Increasing the use of second‐line therapy is a cost‐effective approach to prevent the spread of drug‐resistant HIV: a mathematical modelling study

IntroductionEarlier antiretroviral therapy (ART) initiation reduces HIV‐1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost‐effectiveness of strategies to reduce TDR.MethodsWe develop a deterministic mathematical model representing Kampala, Uganda, to predict the prevalence of TDR over a 10‐year period. We then compare the impact on TDR and cost‐effectiveness of: (1) introduction of pre‐therapy genotyping; (2) doubling use of second‐line treatment to 80% (50–90%) of patients with confirmed virological failure on first‐line ART; and (3) increasing viral load monitoring from yearly to twice yearly. An intervention can be considered cost‐effective if it costs less than three times the gross domestic product per capita per quality adjusted life year (QALY) gained, or less than $3420 in Uganda.ResultsThe prevalence of TDR is predicted to rise from 6.7% (interquartile range [IQR] 6.2–7.2%) in 2014, to 6.8% (IQR 6.1–7.6%), 10.0% (IQR 8.9–11.5%) and 11.1% (IQR 9.7–13.0%) in 2024 if treatment is initiated at a CD4 <350, <500, or immediately, respectively. The absolute number of TDR cases is predicted to decrease 4.4–8.1% when treating earlier compared to treating at CD4 <350 due to the preventative effects of earlier treatment. Most cases of TDR can be averted by increasing second‐line treatment (additional 7.1–10.2% reduction), followed by increased viral load monitoring (<2.7%) and pre‐therapy genotyping (<1.0%). Only increasing second‐line treatment is cost‐effective, ranging from $1612 to $2234 (IQR $450‐dominated) per QALY gained.ConclusionsWhile earlier treatment initiation will result in a predicted increase in the proportion of patients infected with drug‐resistant HIV, the absolute numbers of patients infected with drug‐resistant HIV is predicted to decrease. Increasing use of second‐line treatment to all patients with confirmed failure on first‐line therapy is a cost‐effective approach to reduce TDR. Improving access to second‐line ART is therefore a major priority.