1.臺灣原發性抗藥之人類免疫缺乏病毒 2.人類免疫缺乏病毒之亞型CRF07_BC之病程

Abstract

1. Transmitted Drug Resistance of HIV-1 in Taiwan Background: Drug-resistant strains of HIV-1 emerged soon after antiretroviral therapy (ART) was introduced. Transmission of the resistance mutations has been observed in 6-16% of antiretroviral-naive patients in Europe and North America and has been shown to compromise the treatment effectiveness of first-line ART. The impact of transmitted drug resistance (TDR) of HIV-1 on treatment outcome is largely unknown in areas where routine testing for drug resistance may not be available before highly active antiretroviral therapy (HAART) is initiated. Methods: Genotypic resistance assays were performed on HIV isolates from archived blood samples obtained from 1,349 antiretroviral-naive HIV-1-infected patients in Taiwan from 2000 to 2010. Resistance mutations were interpreted with the use of the HIVdb program of the Stanford University HIV Drug Resistance Database. The genotypic sensitivity score (GSS) of the regimens prescribed was calculated. A matched case–control study was conducted to assess the impact of TDR on treatment outcomes. Results: The overall prevalence of TDR to any antiretroviral agent was 8.0%, declining from 12.3% in 2003–06 to 5.1% in 2007–10. In the matched case–control study, 31 patients with high- or intermediate-level resistance, 16 with low-level resistance and 89 controls were enrolled. Compared with regimens with GSS > 2.5, initiation of regimens with GSS ≤ 2.5 was associated with a higher treatment failure rate (39.3% versus 15.7%, P = 0.02) and shorter time to treatment failure (log-rank P <0.001). In patients receiving regimens with GSS ≤ 2.5, protease inhibitor-based regimens were less likely to result in treatment failure, compared with non-nucleoside reverse-transcriptase inhibitor-based regimens (hazard ratio 0.26, 95% confidence interval 0.06–1.12, P = 0.07). Conclusions: In Taiwan, the prevalence of TDR of HIV-1 strains declined and stabilized between 2007 and 2010. Receipt of antiretroviral regimens with GSS ≤ 2.5 was associated with poorer treatment responses than regimens with GSS > 2.5. 2. Immunologic Progression of Patients Infected with HIV-1 CRF07_BC in Taiwan Background: HIV-1 circulating recombinant form (CRF) 07_BC causes serious HIV-1 epidemics in East Asia. Almost all injecting drug users (IDUs) infected in the outbreak in Taiwan between 2003 and 2007 were CRF07_BC-infected. Little is known about its influence on disease progression. Methods: IDUs diagnosed as having HIV infection between 2004 and 2007 were enrolled. The comparator group included patients with primary HIV-1 infection via sexual contacts. All participants were treatment-naive and received free-of-charge HIV care. Immunologic progression was defined as the onset of CD4 cell counts <350 cells/mm3. Results: During the study period, 384 IDUs and 191 patients of the non-IDU group were included. In the non-IDU group, 185 (96.9%) were men who have sex with men (MSM) and 94.0% of them were infected with subtype B. The IDUs were demographically different from the non-IDU group. Kaplan-Meier plots showed significantly slower immunologic progression in the IDU group (P<0.001 by log rank test). In Cox proportional hazards models, IDUs infected with CRF07_BC were associated with slower immunologic progression (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.21-0.93; P=0.03), after adjustment for age, gender, baseline CD4 cell counts and plasma HIV RNA load , and symptoms of seroconversion. Conclusions: IDUs infected with HIV-1 CRF07_BC had slower immunologic progression, compared with MSM infected with subtype B.