Development of HIV with Drug Resistance after CD4 Cell Count--Guided Structured Treatment Interruptions in Patients Treated with Highly Active Antiretroviral Therapy after Dual--Nucleoside Analogue Treatment

Feb 17, 2005Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

Development of drug-resistant HIV after treatment breaks based on CD4 counts in patients on advanced antiretroviral therapy following earlier dual-nucleoside treatment

AI simplified

PubMed ↗DOI ↗

Abstract

One major drug-resistance mutation occurred (T215Y) in 20 HIV-infected patients undergoing structured treatment interruption.

The study involved patients treated with highly active antiretroviral therapy (HAART) following dual nucleoside reverse-transcriptase inhibitor (NRTI) treatment.
Preexisting major mutations disappeared in four samples after treatment interruption.
Minor mutations in the HIV protease gene were present before treatment interruption and did not increase in frequency during the study.
The frequency of reverse-transcriptase gene mutations significantly decreased after structured treatment interruptions.
After 48 weeks, no patients experienced virological failure, with only one case of failure each in the STI and continuous treatment groups during long-term follow-up.

AI simplified

BACKGROUND: For patients with human immunodeficiency virus (HIV) infection, structured treatment interruption (STI) is an attractive alternative strategy to continuous treatment, particularly in resource-restrained settings, because it reduces both side effects and costs. One major concern, however, is the development of resistance to antiretroviral drugs that can occur during multiple cycles of starting and stopping therapy.

METHODS: HIV genotypic drug resistance was investigated in 20 HIV-infected Thai patients treated with highly active antiretroviral therapy (HAART) and CD4 cell count-guided STI after dual nucleoside reverse-transcriptase inhibitor (NRTI) treatment. Resistance was tested at the time of the switch from dual-NRTI treatment to HAART and when HAART was stopped during the last interruption.

RESULTS: After STI, one major drug-resistance mutation occurred (T215Y), and, in the 4 samples with preexisting major mutations (D67N [n=2], K70R [n=2], T215Y [n=2], and T215I [n=1]), the mutations disappeared. All mutations in the HIV protease gene were minor mutations already present, in most cases, before STI was started, and their frequency was not increased through STI, whereas the frequency of reverse-transcriptase gene mutations significantly decreased after the interruptions. After the 48-week study period, no patients had virological failure. Long-term follow-up (108 weeks) showed 1 case of virological failure in the STI arm and 1 in the continuous arm. No virological failure was seen in patients with major mutations.

CONCLUSIONS: Major HIV drug-resistance mutations were not induced through CD4 cell count-guided treatment interruptions in HIV-infected patients successfully treated with HAART after dual-NRTI therapy.

Full Text

Full text is available at the source.

View full text ↗

Abstract

Full Text

Related papers

what lands in your inbox each week: