Drug Interactions in HIV and Tuberculosis Treatments

Co-infection with HIV and tuberculosis (TB) presents a formidable therapeutic challenge owing to extensive drug–drug interactions that can undermine efficacy, increase toxicity and compromise patient adherence. Key interactions occur between antiretroviral agents—particularly protease inhibitors and integrase inhibitors—and first-line anti-TB drugs such as rifampicin, rifabutin and isoniazid. Rifampicin induces cytochrome P450 enzymes and drug transporters, leading to substantial reductions in plasma concentrations of protease inhibitors (for example, lopinavir/ritonavir) and certain integrase inhibitors (notably dolutegravir), which may precipitate virological failure. Conversely, some antiretrovirals can inhibit rifamycin metabolism, raising the risk of hepatotoxicity. Strategies to manage these interactions include dose escalation, therapeutic drug monitoring, substitution of rifampicin with rifabutin or use of “super-boosted” regimens. Recent advances also explore multitarget molecules active against both HIV and Mycobacterium tuberculosis, aiming to simplify regimens, mitigate cumulative toxicity and curb the emergence of resistance. An integrated understanding of pharmacokinetics, pharmacodynamics and host factors—such as age, weight and nutritional status—is critical to optimise co-treatment outcomes and to inform global guidelines for resource-limited and high-burden settings.

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Drug Interactions in HIV and Tuberculosis Treatments publication trend

The graph below shows the total number of articles in drug interactions in hiv and tuberculosis treatments across all publications each year (not limited to Nature Index journals).

Technical terms

Drug–drug interaction (DDI): Alteration of the pharmacokinetics or pharmacodynamics of one drug by co-administration of another, affecting efficacy or safety.

Protease inhibitor (PI): A class of antiretroviral drugs that block HIV protease, essential for viral maturation; often boosted with ritonavir to enhance plasma levels.

Rifamycins: A family of anti-TB antibiotics (rifampicin, rifabutin) that induce cytochrome P450 enzymes, leading to accelerated metabolism of co-administered drugs.

Pharmacokinetics (PK): The study of drug absorption, distribution, metabolism and excretion over time, crucial for optimising dosing in co-treated patients.

Molecular hybridisation: A medicinal chemistry approach that fuses pharmacophores of two bioactive molecules into a single compound to target multiple pathogens or pathways.

References

1. Pharmacokinetics and Safety of Twice-daily Ritonavir-boosted Atazanavir With Rifampicin. Clinical Infectious Diseases (2023).
2. Population pharmacokinetics of rifabutin among HIV/TB co-infected children on lopinavir/ritonavir-based antiretroviral therapy. Antimicrobial Agents and Chemotherapy (2024).
3. A Review of the Development of Multitarget Molecules against HIV-TB Coinfection Pathogens. Molecules (2023).