Hepatitis C Increases Risk of Some Nonliver Diseases in People With HIV

Hepatitis C (HCV) infection independently raised the risk of kidney disease and osteoporosis or fracture in a Swiss HIV Cohort Study (SHCS) analysis of 5000 people with HIV. Among people treated for HCV infection, failure to achieve sustained virologic response (SVR) raised the diabetes risk 50%.

Because HIV and HCV share risk factors and infection routes, HCV prevalence reaches up to 30% in some HIV populations. HCV clearly heightens the risk of liver-related morbidity and mortality in people with HIV, but its impact on nonliver events and death remains incompletely understood. Studies hint, though, that HCV cure in HCV/HIV-coinfected people lowers nonliver mortality.

To explore these issues, SHCS investigators conducted two morbidity and mortality comparisons in their HIV cohort: (1) HCV-positive versus HCV-negative cohort members and (2) HCV-viremic versus successfully treated nonviremic (SVR) individuals. SHCS members make study visits every six months to complete surveys, give samples and get examined. All members receive HCV-antibody screening at cohort entry then every one or two years, depending on risk. Starting in 2002, HCV-positive people had quantitative HCV RNA measurements.

Related: Why HIV/HCV Coinfection May No Longer Be "Special"

The HCV analysis involved SHCS participants with at least one study visit and HCV-antibody results between August 1994 and December 2014. For each HCV-positive participant, the researchers matched an HCV-negative person for dates of cohort entry and last visit. The investigators used Poisson regression to explore associations between HCV status and clinical events (liver- and nonliver-related morbidities and mortality).

The analysis involved 2503 HCV-positive cases and 2503 matched HCV-negative controls. The HCV-positive group included 540 people with spontaneous HCV clearance, 1294 with untreated HCV, 345 treated people with SVR and 281 treated people without SVR. Only 10% of HCV regimens included direct-acting antivirals. Compared with HCV-negative people, those with HCV were more likely to be women (33.7% versus 21.6%), to have acquired HIV while injecting drugs (68.3% versus 2.3%), to be active drug injectors (12.7% versus 0.4%), to have had HIV longer (median 18.5 versus 16.2 years), to be current smokers (74.1% versus 37.2%) and to be heavy alcohol drinkers (13.7% versus 6.2%) (P ≤ .001 for all comparisons).

Through a median 8.2 years of follow-up, numbers of events in the 2503 HCV-positive and 2503 HCV-negative participants were, respectively, 107 and 18 liver events, 41 and 14 kidney events, 230 and 121 osteoporosis or fracture events, 82 and 94 diabetes cases, 114 and 129 cardiovascular events, 119 and 147 non-AIDS malignancies, 162 and 126 HIV Centers for Disease Control and Prevention (CDC) B/C events, 106 and 10 liver-related deaths and 227 and 218 nonliver-related deaths.

Comparing HCV-positive participants with HCV-negative participants, regression analysis determined that people with HCV had an independently higher risk of liver disease (adjusted incidence rate ratio [aIRR] 6.29, 95% confidence interval [CI] 3.52 to 11.22), liver-related death (aIRR 8.24, 95% CI 3.61 to 18.83), kidney disease (aIRR 2.43, 95% CI 1.11 to 5.33) and osteoporosis/fracture (aIRR 1.43, 95% CI 1.03 to 2.01).

Compared with people who achieved SVR, those who did not had a higher risk of liver events (aIRR 6.79, 95% CI 2.33 to 19.81), liver-related death (aIRR 3.29, 95% CI 1.35 to 8.05) and diabetes mellitus (aIRR 4.62, 95% CI 1.53 to 13.96). Compared with HCV-negative cohort members, HCV-treated people who did not attain SVR had the highest incidence of liver disease, liver-related death, kidney disease, diabetes mellitus and HIV CDC B/C events. SVR yielded a seven-fold reduction in liver-related events and a three-fold drop in liver-related deaths.

The SHCS team concludes that HCV exposure (but not HCV replication) is associated with a higher risk of kidney disease and osteoporosis in people with HIV. Among HCV-treated people with HIV, failure to achieve SVR boosted the risk of diabetes. Thus, diabetes was the only nonliver disease associated with HCV replication.