Back Back
CROI 2024 HIV and TB Coinfection
Treating and Preventing TB Coinfection in People Living With HIV

Released: April 04, 2024

Expiration: April 03, 2025

Yan Zhao
Yan Zhao, MD, PhD
Activity Information

Activity

Progress
1
Course Completed
Key Takeaways
  • HIV and TB coinfection is a global public health issue affecting Southeast Asian countries.
  • For people living with HIV who are receiving rifampicin-based treatment for TB, twice-daily BIC/FTC/TAF is an effective ART option.
  • In treatment-naive people living with HIV who are starting routine ART, studies support simultaneous initiation of TB preventive treatment. 

HIV and tuberculosis (TB) coinfection is a global public health issue. According to the WHO 2023 global report, approximately 6.3% of the estimated global population of 10.6 million people who developed TB in 2022 were living with HIV. Although Southern Africa is the most affected region (accounting for more than one half of the world’s HIV-associated TB cases), Southeast Asia has the highest overall burden of TB, accounting for nearly one half of global TB cases. Therefore, Southeast Asia also bears a substantial burden of HIV and TB coinfection.

Because TB remains a top cause of death among people living with HIV, it is critical to employ TB prevention options and prescribe effective antiretroviral therapy (ART) and TB treatment combinations in people living with HIV with concurrent TB. I would like to highlight 3 studies presented at CROI 2024 that provide new data and insights into HIV and TB coinfection prevention and management.

Rifampicin Plus ART: Treating HIV and TB Coinfection
In people living with HIV with concurrent TB, drug‒drug interactions between ART and anti-TB agents are an important consideration. Rifampicin and rifabutin are known to induce drug-metabolizing enzymes along the CYP450 pathway, with rifampicin being the stronger inducer. These enzymes are responsible for the metabolism of most ART in clinical use, including protease inhibitors and integrase strand transfer inhibitors (INSTIs). Therefore, concurrent use of rifampicin or rifabutin with a protease inhibitor or an INSTI can lead to a decrease in ART concentration and subsequent potential loss of efficacy.

WHO guidelines note that, when used concurrently with rifampicin, the dosage of the INSTI dolutegravir (DTG) should be doubled to maintain therapeutic concentrations and virologic efficacy. However, results from the RADIANT-TB trial indicate that the 24-week virologic suppression rates of a standard vs double dose of DTG in patients living with HIV with concurrent TB are similar—potentially negating the need for doubling the DTG dose as indicated in the guidelines.

And what about the INSTI bictegravir (BIC)? From CROI 2024, a report on the phase IIb INSIGHT trial indicated that twice-daily BIC/emtricitabine (FTC)/tenofovir alafenamide (TAF) was highly effective and well-tolerated through Week 24 in adults living with HIV with concurrent TB using a rifampicin-based regimen compared with once-daily DTG/lamivudine (3TC)/tenofovir disoproxil fumarate (TDF) plus a 50-mg additional dose of DTG (standard of care). Viral suppression rates in the intention-to-treat population were 95% for both groups, and there were no treatment failures. No adverse events led to treatment discontinuation, withdrawal, or a treatment switch. Although TB treatment with rifampicin lowered BIC trough concentrations, levels remained above inhibitory quotient 1.

This study suggests that twice-daily BIC/FTC/TAF may be an ART option for people living with HIV who are receiving a rifampicin-based TB regimen. This is an important study for countries with access to BIC/FTC/TAF as first-line ART. The Chinese medical insurance system provides this regimen.

TB Prevention in People Living With HIV
In addition to improving TB treatment in people living with HIV, preventing TB in people living with HIV is also a priority. The combination of TB preventive treatment plus ART can significantly reduce the risk of TB and TB-related death in people living with HIV. Furthermore, these protective effects have been proven to last at least 5 years.

The WHO recommends TB preventive treatment for people living with HIV, and the latest preventive treatment recommendations identify several options that are shorter in duration than the standard 6 months of isoniazid, including isoniazid in combination with rifampicin or rifapentine, or rifampicin alone.

IMPAACT4TB Research Group: DOLPHIN-TOO Study
At CROI 2024, the investigators of the open-label phase I/II DOLPHIN-TOO trial reported on the efficacy of ART plus rifapentine-based TB preventive treatment in ART-naive people living with HIV in South Africa.

Although both arms received DTG-based ART, one arm received 3 months of weekly isoniazid plus rifapentine (3HP), and the other arm received 6 months of isoniazid monotherapy (6H).

Rifapentine had a 72% induction effect on DTG clearance in the 3HP arm, and DTG concentrations in both groups achieved 100% viral suppression at Week 8. Therefore, simultaneous initiation of 3HP and 6H with DTG-based ART resulted in rapid viral suppression among people living with HIV who had not previously received ART. These data are critical for informing guidelines on TB prevention in this particular patient population.

TB SCRIPT Study 
Furthermore, an updated analysis of the phase III TB SCRIPT trial presented at CROI 2024 reported on the efficacy and safety of DTG-based ART plus rifapentine-based TB preventive treatment in people living with HIV in Uganda who were initiating ART. This study compared 3HP plus DTG/3TC/TDF vs DTG/3TC/TDF alone.

The results showed no significant difference in viral suppression with 3HP plus DTG/3TC/TDF vs DTG/3TC/TDF alone at 6 months (72.7% vs 72.8%) and 12 months (76.3% vs 77.3%). In addition, 3HP plus DTG/3TC/TDF was safe, well-tolerated, and equally effective in achieving viral suppression, as was DTG/3TC/TDF alone.

Both of these studies on TB prevention support the initiation of TB preventive treatment in people living with HIV who are treatment naive and starting routine ART simultaneously. This is a key preventive measure for reducing the incidence of TB in regions with high rates of HIV and TB coinfection, such as Southeast Asia.

Your Thoughts?
How often do you prescribe TB preventive treatment for your adult and adolescent patients living with HIV? Join the conversation by posting a comment.