The Body Covers: The XIII International AIDS Conference
Clinical Trials Posters
July 12, 2000
Responses to salvage combination therapy with efavirenz in patients with HIV who have failed antiretroviral therapy with a protease inhibitor (Poster, WePeB4155)
Efavirenz-Containing Regimens for Protease Inhibitor FailuresThis retrospective study from Canada evaluated patients whose viral loads were greater than 500 on at least one PI-based regimen, who were subsequently switched by their physician to an efavirenz (EFZ)-based combination and had at least one viral load test after the switch. Fifty-one patients met these criteria; 94% were male, 90% were white. Their average baseline viral load and CD4 cell counts were 4.46 logs and 233 cells, respectively. Of these 51, 16 had resistance testing by genotypic analysis performed before the switch. Seventeen patients (33%) achieved a viral load less than 50 copies (complete responders), and 14 (27%) had a decrease of at least one log. Significant predictors of achieving a viral load less than 50 included: the patient's baseline viral load, the number of previous PIs received, and receipt of a prior NNRTI, such as delavirdine or nevirapine. Non-responders who had been genotyped prior to the switch were much more likely to have mutations that are associated with resistance to NNRTIs, including efavirenz. Ten of 12 non-responders had one or more NNRTI mutations, compared to one mutation among the three complete responders.
Resistance to NNRTIs as detected by genotypic analysis impairs response to an EFZ-based salvage regimen. In order to get the best possible benefit from a second or third regimen, information about resistance will be helpful in choosing the right regimen.
Prospective, multicenter study of ddI plus hydroxyurea (HU) plus efavirenz (EFV) plus protease inhibitor (PI) salvage therapy. One-year of follow-up. Correlation of viral outcome and genotypic mutations (Poster, WePeB4164)
ddI, Hydroxyurea, Efavirenz, and a PI as Salvage TherapyThis combination was used in an Italian multicenter study of patients who had failed at least two prior antiretroviral combinations. The protease inhibitor was selected on the basis of the patient's prior treatment history, and included nelfinavir, ritonavir/saquinavir, and ritonavir/indinavir, although only the data for the nelfinavir group was presented at this meeting. Participants had viral loads of at least 1,000 copies at study entry, and could not have previously been treated with an NNRTI or nelfinavir. All patients had a genotypic resistance test performed at entry. The median number of NRTI mutations was low at two, while the median number of protease mutations was four. Virologic response was defined as less than 200 copies, and patients were followed for up to 12 months.
Fifty-one patients received ddI, HU, EFZ and nelfinavir. Baseline viral load was 4.68 logs and CD4 cells were 316. At 12 months, 11 out of 27 patients (41%) had viral loads less than 200, of whom seven also had viral loads less than 50 copies. In a multivariate analysis, having fewer than two mutations to NFV predicted virologic response, with 85% having a viral load less than 200, compared to 23% who were responders and had two or more mutations. Only 11% of patients had to have HU or NFV stopped due to toxicity.
This study describes yet another combination of drugs that includes EFZ that can be used to treat patients with multiple prior regimen failures as long as their virus is fully susceptible to EFZ and genotyping is used to define the optimal regimen. In this study, the limited number of NRTI mutations likely made it easier to choose such a regimen.
Virologic response to indinavir (IDV), efavirenz (EFV) and adefovir (ADV) among patients failing nelfinavir (NFV) (Poster, WePeB4169)
Indinavir, Efavirenz, and Adefovir Salvage Therapy for Nelfinavir FailuresTwenty-nine patients who had never been treated with NNRTIs and adefovir, an investigational nucleotide RTI, were genotyped before switching to efavirenz, indinavir, and adefovir. The average viral load prior to switching was about 16,000 copies. Virologic response was defined as 2 consecutive viral load results less than 400 copies. Sixteen patients (62%) responded to the new regimen. Ten patients discontinued study therapy, including three for non-response and four for toxicity. Eleven patients with the L90M mutation had a poorer response than the 17 patients with the D30N mutation. After 24 weeks, patients with L90 had a viral load decrease of less than one log (0.78 log), while the D30 patients had a decrease of 1.61 logs.
This three-drug combination provided effective salvage therapy for patients who had failed nelfinavir. Genotypic resistance to nelfinavir can take one of two pathways: L90 or D30. Since the D30 mutation is unique to nelfinavir and not shared by other PIs, it is easier to provide effective follow-up therapy to these individuals. This study showed that response to salvage therapy was associated with the genotype obtained at study entry, and that the L90 mutation portends a poorer response.
This article was provided by The Body PRO. Copyright © Body Health Resources Corporation. All rights reserved.