Durability of Response to Treatment among Antiretroviral‐Experienced Subjects: 48‐Week Results from AIDS Clinical Trials Group Protocol 359

Abstract

The 24-week extension of AIDS Clinical Trials Group Protocol 359, a study of human immunodeficiency virus (HIV)-infected, indinavir-experienced patients, was designed to study the durability of "salvage" treatment regimens. Patients received saquinavir in combination with either ritonavir or nelfinavir and, in addition, delavirdine, adefovir, or both. Patients who demonstrated a virologic response at weeks 12-16 were eligible to continue therapy in the extension through week 48. Of the 105 eligible subjects who were enrolled in the extension, 86 (82%) completed 48 weeks, and 49 (57%) of those 86 had HIV RNA levels <or=500 copies/mL at week 48. For these 86 subjects who completed 48 weeks, the median change in CD4 cell count from baseline was +72 cells/mm(3). Greater body weight, higher CD4 cell count, and greater degree of phenotypic susceptibility to indinavir and saquinavir at baseline were significantly associated with durable virologic suppression. These results show that some patients who experience treatment failure can demonstrate durable virologic and immunologic responses with salvage antiretroviral regimens.

Four Measures of Antiretroviral Medication Adherence and Virologic Response in AIDS Clinical Trials Group Study 359

“…10,11 The regimens were saquinavir soft gelatin capsules (hereafter referred to as saquinavir) plus ritonavir together with delavirdine (group A), adefovir dipivoxil (group B), or both (group C), and saquinavir plus nelfinavir together with delavirdine (group D), adefovir dipivoxil (group E), or both (group F). Study subjects were HIV-infected adults who had taken indinavir for at least 6 months and had screening plasma HIV RNA levels of 2000-200,000 copies/mL (Amplicor HIV Monitor Test, version 1.0, Roche Diagnostic Systems, Branchburg, NJ; lower limit of quantification, 500 copies/mL).…”

“…The complete details and the week 16 and week 48 results have been published. 10,11 In ACTG 359, only 77 of 254 subjects (30%) achieved the primary virologic endpoint of #500 copies/mL of HIV RNA at week 16. 10 Four putative methods of measuring adherence were evaluated in ACTG 359: counts of returned medications, patient selfreport, electronic monitoring of medication bottle opening, and quantitation of protease inhibitor concentrations in plasma.…”

Sex‐Based Differences in Saquinavir Pharmacology and Virologic Response in AIDS Clinical Trials Group Study 359

“…The complete details of the design of ACTG 359 and the week-16 and week-48 results have been published elsewhere [5,6]. At week 16, only 77 (30%) of 254 patients in ACTG 359 achieved the primary virologic end point of an HIV RNA level р500 copies/mL [5].…”

Weighted Phenotypic Susceptibility Scores Are Predictive of the HIV‐1 RNA Response in Protease Inhibitor–Experienced HIV‐1–Infected Subjects

“…In our study, an initial model relating therapy to outcome, with all drugs treated as being equally potent and scored as active [31]. The further improvement in the strength of the model when examining a treatment outcome of nadir VL (table 4) suggests that the drugs act equivalently at low and high VLs (at the time of entry) but act to inhibit a fraction of the total viral replication.…”

“…AIDS Clinical Trials Group (ACTG) Study 359 was a randomized clinical trial of 6 combination antiretroviral regimens for indinavir-experienced subjects with virologic failure [30,31]. Overall in that study, only 30% of the subjects had VL decreases to р500 copies/mL at week 16.…”