficiency syndrome (AIDS)‐related mortality 1, 2, 3 and prolongation of life expectancy 4, 5, 6, 7 for people living with HIV infection (PLWH). With this, there has been a shift in distribution of causes of death toward non‐AIDS‐defining events (NADEs) 8, 9, 10, 11, 12.…”

Misdiagnosed HIV infection in pregnant women initiating universal ART in South Africa

“…In addition to their comparable performance with the gold standard enzyme-linked immunosorbent assay (ELISA), RDTs are inexpensive, are easy to use and can be used at point-of-care. With recent evidence and recommendations favouring early antiretroviral treatment (ART) initiation [2–4] and the universal “test-and-start” approach [5], the use of RDTs to quickly diagnose HIV infection and facilitate immediate ART initiation will be critical in achieving the UNAIDS 90-90-90 goal in many low- and middle-income countries (LMIC).…”

Causes of Deaths of HIV Infected Patients at the HIV/AIDS Center of Excellence of the University of Lubumbashi in Lubumbashi, Democratic Republic of Congo

“…Causes of death are dominated by opportunistic infections (OI) in powers countries and by cardiovascular diseases, viral hepatitis and cancers in the industrialized countries [3,4].…”