HIV and ART shaped rifampicin-resistant TB trends in South Africa

Multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) remains a global worry even as overall levels have fallen in recent years. People with tuberculosis who also have HIV are known to be more likely to develop resistance to rifampicin during treatment, particularly when their CD4 counts are low. Until now, that link had not been built into a population-level mathematical model that also follows the spread of resistance. In new work led by Leigh F. Johnson, researchers extended an existing model of HIV and TB in South African adults to explicitly include how rifampicin resistance is both acquired during treatment and passed from person to person. The model was designed to reflect real-world changes over time in how TB is prevented and treated, and to capture the way a person’s CD4 count affects their risk of acquiring resistance. By bringing together HIV, CD4 dynamics, TB treatment, and resistance in one framework, the study aimed to quantify how much HIV and antiretroviral treatment (ART) have influenced the rise of rifampicin resistance in South Africa.

To connect the model to observed trends, the team allowed for temporal changes in drug susceptibility testing both before treatment initiation and at treatment failure, and they included other changes in TB prevention and treatment over time. The model was calibrated using 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. The model estimates that the proportion of South African TB patients with rifampicin resistance at diagnosis rose from 2.0% (95% CI: 1.7-2.3%) in 1986 to 5.9% (5.2-6.9%) in 2013, consistent with survey data. When the model removed HIV from the epidemic, the predicted prevalence of MDR/RR-TB in 2013 would have been 4.1% (2.7-5.1%), implying roughly one-third of rifampicin resistance in 2013 was attributable to HIV. The model also calculated that without antiretroviral treatment, the prevalence would have been higher — 6.5% (5.6-7.6%) in 2013 rising to 6.9% (5.7-8.2%) in 2019 — and that ART reduced rifampicin resistance in 2019 by 17%.

These findings point to two related conclusions. First, in countries with high HIV prevalence, HIV itself can be a major driver of rifampicin resistance among people with TB, because HIV-related immunosuppression (lower CD4 counts) raises the chance of acquiring resistance during TB treatment. Second, antiretroviral treatment programmes have the potential to slow the emergence of resistance substantially; in this modelled example ART lowered the prevalence of rifampicin resistance by a measurable amount by 2019. By combining drug susceptibility testing trends, second-line treatment starts, and survey data in a calibrated mathematical framework, the study provides a way to estimate how much of drug resistance is driven by coinfection dynamics versus transmission. The results support the idea that integrating strong HIV care, timely ART, and robust TB resistance surveillance can be important parts of strategies to contain MDR/RR-TB in high-burden settings like South Africa.