Oversight Committee for the Evaluation of Metabolic Complications of HAART, with representatives from academia, patient community, US Food and Drug Administration, European Medicines Agency and consortium of AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, ViiV Healthcare, Merck, Pfizer, F Hoffmann-La Roche, and Janssen Pharmaceuticals.

Background Mortality among HIV‐infected persons is decreasing, and causes of death are changing. Classification of deaths is hampered because of low autopsy rates, frequent deaths outside of hospitals, and shortcomings of International Statistical Classification of Diseases and Related Health Problems (ICD‐10) coding. Methods We studied mortality among Swiss HIV Cohort Study (SHCS) participants (1988–2010) and causes of death using the Coding Causes of Death in HIV (CoDe) protocol (2005–2009). Furthermore, we linked the SHCS data to the Swiss National Cohort (SNC) cause of death registry. Results AIDS‐related mortality peaked in 1992 [11.0/100 person‐years (PY)] and decreased to 0.144/100 PY (2006); non‐AIDS‐related mortality ranged between 1.74 (1993) and 0.776/100 PY (2006); mortality of unknown cause ranged between 2.33 and 0.206/100 PY. From 2005 to 2009, 459 of 9053 participants (5.1%) died. Underlying causes of deaths were: non‐AIDS malignancies [total, 85 (19%) of 446 deceased persons with known hepatitis C virus (HCV) status; HCV‐negative persons, 59 (24%); HCV‐coinfected persons, 26 (13%)]; AIDS [73 (16%); 50 (21%); 23 (11%)]; liver failure [67 (15%); 12 (5%); 55 (27%)]; non‐AIDS infections [42 (9%); 13 (5%); 29 (14%)]; substance use [31 (7%); 9 (4%); 22 (11%)]; suicide [28 (6%); 17 (7%), 11 (6%)]; myocardial infarction [28 (6%); 24 (10%), 4 (2%)]. Characteristics of deceased persons differed in 2005 vs. 2009: median age (45 vs. 49 years, respectively); median CD4 count (257 vs. 321 cells/μL, respectively); the percentage of individuals who were antiretroviral therapy‐naïve (13 vs. 5%, respectively); the percentage of deaths that were AIDS‐related (23 vs. 9%, respectively); and the percentage of deaths from non‐AIDS‐related malignancies (13 vs. 24%, respectively). Concordance in the classification of deaths was 72% between CoDe and ICD‐10 coding in the SHCS; and 60% between the SHCS and the SNC registry. Conclusions Mortality in HIV‐positive persons decreased to 1.33/100 PY in 2010. Hepatitis B or C virus coinfections increased the risk of death. Between 2005 and 2009, 84% of deaths were non‐AIDS‐related. Causes of deaths varied according to data source and coding system.

Non-AIDS events were common in the combination antiretroviral therapy era and associated with considerably mortality. Evidence on the impact of modifying immunodeficiency and lifestyle-related factors on the risk of non-AIDS events in HIV-infected persons is an important but unmet research need.

Objectives Among patients with HIV, the risk of death associated with different AIDS events has been quantified, but the risk of death associated with non-AIDS events has not been examined. We compared the risk of all-cause mortality following AIDS versus serious non-AIDS (SNA) events in SMART and ESPRIT. Design Data from 9,583 HIV-infected participants, 5,472 with CD4+ >350 cells/mm3 enrolled in SMART and 4,111 with CD4+ ≥300 cells/mm3 enrolled in ESPRIT were analyzed. Methods Cumulative mortality 6 months after AIDS and SNA (cardiovascular, renal, hepatic disease and malignancies) was estimated using the Kaplan-Meier method. Cox models were used to estimate hazard ratios (HRs) associated with AIDS and SNA on the risk of death overall and by treatment group within study. Results AIDS and SNA occurred in 286 and 435 participants with 47 (16%) and 115 (26%) subsequent deaths, respectively. Six-month cumulative mortality was 4.7% (95%CI:2.8–8.0) after experiencing an AIDS event and 13.4% (95%CI:10.5–17.0) after experiencing an SNA event. The adjusted HR for all-cause mortality for those who experienced AIDS versus those who did not was 4.9 (95%CI:3.6–6.8). The corresponding HR for SNA was 11.4 (95%CI:9.0–14.5) (p<0.001 for difference in HRs). Findings were similar for both treatment groups in SMART and both treatment groups in ESPRIT. Conclusions Among HIV-infected persons with higher CD4+ counts, SNA events occur more frequently and are associated with a greater risk of death than AIDS events. Future research should be aimed at comparing strategies to reduce morbidity and mortality associated with SNA events for HIV-infected persons.

Conclusions: A shortage of resources is evident, with an impact on HIV care inevitable. We need to prepare to operate with minimal medical resources, with the aim of securing constant supplies of ART. Nongovernmental organizations should re-evaluate their earlier objectives and support efforts to ensure continuity of ART delivery.