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INTRODUCTION: Emerging non-AIDS related causes of death have been observed in HIV-positive subjects in industrialized countries. We aimed to analyze overall and cause-specific excess of mortality of HIV-positive patients compared to the general population and to assess the effect of prognostic factors. MATERIAL AND METHODS: We used generalized linear models with Poisson error structure to estimate overall and cause-specific excess of mortality in HIV-positive patients from 2004 to 2012 in the cohort of the Spanish Network of HIV Research (CoRIS), compared to Spanish general population and to assess the impact of multiple risk factors. We investigated differences between short-term and long-term risk factors effects on excess of mortality. Multiple Imputation by Chained Equations was used to deal with missing data. RESULTS: In 9162 patients there were 363 deaths, 16.0% were non-AIDS malignancies, 10.5% liver and 0.3% cardiovascular related. Excess mortality was 1.20 deaths per 100 person years (py) for all-cause mortality, 0.16 for liver, 0.10 for non-AIDS malignancies and 0.03 for cardiovascular. Short-term (first-year follow-up) excess Hazard Ratio (eHR) for global mortality for baseline AIDS was 4.27 (95% CI 3.06-6.01) and 1.47 (95% CI 0.95-2.27) for HCV coinfection; long-term (subsequent follow-up) eHR for baseline AIDS was 0.88 (95% CI 0.58-1.35) and 4.48 (95% CI 2.71-7.42) for HCV coinfection. Lower CD4 count and higher viral load at entry, lower education, being male and over 50 years were predictors for overall excess mortality. Excess of liver mortality was higher in patients with CD4 counts at entry below 200 cells compared to those above 350 (eHR: 6.49, 95% CI 1.21-34.84) and in HCV-coinfected patients (eHR: 3.85, 95% CI 0.85- 17.37), although it was borderline significant. Patients over 50 years old (eHR: 5.55, 95%CI 2.4-12.85) and HCV coinfected (eHR: 5.81, 95% CI 2.6-13) showed a higher risk of non-AIDS malignancies mortality excess. Excess of cardiovascular mortality was related with HCV coinfection (eHR: 6.68, 95% CI 1.25-35.73). CONCLUSIONS: Our results show overall, liver, non-AIDS malignancies and cardiovascular excess of mortality associated with being HIV-positive, despite improvements in HIV disease management and antiretroviral therapies. Differential short-term and long-term effect of AIDS before entry and HCV coinfection was found for overall mortality.
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BACKGROUND: The wide use of lamivudine (3TC) as oral therapy for chronic HBV infection has favoured the selection and circulation of 3TC-resistant HBV strains worldwide. Although transmission of 3TC-resistant HBV variants has been reported only sporadically, few studies have been conducted in the HIV population where exposure to 3TC has been greater forming part of antiretroviral therapy (ART) regimens. METHODS: All individuals positive for serum hepatitis B surface antigen (HBsAg), newly diagnosed with HIV-1 infection, naive to ART and enrolled in the Spanish HIV cohort (CoRIS) since 2004 were identified. The HBV polymerase gene was sequenced and drug resistance mutations were characterized retrospectively in stored frozen plasma specimens. RESULTS: From 4,419 ART-naive HIV-1-infected individuals, 223 (5.1%) were positive for serum HBsAg. Baseline stored sera were available for 84 patients, of whom 73 could be characterized virologically. This population was mainly represented by men who had sex with men (52.1%), native Spaniards (65.7%) and Latin Americans (16.4%). The mean age was 36 years, mean CD4(+) T-cell count 375 cells/mm(3) and mean plasma HIV RNA 4.5 log(10) copies/ml. The HBV genotype distribution was 64% A, 20% F, 12% D and 4% others. Drug-resistant mutations in the HBV polymerase were found in four (5.5%) patients: two harboured rtL180M, one rtL80V and one rtV173L. CONCLUSIONS: The rate of primary drug resistance in HBV among newly diagnosed HIV-HBV-coinfected patients in Spain is currently low (5.5%) and restricted to 3TC. Thus, HBV drug resistance testing before prescription of oral antiviral therapy is not warranted, although periodic surveillance might be recommended.