Virological Failure After Switch to Long-Acting Cabotegravir and Rilpivirine Injectable Therapy: An In-depth Analysis.

BACKGROUND: Long-acting (LA) injectable therapy with cabotegravir (CAB) and rilpivirine (RPV) is currently used as maintenance treatment for human immunodeficiency virus type 1, and has a low risk for virological failure (VF). Although the risk is low, the circumstances and impact of VF in the real-world setting merit further evaluation. METHODS: We performed an in-depth clinical, virological, and pharmacokinetic analysis on the reasons behind and the impact of VF during LA CAB/RPV therapy in 5 cases from the Netherlands. Genotypic resistance testing was performed after the occurrence of VF, and drug plasma (trough) concentrations were measured after VF was established and on any other samples to assess on-treatment drug levels. CAB and RPV drug levels that were below the first quartile of the population cutoff (≤Q1) were considered to be low. RESULTS: Five cases who were eligible for LA CAB/RPV experienced VF despite a low predicted risk at baseline. Genotypic resistance testing revealed extensive selection of nonnucleoside reverse transcriptase inhibitor-associated mutations in all cases, and integrase strand transfer inhibitor mutations in 4 cases. All cases displayed low drug levels of either CAB, RPV, or both during the treatment course, likely contributing to the occurrence of VF. In 3 cases, we were able to identify the potential mechanisms behind these low drug levels. CONCLUSIONS: This is the first in-depth multiple case analysis of VF on LA CAB/RPV therapy in a real-world setting. Our observations stress the need to be aware for (evolving) risk factors and the yield of a comprehensive clinical, virological, and pharmacokinetic approach in case of failure.

Zidovudine continuous infusion in an HIV-infected pregnant woman with a phobia of swallowing pills.

The authors report the difficulties of preventing mother-to-child transmission in a pregnant HIV-infected woman with a phobia of swallowing pills. After multiple attempts and just as many failures, the authors ended up with cART consisting of small tablets of nevirapine, lamivudine and a continuous intravenous infusion of zidovudine given via an elastomeric pump at home. This case demonstrates the difficulties that HIV physicians can encounter in pregnant women who have difficulties in swallowing tablets. In exceptional circumstances, continuous infusion of zidovudine may be an option, even in an outpatient setting.