Markers of long-term outcomes in HIV-infected individuals receiving antiretroviral therapy.

With the availability of combination antiretroviral therapy (cART) and the subsequent reduction in AIDS and associated mortality, focus has shifted to long-term non-AIDS related complications in HIV-infected individuals. This thesis describes various biomarker studies, with an overarching goal of informing long-term management of treated HIV-infected individuals. First, changes in selected biomarkers of inflammation, coagulation and lipids, from pre- to soon after HIV-seroconversion were evaluated using a nested case-control study design. High-density lipoprotein cholesterol declined following seroconversion, which could impact on risk of future non-AIDS events.Biomarkers of long-term clinical outcomes were then assessed using large clinical cohorts. Metrics measuring chronic immunodeficiency based on CD4+ counts were evaluated for predictive value over current CD4+ counts, for of all-cause, AIDS and non-AIDS mortality. Although CD4+ count slope independently predicted all-cause and non-AIDS deaths, current CD4+ counts were overall the best predictor for all endpoints. The clinical utility of measuring D-dimer, a marker of coagulation activation, in improving risk stratification for all-cause mortality in treated HIV-infected individuals with high baseline CD4+ counts was evaluated. Inclusion of D-dimer resulted in only modest improvement in the discernment of risk of all-cause mortality.The significance of racial variation in selected biomarkers (CD4+ counts and lipids) in Asian HIV-infected individuals was examined. First, CD4+ counts were compared between Asians and whites by disease stage of untreated HIV-infection. Next, a cohort study examined if the prognostic meaning of CD4+ counts, in terms of AIDS or all-cause mortality, differs between Asian and white treated HIV-infected individuals. Collectively, findings imply that although Asians have slightly lower CD4+ counts, especially at higher CD4+ percentages; the relationship between CD4+ counts and AIDS or all-cause mortality is not different between the two groups. These findings indicate there is no need for race-specific CD4+ count thresholds for HIV management or cART initiation. Lastly, a longitudinal evaluation of differences in routinely measured lipids according to exposure to different cART regimens in Asian and white HIV infected individuals found that the impact of various cART regimens on lipids was largely similar in the two groups