Protease inhibitor monotherapy

To reduce drug side-effects and improve treatment convenience and adherence, researchers have studied the use of single ritonavir-boosted protease inhibitors as monotherapy. Even though this approach uses two drugs, it is still considered monotherapy because the boosting dose of ritonavir is too low to control HIV.

While NRTI monotherapy in the early years of the HIV epidemic led to the rapid emergence of drug resistance and subsequent treatment failure, some studies of ‘second-generation’ protease inhibitor monotherapy have shown promising results in a carefully selected subset of patients.

Protease inhibitor monotherapy has been explored as first-line therapy, part of an induction and maintenance strategy, and as a way to simplify regimens in individuals who are stable on combination antiretroviral therapy. Below is a listing of some of the trials using boosted lopinavir or atazanavir as an initial monotherapy first-line regimen.

The IMANI-1 pilot study was a proof of concept study using lopinavir/ritonavir (Kaletra) as monotherapy. The 30 treatment-naive patients had an average viral load greater than 200,000 copies/ml. At 48 weeks, 67% achieved a viral load below 50 copies/ml with an average CD4 gain of 317 cells/mm³.¹

In the IMANI-2 open-label prospective pilot study, 74% of the 39 antiretroviral-naive participants on single agent lopinavir/ritonavir therapy demonstrated durable virologic control through 96 weeks of therapy. In the 'as-treated' analysis, 88% of participants achieved viral load less than 75 copies/ml. The median CD4 gain was 310 cells/mm³. Virologic failure was attributed to concurrent illness or adherence failure.²

In the open-label MONARK (Monotherapy antiretroviral Kaletra) trial, 136 previously untreated participants with a baseline viral load above 100,000 copies/ml were randomly assigned to start treatment with lopinavir/ritonavir monotherapy or lopinavir/ritonavir plus AZT/3TC. Achieving viral load below 50 copies/ml by week 48 was a primary endpoint met by (using on-treatment analysis) 80% in the monotherapy arm and by 95% in the combination therapy arm. The monotherapy approach was not recommended by the study investigators.³ 

Clinical trials looking at protease inhibitor monotherapy use in treatment-experienced individuals for regimen simplification or maintenance are discussed in the section Investigational maintenance regimens in the Changing HIV treatment section.

Current UK and US treatment guidelines do not recommend protease inhibitor monotherapy for patients initiating antiretroviral treatment or seeking a simpler regimen.