Effect of statin therapy in reducing the risk of serious non-AIDS-defining events and nonaccidental death.

BACKGROUND: Excessive inflammation persists despite antiretroviral treatment. Statins decrease cardiovascular (CV) disease risk by reducing low-density lipoprotein cholesterol and inflammation. We performed an exploratory analysis to evaluate whether statin therapy decreased risk of non-AIDS-defining events and nonaccidental death. METHODS: A total of 3601 subjects not on a statin from the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort were included. Outcome was time to first clinical event (CV event, renal or hepatic disease, incident diabetes, thrombotic/embolic event, nontraumatic fracture, non-AIDS-defining malignancy, serious bacterial infection, or nonaccidental death); event categories were also analyzed separately. Inverse probability of treatment and censoring weighted Cox proportional hazard models were used to assess the causal statin effect. Differential statin effects by baseline covariates were evaluated. RESULTS: Over 15 135 person-years (PY) of follow-up, 484 subjects initiated statins; 616 experienced an event (crude event rate, 4.4/100 PY on a statin and 4.1/100 PY not on a statin); the unadjusted hazard ratio (HR) was 1.17 (95% confidence interval [CI], .91-1.50). In a final weighted model, the adjusted HR (AHR) was 0.81 (95% CI, .53- 1.24). Results for other clinical events were similar, except for malignancies (AHR, 0.43 [95% CI, .19-.94]) and bacterial infections (AHR, 1.30 [95% CI, .64-2.65]). No differential statin effects by baseline covariates were detected. CONCLUSIONS: Although statin therapy was not associated with a reduction in time to all non-AIDS-defining event or nonaccidental death, it was associated with a statistically significant 57% reduction in non-AIDS-defining malignancies. Confirmatory studies are needed to evaluate statin-associated reduction in risk of cancer and non-AIDS-associated morbidities.

Incidence rate of and factors associated with loss to follow-up in a longitudinal cohort of antiretroviral-treated HIV-infected persons: an AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) analysis.

PURPOSE: Examine incidence and factors associated with loss to follow-up (LTFU) in the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) cohort. METHOD: ALLRT is a prospective cohort of HIV-infected persons randomized to antiretroviral (ARV) regimens/strategies in ACTG trials and followed long-term after the trial ends. Person-years were calculated from ALLRT entry until loss to follow-up (LTFU; defined using off-study reasons or ≥ 3 consecutive missed visits), death/ severe debilitation/site closures, or June 2009 (censored). Poisson regression was used to examine LTFU factors separately among participants who were ARV naïve or ARV experienced at trial entry. RESULTS: Among 4,630 participants (22,524 person-years), 1,140 were lost to follow-up, 237 died, 29 were severely debilitated, and 443 were at sites that closed. The LTFU incidence was 5.5 and 4.2 per 100 person-years among previously ARV-naïve and ARV-experienced participants, respectively. In both groups, age ≤ 50, site location, being off ARVs, and viral load ≥ 400 copies/mL were associated with a higher risk of LTFU. Among ARV-naïve participants, male sex, education <16 years, intravenous drug use, and cigarette smoking were also associated with LTFU. CONCLUSION: Knowledge of differential LTFU can help researchers identify participants at risk of LTFU in longitudinal HIV cohorts and design retention strategies, thereby limiting study bias. The identified factors should be included in inverse probability of weighting models to account for LTFU.

The impact of HIV/HCV co-infection on health care utilization and disability: results of the ACTG Longitudinal Linked Randomized Trials (ALLRT) Cohort.

HIV/hepatitis C virus (HCV) co-infection places a growing burden on the HIV/AIDS care delivery system. Evidence-based estimates of health services utilization among HIV/HCV co-infected patients can inform efficient planning. We analyzed data from the ACTG Longitudinal Linked Randomized Trials (ALLRT) cohort to estimate resource utilization and disability among HIV/HCV co-infected patients and compare them to rates seen in HIV mono-infected patients. The analysis included HIV-infected subjects enrolled in the ALLRT cohort between 2000 and 2007 who had at least one CD4 count measured and completed at least one resource utilization data collection form (N = 3143). Primary outcomes included the relative risk of hospital nights, emergency department (ED) visits, and disability days for HIV/HCV co-infected vs HIV mono-infected subjects. When controlling for age, sex, race, history of AIDS-defining events, current CD4 count and current HIV RNA, the relative risk of hospitalization, ED visits, and disability days for subjects with HIV/HCV co-infection compared to those with HIV mono-infection were 1.8 (95% CI: 1.3-2.5), 1.7 (95% CI: 1.4-2.1), and 1.6 (95% CI: 1.3-1.9) respectively. Programs serving HIV/HCV co-infected patients can expect approximately 70% higher rates of utilization than expected from a similar cohort of HIV mono-infected patients.

Effects of active HCV replication on neurologic status in HIV RNA virally suppressed patients.

BACKGROUND: Hepatitis C virus (HCV) is a frequent copathogen with HIV. Both viruses appear to replicate in the brain and both are implicated in neurocognitive and peripheral neuropathy syndromes. Interaction of the viruses is likely to be complicated and better understanding of the contributions of each virus will be necessary to make evidence-based therapeutic decisions. METHODS: This study was designed to determine if active HCV infection, identified by quantitative HCV RNA determination, is associated with increased neurocognitive deficits or excess development of distal sensory peripheral neuropathy in HIV coinfected patients with stable HIV viral suppression. The AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) study was the source of subjects with known HIV treatment status, neurocognitive and neuropathy evaluations, and HCV status. Subjects were selected based on HCV antibody status (249 positive; 310 negative). RESULTS: HCV RNA viral loads were detectable in 172 participants with controlled HIV infection and available neurologic evaluations in the ALLRT. These participants were compared with 345 participants with undetectable HCV viral load and the same inclusion criteria from the same cohort. Neurocognitive performance measured by Trail-Making A or B and digit symbol testing was not dissimilar between the 2 groups. In addition, there was no significant association between active HCV replication and distal sensory neuropathy. CONCLUSION: Clinically significant neurocognitive dysfunction and peripheral neuropathy were not exacerbated by active hepatitis C virus infection in the setting of optimally treated HIV infection.