Background:  A blunted CD4⁺ cell response following a successful HAART treatment has been reported in HIV⁺ patients co-infected with hepatitis C virus (HCV); however this is still controversial and might be confounded by specific HCV genotype effects.

Methods:  Patients included in the Italian MASTER Cohort with sustained plasma viral load <50 copies/mL for at least 12 months on HAART were studied. Univariate and multivariate linear regression analyses were used with CD4⁺ cell increase as dependent variable. CD4⁺ cell increase was defined by the change between values at baseline (before starting the HAART treatment that led to HIV plasma viral load of <50 copies/mL) and after 12 months of undetectability.

Results:  We analyzed 885 patients:  684 HIV⁺ and 201 HIV/HCV⁺ (66.2% HCV genotypes 1 or 4; 33.8%, 2 or 3). Mean age was 36.8 (SD 9) years and males were 71.4%. HIV/HCV⁺ patients were younger (35.4 [4.5] vs 39.6 [10], p <0.0001) and more likely to be injection drug users (IDU; 86.8% vs 13.2 %, p <0.0001). Patients were on first (44.6%), second (19.3%), or more advanced (36.1%) line of therapy. Mean time to reach undetectable HIV plasma viral load was 112.6 (112.5) days and CD4⁺ increase was 205.1 (193.6) cells/mm³ (HIV⁺ 208 [189], HIV/HCV⁺ genotypes 1 or 4: 205 [194], genotypes 2 or 3: 143 [187]; p = 0.01), with a mean monthly CD4⁺ increase of 11.7 (11.8) cells/mm³ (11.8 [11.7]; 13 [12.4]; 8.2 [10.8], respectively; p = 0.048). At multivariate analysis, HCV genotypes 2 or 3 (vs HCV^­) were associated with blunted CD4⁺ responses (regression coefficient: –70 cells/mm³, p = 0.006), independently from age (–2, p = 0.001), occurrence of HIV plasma viral load blips (–40, p = 0.03), baseline CD4⁺ cell count (–0.2, p <0.001), high or low (cut-off:  10,000 copies/mL) HIV plasma viral load at baseline (30, p = 0.003), and advanced treatment lines (44, p = 0.03). Time to HIV plasma viral load suppression, type of drugs (including zidovudine, tenofovir/didanosine or protease inhibitor- vs non-nucleoside reverse transcriptase inhibitor-containing regimens), length and type of previous treatment exposure did not show significant associations with outcome.

Conclusions:  Patients with HIV/HCV⁺ co-infection did not show a blunted CD4⁺ cell response following 12-month complete viral suppression when compared with HIV⁺ individuals. However, having genotypes 2 or 3 HCV was significantly associated to worse CD4⁺ recovery in the presence of undetectable plasma viral load, when compared with either HIV⁺ or HIV/HCV⁺ patients infected with genotypes 1 or 4.