Antiretroviral Therapy Strategies in HIV-1 Infection

Since the advent of combination antiretroviral therapy, HIV-1 infection has transitioned from a fatal disease to a manageable chronic condition. Current strategies centre on suppressing viral replication to undetectable levels, preserving immune function and minimising drug toxicity. Regimens commonly combine agents from several classes—nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), integrase strand transfer inhibitors (INSTIs), non-nucleoside reverse transcriptase inhibitors and protease inhibitors—each targeting distinct stages of the viral life cycle. First-line therapy increasingly favours single-tablet, INSTI-based regimens that offer high potency, favourable tolerability and a strong genetic barrier to resistance. Second-line and salvage therapies employ boosted protease inhibitors or newer INSTIs in combination with optimised NRTI backbones to overcome treatment failure. Innovative dual-therapy approaches are under evaluation to reduce long-term toxicity and cost while maintaining virologic suppression. The global rollout of integrase inhibitors such as dolutegravir has yielded substantial benefits but also highlighted the need for vigilant resistance monitoring, especially in settings with limited access to viral load and genotypic resistance testing. Current research focuses on refining regimen composition, extending treatment options in co-infections and resource-limited settings, and defining strategies to prevent and manage drug resistance.

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Antiretroviral Therapy Strategies in HIV-1 Infection publication trend

The graph below shows the total number of articles in antiretroviral therapy strategies in hiv-1 infection across all publications each year (not limited to Nature Index journals).

Technical terms

Antiretroviral therapy (ART): Combined use of drugs that inhibit HIV replication to achieve and maintain virologic suppression.

Integrase strand transfer inhibitor (INSTI): Class of antiretroviral agents that block the HIV integrase enzyme from integrating viral DNA into the host genome.

Viral load: Measurement of HIV RNA copies per millilitre of blood, used to assess treatment efficacy and guide therapy adjustments.

Genotypic resistance testing (GRT): Laboratory analysis that identifies mutations in the HIV genome conferring reduced drug susceptibility.

Dual therapy: Treatment regimen comprising two antiretroviral drugs, aimed at reducing toxicity and simplifying patient management while maintaining viral suppression.

References

1. Emergence of Acquired Dolutegravir Resistance in Treatment-experienced People With HIV in Lesotho. Clinical Infectious Diseases (2024).
2. Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial. The Lancet HIV (2022).
3. HIV Treatment with the Two-Drug Regimen Dolutegravir Plus Lamivudine in Real-world Clinical Practice: A Systematic Literature Review. Infectious Diseases and Therapy (2021).