Purpose: Effective antiretroviral therapy (ART) improves survival in HIV-infected patients; however, the optimal management of multi-drug resistant (MDR) HIV in treatment-experienced patients with limited retreatment options remains uncertain. We evaluated whether ART interruption and/or intensification improved health-related quality of life (HRQoL). We also assessed the relationship between clinical characteristics and HRQoL.
Methods: Options in Management with Antiretrovirals (OPTIMA) randomized 368 patients to an intended 12 week ART interruption, mega-ART (≥ 5 drugs), both strategies, or standard ART (≤ 4 drugs). HRQoL was assessed with the Medical Outcomes Study HIV physical (PHS) and mental (MHS) health summary scores, the Health Utilities Index Mark 3 (HUI3), EQ-5D, visual analog scale (VAS), standard gamble (SG), and time trade-off (TTO) at baseline, 6 weeks, 12 weeks, and every 12 weeks thereafter. Length of follow-up ranged between 1.5 and 6.25 years. Controlling for baseline values, we used random effects models to estimate the effect of treatment group assignment on HRQoL over time, as well as the effect of severe AIDS events (ADEs), log HIV viral load (vL), death within 90 days, CD4 levels, and ongoing and cumulative serious adverse events (SAEs) on HRQoL.
Results: There were no sustained significant differences in HRQoL between management arms. For those randomized to ART interruption, HRQoL decreased during the first 12 weeks of the trial, according to HUI3 (-0.029, ns), EQ-5D (-0.014, ns), SG (0.041, ns), TTO (-0.031, ns), VAS (-5.715, p<.0001), PHS (-2.731, p<.0001), and MHS (-1.388, p<.05). Separate models found significantly lower HRQoL associated with higher viral loads (-.012, p<.0001), death within 90 days (-.116, p<.0001), CD4+ count less than 50 (-.042, p<.001), CD4+ count between 50 and 100 (-.022, p<.05), at least 1 ongoing SAE (-.076, p<.0001), and either one or two or more prior SAEs (-.029, p<.01; -.065, p<.0001) (HUI3 model results reported).
Conclusion: There were no sustained HRQoL differences among MDR-HIV infected patients randomized to ART interruption and/or intensification. Contrary to expectation, the HRQoL of those randomized to interruption, as measured by VAS, PHS, and MHS, significantly decreased during the first 12 weeks after trial enrollment. Most instruments were sensitive to significant and clinically meaningful changes in health, with higher viral loads, approaching death, low CD4 levels, and ongoing and cumulative SAEs all associated with lower HRQoL scores.
Candidate for the Lee B. Lusted Student Prize Competition