Alternative Administration of Antiretroviral Therapy in People with HIV Unable to Swallow: A Scoping Review

To review published evidence on alternative administration methods for antiretroviral therapy in patients unable to swallow tablets.

We conducted a scoping review using PubMed, Web of Science, and Google Scholar databases from 2011 to 2025. We included studies reporting pharmacokinetic data, clinical outcomes, or safety data on crushed, dispersed, or enterally administered antiretroviral formulations. Four independent reviewers screened 1,474 articles after duplicate removal, with 12 studies meeting selection criteria.

We identified 12 studies (8 case reports, 2 case series, 2 cohort studies) describing alternative administration of antiretrovirals. Key findings included: (1) Bictegravir/emtricitabine/tenofovir alafenamide was associated with viral suppression when dissolved and administered enterally; (2) Dolutegravir/abacavir/lamivudine crushed via nasogastric tube was associated with viral suppression within 10 months; (3) Dolutegravir requires separation from enteral feeds containing polyvalent cations to avoid chelation and reduced absorption. (4) Most nucleoside reverse transcriptase inhibitors (NRTIs) could be crushed or dissolved, while non-nucleoside reverse transcriptase inhibitors (NNRTIs) showed variable stability. (5) Therapeutic drug monitoring was recommended for integrase inhibitors administered enterally.

This review provides evidence suggesting the use of modified ART formulations when standard oral administration is not possible. In situations where swallowing difficulties prevent the use of whole tablets, alternative methods such as crushing, or dissolving may offer a practical approach to maintain treatment continuity. Alternative administration ART, namely INSTI-based regimens and NRTIs, may help maintain viral suppression in these settings, provided that drug-specific pharmacokinetic considerations and enteral feeding interactions are addressed. Further prospective studies with therapeutic drug monitoring are needed to establish standardized protocols.