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Abstract and Introduction
Abstract
Background Understanding the factors associated with HIV drug resistance development and subsequent mortality is important to improve clinical patient management.
Methods Analysis of individual electronic health records from 4 HIV programs in Malawi, Kenya, Uganda, and Cambodia, linked to data from 5 cross-sectional virological studies conducted among patients receiving first-line antiretroviral therapy (ART) for ≥6 months. Adjusted logistic and Cox-regression models were used to identify risk factors for drug resistance and subsequent mortality.
Results A total of 2257 patients (62% women) were included. At ART initiation, median CD4 cell count was 100 cells per microliter (interquartile range, 40–165). A median of 25.1 months after therapy start, 18% of patients had ≥400 and 12.4% ≥1000 HIV RNA copies per milliliter. Of 180 patients with drug resistance data, 83.9% had major resistance(s) to nucleoside or nonnucleoside reverse transcriptase inhibitors, and 74.4% dual resistance. Resistance to nevirapine, lamivudine, and efavirenz was 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 after virological testing (median = 31.8 months), 57 deaths occurred [rate = 1.14/100 person-years; 95% confidence interval (CI): 0.88 to 1.48]. Mortality was higher in patients with resistance (hazard ratio = 2.08; 95% CI: 1.07 to 4.07 vs. <400 copies/mL), and older age (hazard ratio = 2.41; 95% CI: 1.24 to 4.71 for ≥43 vs. ≤34 years), and lower in those receiving ART for >30 months.
Conclusions 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.
Introduction
Access to HIV antiretroviral therapy (ART) in sub-Saharan Africa and South-East Asia has increased considerably in the past decade. By the end of 2012, the estimated coverage in these geographical areas was 63% and 55%, respectively. The widespread use of ART has greatly improved the life expectancy and quality of life of people infected with HIV in low- and middle-income countries. The need for lifelong therapy has important implications for patients, clinicians, and program managers. Development of HIV drug resistance is frequently associated with suboptimal treatment adherence, leads to treatment failure, and compromises future treatment options, for individuals who acquired resistance as well as for those to whom resistant virus is transmitted. Identifying the main factors associated with the development of drug resistance and associated mortality is therefore critical to design, improve, and evaluate therapeutic and program management strategies that facilitate the use and effectiveness of existing and new second- and third-line regimens. This is especially important in settings where a public health approach is adopted for the clinical management of HIV-infected patients because access to new treatment options is limited. Because most resource-constrained countries have low access to regular viral load monitoring and/or drug resistance genotyping, data on virological response to ART primarily come from research settings, or more recently, from drug resistance surveys supported by the WHO Global HIV Drug Resistance Network initiative (HIVResNet).
To inform patient management strategies that prevent drug resistance development, we analyzed cross-sectional data from 3 sub-Saharan African countries with high HIV prevalence and from Cambodia to identify risk factors for drug resistance to first-line ART among adult and pediatric patients. Linking these data to patient electronic health records (EHRs), we also assessed mortality and related risk factors during the 4 years after virological testing.
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