HIV and antiretroviral treatment as drivers of rifampicin-resistant tuberculosis in South Africa: insights from mathematical modelling

BackgroundHigh levels of multidrug and rifampicin resistant tuberculosis (MDR/RR-TB) are a global concern, although they have declined over the last decade. TB patients are at increased risk of acquired rifampicin resistance if they have HIV coinfection, especially at low CD4 counts, but this dynamic has not previously been modelled. MethodsWe extended a previously-developed model that simulates HIV and TB in South African adults, to include the acquisition and transmission of rifampicin resistance. In line with systematic reviews, the risk of acquiring RR with TB treatment is modelled as being negatively associated with patients CD4 counts. We allow for temporal changes in drug susceptibility testing, both before treatment initiation and at treatment failure, as well as other changes in TB prevention and treatment. The model is calibrated to data from national TB drug-resistance surveys, and recorded numbers of MDR/RR-TB laboratory diagnoses and patients initiating second-line TB treatment, using a Bayesian approach. ResultsThe model estimates that the proportion of South African TB patients with rifampicin resistance at diagnosis increased from 2.0% (95% CI: 1.7-2.3%) in 1986 to 5.9% (5.2-6.9%) in 2013, in line with survey data. In the absence of HIV, the prevalence of MDR/RR-TB would have increased to 4.1% (2.7-5.1%) in 2013, suggesting a third of rifampicin resistance in 2013 was attributable to HIV. In the absence of antiretroviral treatment (ART), the prevalence of rifampicin resistance would have been higher (6.5% [5.6-7.6%] in 2013, rising to 6.9% [5.7-8.2%] in 2019). ART reduced the prevalence of rifampicin resistance in 2019 by 17%. ConclusionsIn countries with high HIV prevalence, HIV may be a major driver of rifampicin resistance in people with TB. ART programmes have the potential to reduce the emergence of resistance substantially.