Evaluation of the possible influence of hepatitis C virus and liver fibrosis on HIV type 1 immunological and virological outcomes

Abstract

ObjectivesThe aim of the study was to evaluate the possible effect of hepatitis C virus (HCV) coinfection on the viroimmunological outcomes of HIV-1 infection. MethodsA cross-sectional study of 805 patients with active HCV infection receiving or not receiving antiretroviral therapy (ART) was carried out. ResultsA number of parameters were significantly associated with undetectable HIV-1 viral load in univariate analyses, such as age, toxic habits, CD4 cell count, liver test results, HCV viral load and ART. However, only current ART (Po0.0001), CD4 cell count (Po0.0001), age (P 5 0.004) and current injecting drug use (P 5 0.02) were independently associated with undetectable viral load in multivariate analysis. None of the many HCV-and liver fibrosis-related parameters analysed showed a significant association with HIV-1 viral load or CD4 cell count in multivariate analyses, with the exception of the annual fibrosis progression index which almost reached statistical significance in the subgroup of ART-untreated patients (P 5 0.06) and was inversely predictive of CD4 cell count in the whole group (P 5 0.007). However, its relative weight was modest, as it only explained 0.8% of the total variability in CD4 cell count. ConclusionsHCV-related parameters did not significantly affect virological and immunological outcomes of HIV-1 infection in ART-treated and untreated patients. In contrast, liver fibrosis, as measured using the annual fibrosis progression index, was inversely associated with CD4 cell count, although its weight was relatively small. Therefore, HCV-and liver fibrosis-related factors do not seem appreciably to influence these outcomes from a practical viewpoint in ART-naïve patients, nor impair CD4 and HIV-1 viral load responses to ART.

Correlates of HIV sustained viral suppression in HIV/hepatitis C virus coinfected patients

“…In line with previous reports, we found that older age and better adherence to HIV therapy were associated with HIV SVS [11,17]. Furthermore, excessive alcohol consumption, which is a known predictor of poor adherence to HAART, was associated with failure to achieve HIV SVS in our univariate analysis.…”

“…However, chronic hepatitis C is an independent risk factor for severe antiretroviral hepatotoxicity, with a three-fold higher risk of grade 3 or 4 transaminitis [7][8][9]. Despite the higher risk of HAART hepatotoxicity in this population, most studies have not shown a negative impact of HCV infection on HIV virologic control [10,11]. However, most of these studies compared HIV-monoinfected patients with HIV/ HCV-coinfected patients and did not examine the influence of HCV-related variables such as liver fibrosis, HCV genotype, viral load, transaminase levels and HCV RNA positive on HIV sustained viral suppression (SVS) [10].…”

HCV RNA viral load is independent from CD4 cell count and plasma HIV RNA viral load in immunocompetent HIV-HCV co-infected patients: a 3-years follow-up study

“…There is mounting evidence on the prognostic role of HIV residual viremia (2.5-50 copies/ml) [19], and we cannot exclude the possibility that residual viremia may influence HCV RNA viral load, as could greater HIV burden. No correlation was observed between CD4+ cell count and HCV RNA values as previously described [12]; CD4+ cell count increased from T1 to T2 (mean increase of 78 cells/mm 3 , p  = 0.003). The baseline immunocompetence in our enrolled patients was greater than that reported for subjects in the study by Grint et al 576 cells/mm3 versus 340 cells/mm 3 in the subjects on ART [13].…”

“…In a cross-sectional study by Collazos et al [12], HCV RNA load was lower in subjects with undetectable HIV viremia (6.17 log 10 IU/mL versus 6.08 log 10 IU/mL, p = 0.03), whereas Grint et al [13] demonstrated that only ongoing HAART is a predictive factor of HCV viral load stability over time, with an increase of 2.6% per year compared to 27.6% in untreated subjects ( p  = 0.009). Plasma HIV viremia is a dynamic variable; patients taking antiretroviral therapy (ART) may develop virological breakthrough or experience side effects leading to treatment interruption, and untreated subjects may start antiretroviral drugs.…”

Hepatitis C virus/HIV coinfection and responses to initial antiretroviral treatment

“…While some studies have shown that HCV co-infection is associated with either smaller CD4 increases after initiation of ART [11-16] or a delayed CD4 response [17], other studies report early detected differences in CD4 response wane over time [4, 18]. Many studies have not found such an association [3, 19-25]. Most of the aforementioned studies did not report on or find any association between HCV/HIV co-infection and subjects' HIV-1 virologic responses [12, 13, 26].…”