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Risk factors and mortality associated with resistance to first line antiretroviral therapy: multicentric cross-sectional and longitudinal analyses

  • 2015/01/12
Type of publication
  • Articles
  • Pinoges L
  • Schramm B
  • Poulet E
  • Balkan S
  • Szumilin E
  • Ferreyra C
  • Pujades-Rodriguez M
  • VIH
Understanding the factors associated with HIV drug resistance development and subsequent mortality is important to improve clinical patient management.
Analysis of individual electronic health records from four HIV programmes in Malawi, Kenya, Uganda and Cambodia, linked to data from 5 cross-sectional virological studies conducted among patients receiving first-line ART for ≥6 months. Adjusted logistic and Cox regression models were used to identify risk factors for drug resistance and subsequent mortality.
2257 patients (62% women) were included. At ART initiation median CD4 cell count was 100 cells/µL [IQR 40-165]. A median of 25.1 months after therapy start, 18% of patients had ≥400 and 12.4% ≥1000 HIV-RNA copies/mL. Of 180 patients with drug resistance data, 83.9% had major resistance(s) to nucleoside (NRTI) or non-nucleoside reverse-transcriptase-inhibitors (NNRTI), and 74.4% dual-resistance. Resistance to nevirapine, lamivudine and efavirenz were common, and 6% had etravirine cross-resistance. Risk factors for resistance were young age (<35 years), low CD4 cell count (<200 cells/µL) and poor treatment adherence. During 4978 person-years of follow-up post-virological testing (median=31.8 months), 57 deaths occurred (rate=1.14/100 person-years, 95%CI 0.88-1.48). Mortality was higher in patients with resistance (HR=2.08, 95%CI 1.07-4.07 vs. <400 copies), and older age (HR=2.41, 95%CI 1.24-4.71 ≥43 vs. ≤34 years); and lower in those receiving ART for >30 months.
Our findings underline the importance of optimal treatment adherence and adequate virological response monitoring, and emphasize the need for resistance surveillance initiatives even in HIV programs achieving high virological suppression rates