Hepatitis C Drives Non-AIDS Event Rate in 320 HIV Controllers

Hepatitis C (HCV) infection proved to be the prime driver of non-AIDS events in a prospective study of 320 HIV patients in Spain who maintained a low or undetectable viral load without antiretroviral therapy. Despite this, hepatic disease accounted for less than one-third of non-AIDS illnesses in this group. Non-AIDS event incidence in HIV controllers was half that in a comparison group of HIV-infected noncontrollers: 1.252 versus 2.481 per 100 person-years. The study was published in the May 15 issue of Clinical Infectious Diseases.

A handful of people infected with HIV maintain a low or undetectable viral load without antiretroviral therapy. Although some experts consider HIV controllers a model of functional HIV cure, little is known about incidence of non-AIDS events and risk factors for these events in this group. To address those questions, researchers working with the Spanish ECRIS cohort conducted this prospective comparison with noncontrollers.

Controllers came from the Spanish AIDS Research Network HIV Controllers Cohort (ECRIS) group, a multicenter cohort that began in 2013. This analysis focused on 320 ECRIS members with a viral load below 2000 copies/mL for at least one year without antiretroviral therapy and with data on non-AIDS events. The study group included 138 elite controllers who kept their viral load below 50 copies/mL and 182 viremic controllers who maintained a viral load between 50 and 2000 copies/mL. The researchers also calculated non-AIDS event rates during the period of viral control and after loss of control (>2000 copies/mL). For comparison, the ECRIS team recruited a group of 632 HIV-infected noncontrollers who consecutively visited a single center in Spain.

Controllers were slightly older than noncontrollers (median 45 versus 44 years, P = .104) and included a significantly lower proportion of men (63.4% versus 79.9%, P < .001) and a significantly higher proportion with HCV infection (47.9% versus 30.4%, P < .001). The groups did not differ significantly in proportion of injection drug users. Compared with noncontrollers, controllers had a longer time since HIV diagnosis (median 17 versus 11 years, P < .001) and a higher nadir CD4 count (427 versus 177 cells/mm3, P < .001).

During follow-up, 65 controllers experienced 84 non-AIDS events for a crude incidence of 1.252 per 100 person-years (95% confidence interval [CI] 0.974 to 1.586). In contrast, 198 noncontrollers had 252 non-AIDS events for a crude incidence of 2.481 per 100 person-years (95% CI 2.153 to 2.845), a rate significantly higher than in controllers (P < .001). Non-AIDS event incidence did not differ substantially between elite controllers and viremic controllers.

Among controllers, the most frequent non-AIDS events were hepatic diseases (31%), bacterial pneumonia (21.4%) and malignancies (19%). Among noncontrollers, the most frequent events were bacterial pneumonia (32.9%) and cardiovascular disease (15.9%). Compared with noncontrollers, controllers had a lower incidence of cardiovascular disease, metabolic disease, bacterial pneumonia, renal disease and osteonecrosis, but not hepatic disease.

During a median 13.8 years of viral control, controllers had 65 non-AIDS events. During a median 5.37 years in which they had lost control, they experienced 16 non-AIDS events. Crude incidence of non-AIDS events did not differ significantly during the control period and the lost-control period. Hepatic events proved most prevalent in both periods (32.3% and 29.4%), while cardiovascular disease prevalence was lower during control than during lost control (10.8% versus 23.5%).

During the entire follow-up period, adjusted analysis identified two independent predictors of non-AIDS events: time of follow-up (odds ratio [OR] 1.068 per year, 95% CI 1.013 to 1.118, P = .007) and HCV infection (OR 3.361, 95% CI 1.495 to 7.556, P = .002). HCV infection also predicted non-AIDS events in the viral control period (OR 4.044, 95% CI 1.213 to 13.484, P = .023) and tended to predict events in the lost-control period (OR 3.774, 95% CI 0.934 to 15.259, P = .062).

The researchers note that the association between HCV infection and non-AIDS events -- even though hepatic disease represented only 31% of such events -- suggests that HCV causes extrahepatic damage that contributes to nonhepatic disease. They observe that HCV and HIV have synergistic effects on immunopathogenesis and that [[HCV has extrahepatic effects in people with and without HIV infection http://www.ncbi.nlm.nih.gov/pubmed/26132342]]. Eradication of HCV, they propose, "may ameliorate the presence of comorbidities" in HIV controllers. The authors also stress "the transitory nature of HIV control," as 143 of 320 cohort members (45%) lost control during follow-up.