Role of GBV-C and human herpes virus coinfections in AIDS development in HIV-1 seroconverters

Background: GB virus type C (GBV-C) co-infection prolongs survival among Human Immunodeficiency Virus (HIV) infected individuals. Chronic immune activation is associated with HIV-1 disease progression. \ud Objective: To investigate the effect of GBV-C coinfection and herpes virus reactivation on AIDS development in HIV-1 seroconverters.\ud Methods: A total of 272 men HIV-1 seroconverters were included for the analysis. Cox proportional hazards (PH) regression models were employed to evaluate the effects of GBV-C and herpes viruses (CMV, EBV, HHV6, HHV8) on time from HIV-1 seroconversion to AIDS development. In addition, Gray’s piecewise constant time-varying coefficient (PC-TVC) model that accounts for varying covariate effects over time was employed to estimate the effects for the variables that did not follow PH assumption.\ud Results: In Cox PH model analysis, GBV-C coinfection delayed AIDS development statistically significant in HIV-1 seroconverters. The log10 GBV-C RNA increase was associated with a 15% decrease in AIDS development, while the high HHV8 and CMV reactivation increased AIDS development respectively. The effects of HHV6 and EBV on AIDS development were not statistically significant. Using Gray PC-TVC model, GBV-C coinfection was associated with delaying AIDS development, especially starting from year 3 of HIV-1 infection, then the hazard ratios decreased over time until 10 years, and kept in low level after 10 years of infection. HHV8 reactivation increased the chance of AIDS development, especially after 3 years of HIV-1 infection. The effect of CMV reactivation was constant with a hazard ratio of 1.38. In addition, two variables, age and baseline CD4+ T cell counts, which were not statistically significant in Cox PH regression model analysis, were statistically significant in Gray PC-TVC model. Similar to Cox PH analysis, the effects of HHV6 and EBV were not statistically significant either on AIDS development.\ud Conclusion: GBV-C co-infection delayed HIV-1 disease progression. HHV8 and CMV accelerated AIDS development. The effects of HHV6 and EBV were not statistically significant on AIDS development.\ud Public health importance: This study has important implications for investigating viral coinfections on AIDS development and providing alternative ideas to delay HIV disease progression.\u