Combo treatment to solve TB-HIV co-infection crisis: Study

Rafiqul Islam Azad: New clinical trial findings reveal a significant breakthrough in combating the co-infection crisis of tuberculosis (TB) and human immunodeficiency virus (HIV). The trial, conducted to assess the compatibility of two potent treatments, sheds light on the effectiveness of combining dolutegravir (DTG)-based antiretroviral therapy (ART) with 3HP, a three-month regimen of isoniazid and rifapentine for TB prevention.

Presented at the 2024 Conference on Retroviruses and Opportunistic Infections (CROI) in Denver, Colorado, the results underscore the safety and efficacy of simultaneously initiating DTG-based ART and 3HP TB preventive treatment. This development holds profound implications for addressing the daunting health threat posed by TB-HIV co-infection, particularly in sub-Saharan Africa and across the globe.

Dr. Ethel Weld, MD PhD, Assistant Professor of Medicine at the Johns Hopkins University School of Medicine and the principal investigator of the study, emphasizes the importance of preventive measures in averting the need for extensive treatment. “An ounce of prevention is worth a pound of cure, and early intervention is paramount. This study examined the safety, efficacy, and drug interactions of DTG when administered concurrently with 3HP to newly diagnosed HIV patients. Despite expected interactions, DTG effectively suppressed HIV viral loads, demonstrating the safety and tolerability of the combination.”

The trial, dubbed “DOLPHIN-TOO,” focused on evaluating DTG drug concentrations in the blood of HIV patients initiating ART for the first time, concurrently with either 3HP or the standard six-month regimen of isoniazid (6H). Notably, the 3HP regimen emerged as the preferred option due to its patient preference, reduced toxicity, and higher completion rates compared to the longer 6H course.

Assessment of DTG blood levels revealed slightly lower concentrations in the 3HP group compared to the 6H group. However, participants in the 3HP cohort achieved viral suppression within eight weeks and maintained it throughout the six-month study period. Importantly, adverse effects were minimal, with none deemed severe, and the majority resolved with continued therapy.

The findings underscore the viability of short-course TB preventive treatment for newly diagnosed HIV patients at heightened risk of TB infection. This pivotal research is poised to inform global policy recommendations by organizations such as the World Health Organization (WHO) on the optimal timing of TB preventive treatment initiation in high-burden TB settings.

The study builds upon previous investigations conducted by the Unitaid-funded IMPAACT4TB consortium, which established the safety of 3HP in HIV patients already on DTG-based ART. These efforts have not only spurred increased demand for the product but also led to a reduction in its cost, facilitating widespread access to short-course TB preventive therapy and potentially saving 150,000 lives by 2035.

Professor Gavin Churchyard, Group CEO of the Aurum Institute, advocates for the integration of TB preventive treatment into HIV care protocols at the outset of ART initiation. “Early initiation of TB preventive treatment aligns with patients’ close monitoring during ART initiation, enabling prompt detection of any adverse effects. The demonstrated safety and efficacy of simultaneous DTG and 3HP initiation call for its adoption in TB-endemic regions worldwide.”

Mike Frick, Co-director of the TB program at the Treatment Action Group, underscores the urgency of incorporating 3HP into HIV treatment programs from the onset. “This research provides unequivocal support for the integration of 3HP into HIV care, both for treatment-experienced and treatment-naive individuals. National governments and donors must prioritize the procurement of 3HP to safeguard the health and well-being of individuals living with HIV.”