Context & Rationale: Individuals with similar CD4 cell counts and RNA levels can vary considerably with regards to clinical progression. This variation is likely the result of a complex interplay between viral, host and environmental factors. This study aimed to characterize and identify predictors associated with disease progression to AIDS or death in Saskatoon, Saskatchewan. Methods: This is a retrospective cohort study of 343 seroprevalent HIV positive patients diagnosed from Jan 2005 to Dec 2010. Of these, 73 had an estimated seroconversion date. Data was extracted from medical charts at two clinics specialized in HIV/AIDS care. Disease progression was measured as time from HIV diagnosis (or seroconversion) to immunological AIDS and death. The Cox hazard model was used. Results: The 3-year and 5-year immunological AIDS free probability was 53% and 33%, respectively. The 3-year and 5-year survival probability was 89% and 77%, respectively. Among the seroconversion cohort, the 3-year immunological AIDS free probability was 76%. Due to multicollinearity, separate models were built for IDU, hepatitis C and ethnicity. A history of IDU (HR, 3.0; 95%CI, 1.2-7.1), hepatitis C coinfection (HR, 2.9; 95%CI, 1.2-6.9), baseline CD4 counts (HR, 0.95; 95%CI, 0.92-0.98, per ever 10 unit increase), ever on ART, and year of diagnosis were significant predictors of progression to immunological AIDS among the seroprevalent cohort. Age at diagnosis, sex and ethnicity were not. For survival, only treatment use was a significant predictor (HR, 0.34; 95%CI, 0.1-0.8). Hepatitis C coinfection was marginally significant (p=0.067), while a history of IDU, ethnicity, gender, age at diagnosis, and year of diagnosis were not. Among the seroconversion cohort, no predictors of progression to immunological AIDS were identified. Ethnicity, hepatitis C coinfection and history of IDU could not be assessed. Conclusion: Our study found that IDU, HCV coinfections, baseline CD4 counts, and ART use were significant predictors of disease progression. This highlights the need for increased testing and early detection and for targeted interventions for these particularly vulnerable populations to slow disease progression.

Context & Rationale: Individuals with similar CD4 cell counts and RNA levels can vary considerably with regards to clinical progression. This variation is likely the result of a complex interplay between viral, host and environmental factors. This study aimed to characterize and identify predictors associated with disease progression to AIDS or death in Saskatoon, Saskatchewan. Methods: This is a retrospective cohort study of 343 seroprevalent HIV positive patients diagnosed from Jan 2005 to Dec 2010. Of these, 73 had an estimated seroconversion date. Data was extracted from medical charts at two clinics specialized in HIV/AIDS care. Disease progression was measured as time from HIV diagnosis (or seroconversion) to immunological AIDS and death. The Cox hazard model was used. Results: The 3-year and 5-year immunological AIDS free probability was 53% and 33%, respectively. The 3-year and 5-year survival probability was 89% and 77%, respectively. Among the seroconversion cohort, the 3-year immunological AIDS free probability was 76%. Due to multicollinearity, separate models were built for IDU, hepatitis C and ethnicity. A history of IDU (HR, 3.0; 95%CI, 1.2-7.1), hepatitis C coinfection (HR, 2.9; 95%CI, 1.2-6.9), baseline CD4 counts (HR, 0.95; 95%CI, 0.92-0.98, per ever 10 unit increase), ever on ART, and year of diagnosis were significant predictors of progression to immunological AIDS among the seroprevalent cohort. Age at diagnosis, sex and ethnicity were not. For survival, only treatment use was a significant predictor (HR, 0.34; 95%CI, 0.1-0.8). Hepatitis C coinfection was marginally significant (p=0.067), while a history of IDU, ethnicity, gender, age at diagnosis, and year of diagnosis were not. Among the seroconversion cohort, no predictors of progression to immunological AIDS were identified. Ethnicity, hepatitis C coinfection and history of IDU could not be assessed. Conclusion: Our study found that IDU, HCV coinfections, baseline CD4 counts, and ART use were significant predictors of disease progression. This highlights the need for increased testing and early detection and for targeted interventions for these particularly vulnerable populations to slow disease progression.

Human immunodeficiency virus (HIV) is globally spread virus without available cure. Since its life-long presence, virus is carefully monitored as well as patient's immunological status. Replicative fitness of the virus is one of important aspects which can be taken into account, when monitoring HIV. Here, we are measuring HIV replicative fitness of gag recombinant viruses and comparing the results with replicative fitness of primary isolates. Further, we are comparing our findings of replicative fitness change over time with disease progression in the patient. We found that gag can be major contributor to overall fitness, although not in all cases. Additionally, we observed a correlation of replicative fitness development and slope of patient's CD4+ T cells. Moreover, this relation was even more noticeable in patients with slow disease progression or in carriers of protective alleles. In summary, our results extend the understanding of replicative fitness and its role in disease progression; and pave the way to use the recombinant HIV for replicative fitness measurement in clinical practice. Keywords: HIV, replicative fitness, recombinant virus, HIV disease progression, gag

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.