Risk of all-cause mortality associated with nonfatal AIDS and serious non-AIDS events among adults infected with HIV

Abstract

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 the Strategies for Management of Antiretroviral Therapy (SMART) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT).

Design: Data from 9583 HIV-infected participants, 5472 with a CD4 cell count more than 350 cells/microl enrolled in SMART and 4111 with a CD4 cell count 300 cells/microl or more enrolled in ESPRIT, were analyzed.

Methods: Cumulative mortality 6 months after AIDS and SNA events (cardiovascular, renal, hepatic disease, and malignancies) was estimated using the Kaplan-Meier method. Cox models were used to estimate hazard ratios associated with AIDS and SNA events on the risk of death overall and by treatment group within study.

Results: AIDS and SNA events occurred in 286 and 435 participants with 47 (16%) and 115 (26%) subsequent deaths, respectively. Six-month cumulative mortality was 4.7% [95% confidence interval (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 hazard ratio 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 hazard ratio for SNA was 11.4 (95% CI 9.0-14.5) (P < 0.001 for difference in hazard ratios). Findings were similar for both treatment groups in SMART and both treatment groups in ESPRIT.

Conclusion: Among HIV-infected persons with higher CD4 cell 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.

Figure 1

Time from AIDS or SNA event to death. SMART and ESPRIT combined.

Figure 2

Figure 2a. Adjusted* hazard ratios for death associated with AIDS events during follow-up. Interaction p-values across treatment groups for SMART, ESPRIT and combined are 0.77, 0.57, 0.93 respectively. Figure 2b. Adjusted* hazard ratios for death associated with SNA events during follow-up. Interaction p-values across treatment groups for SMART, ESPRIT and combined are 0.49, 0.10, 0.25 respectively. *Adjusted for age, gender, black race, baseline CD4, baseline HIV-RNA (> 500 copies), nadir CD4, and latest CD4 and HIV-RNA (> 500 copies) †Deaths occurring after AIDS event ‡Stratified by treatment group and study

Figure 2

Figure 2a. Adjusted* hazard ratios for death associated with AIDS events during follow-up. Interaction p-values across treatment groups for SMART, ESPRIT and combined are 0.77, 0.57, 0.93 respectively. Figure 2b. Adjusted* hazard ratios for death associated with SNA events during follow-up. Interaction p-values across treatment groups for SMART, ESPRIT and combined are 0.49, 0.10, 0.25 respectively. *Adjusted for age, gender, black race, baseline CD4, baseline HIV-RNA (> 500 copies), nadir CD4, and latest CD4 and HIV-RNA (> 500 copies) †Deaths occurring after AIDS event ‡Stratified by treatment group and study

Figure 3

Adjusted* hazard ratios† for death associated with types of AIDS and SNA events during follow-up. SMART and ESPRIT combined. *Adjusted for age, gender, black race, baseline CD4, baseline HIV-RNA (> 500 copies), nadir CD4, and latest CD4 and HIV-RNA (> 500 copies) †Stratified by treatment group and study ‡Deaths occurring after AIDS or SNA event