Boosted Protease Inhibitor Monotherapy Research Articles

Assessment of Baseline HIV Viral Load as a Risk Factor for Loss of Virologic Suppression in Protease Inhibitor-Based Monotherapy Trials

To the Editors: We read with interest the article by Arribas et al1 that compared the efficacy of Lopinavir-Ritonavir monotherapy versus Lopinavir-Ritonavir and two nucleoside analogues for maintenance antiretroviral therapy after 96 weeks of treatment. Boosted protease inhibitor (PI) monotherapy, as initial monotherapy or in HIV patients already stabilized with triple therapy, is an attractive option that promises, if proved efficacious, convenience and less side effects. There is a need, however, to carefully define patient eligibility for that option. Arribas et al1 argue in the discussion of their study that the most likely explanation for the loss of virologic suppression was suboptimal adherence. In our opinion, another type of analysis worth pursuing in trying to explain the loss of virologic suppression is one that takes into account the baseline HIV viral load. Traditionally, the stratification of HIV patients according to baseline HIV viral load in clinical trials has been made at the level of 100,000 copies/mL. It is well known from early trials of antiretroviral treatment that, even with dual nucleoside analogue therapy, up to 50% of patients could “become undetectable” (<50 copies/mL) at 24 weeks.2 We also know, from anecdotal and personal experience, that patients with a low baseline HIV viral load treated with dual nucleoside analogue therapy can keep HIV viral load below 50 copies/mL for longer periods of time. We propose that, for the trial published by Arribas et al and for other boosted PI monotherapy trials to come, patients have to be stratified and analyzed according to baseline HIV viral load in multi strata, starting probably from 10,000 copies/mL and using increments of 10,000 up to over 100,000 copies/mL. Stratifying patients that way, we will probably identify a subpopulation of HIV-positive people in whom the concept of boosted PI monotherapy could be applied with more predictable efficacy and safety. Vassilios Papastamopoulos, MD Ioannis G. Baraboutis, MD Ourania Gerogiou, MD Athanasios T. Skoutelis, MD Evaggelismos General Hospital, Athens, Greece

Response to: “Assessment of Baseline HIV Viral Load as a Risk Factor for Loss of Virologic Suppression in Protease Inhibitor-Based Monotherapy Trials”

To the Editors: We appreciate the comments from Papastamopoulos et al about the possible role of baseline viral load as a predictive factor of the success of lopinavir-ritonavir monotherapy. In this context, the word “baseline” might be confusing because, in the OK04 trial, at baseline, all patients had suppression of viral replication. “Pre-HAART” (highly active antiretroviral therapy) viral load is probably a more precise term than “baseline” in a trial of boosted protease inhibitor monotherapy for maintenance of HIV viral suppression. We have carefully looked at risk factors for loss of virologic suppression in patients receiving lopinavir/ritonavir monotherapy for maintenance of HIV suppression in the OK trials.1 We have used a Cox proportional hazard model that included the following variables: age, sex, route of HIV-1 infection, previous AIDS diagnosis, viral load before starting HAART, baseline CD4+ T-cell count, nadir CD4+ T-cell count, duration of virologic suppression while on HAART before monotherapy, duration of HAART before monotherapy, baseline hemoglobin, use of lopinavir-ritonavir as the first protease inhibitor, medication adherence, baseline total cholesterol, baseline triglycerides, and high-density lipoprotein cholesterol. With use of this model, the only independent variables associated with loss of virologic suppression were two or more visits with self-reported missed doses in the week before the study visit, a lower baseline hemoglobin, and a nadir CD4+ T-cell count less than 100 cells/μL. Pre-HAART viral load (analyzed as a continuous variable) was not independently associated with failure of lopinavir-ritonavir monotherapy (hazard ratio per 1 log10 copies/mL increase: 1.5, confidence interval 95% 0.67-3.34; P = 0.32). Similar findings have been reported by other authors.2 Jose R. Arribas, MD* Federico Pulido, MD† *Hospital La Paz, HIV Unit †Hospital Doce de Octubre, HIV Unit Madrid, Spain

The Monark trial: where now for boosted protease inhibitor monotherapy?

The Monark trial: where now for boosted protease inhibitor monotherapy?

Efficacy of boosted protease inhibitor monotherapy in patients with complex medical problems

The efficacy of boosted protease inhibitor monotherapy (BPIm) in HIV-positive patients with complex medical problems was assessed in ten patients. With BPIm, median (range) HIV viral load reduction was log10 2.15 (1.62-3.1) by 4-8 weeks; in four patients, viral load was < 400 copies/ml. During follow-up, at median (range) = 50 (8-156) weeks, no patient had an opportunistic illness; one patient developed new PI mutations after 48 weeks. These very preliminary data need further confirmation on a larger scale.

Short-course induction with boosted saquinavir monotherapy for naive patients with late-stage infection

This study assessed the efficacy of short-course induction treatment with saquinavir/ritonavir as boosted protease inhibitor monotherapy in antiretroviral-naive patients, before switching to conventional highly active antiretroviral therapy. Twenty-eight patients were enrolled, with baseline CD4 cell counts of 26 cells/microl and HIV RNA 5.5 log10 copies/ml. There was a median 2.5 log10 reduction in HIV RNA and 115 cell increase in CD4 cell counts after 4-8 weeks of saquinavir/ritonavir monotherapy. This treatment strategy should be evaluated further.