Rates and factors associated with major modifications to first-line combination antiretroviral therapy: results from the Asia-Pacific region

Abstract

Background: In the Asia-Pacific region many countries have adopted the WHO's public health approach to HIV care and treatment. We performed exploratory analyses of the factors associated with first major modification to first-line combination antiretroviral therapy (ART) in resource-rich and resource-limited countries in the region.

Methods: We selected treatment naive HIV-positive adults from the Australian HIV Observational Database (AHOD) and the TREAT Asia HIV Observational Database (TAHOD). We dichotomised each country's per capita income into high/upper-middle (T-H) and lower-middle/low (T-L). Survival methods stratified by income were used to explore time to first major modification of first-line ART and associated factors. We defined a treatment modification as either initiation of a new class of antiretroviral (ARV) or a substitution of two or more ARV agents from within the same ARV class.

Results: A total of 4250 patients had 961 major modifications to first-line ART in the first five years of therapy. The cumulative incidence (95% CI) of treatment modification was 0.48 (0.44-0.52), 0.33 (0.30-0.36) and 0.21 (0.18-0.23) for AHOD, T-H and T-L respectively. We found no strong associations between typical patient characteristic factors and rates of treatment modification. In AHOD, relative to sites that monitor twice-yearly (both CD4 and HIV RNA-VL), quarterly monitoring corresponded with a doubling of the rate of treatment modifications. In T-H, relative to sites that monitor once-yearly (both CD4 and HIV RNA-VL), monitoring twice-yearly corresponded to a 1.8 factor increase in treatment modifications. In T-L, no sites on average monitored both CD4 & HIV RNA-VL concurrently once-yearly. We found no differences in rates of modifications for once- or twice-yearly CD4 count monitoring.

Conclusions: Low-income countries tended to have lower rates of major modifications made to first-line ART compared to higher-income countries. In higher-income countries, an increased rate of RNA-VL monitoring was associated with increased modifications to first-line ART.

Figure 1. Time to first major modification of ART (any reason) by country income grouping.

Cumulative Incidence are adjusted for competing risk of death (solid line) with mean 95% confidence bands. Sensitivity analysis (dashed line) adjusts for competing risk of death or lost to follow-up.

Figure 2. Time to first major modification of ART by country income grouping stratified by reported reason for modification.

Panel (a) - reported treatment failure, Panel - (b) adverse event/toxicity, Panel (c) - patient/physician decision. Cumulative Incidence are adjusted for competing risk of death and competing reasons for modification. Shaded bands are mean 95% confidence bands.

Figure 3. Multivariable adjusted associations for site resourcing and time to major first-line ART modification.

Income group-specific models are adjusted for age, sex, exposure, HBV, HCV, pre-ART AIDS illness, pre-ART CD4, pre-ART RNA-VL and year of ART initiation.