Structured treatment interruptions in antiretroviral management of HIV-1.

The consequences of treatment interruptions have been investigated in various patient populations. For patients with controlled viraemia, treatment interruption allowing viral rebound may boost HIV-1-specific immunity. The hypothesis that this will be sufficient to control HIV replication in the absence of treatment has received support in studies of patients initiating treatment during primary infections.

Mutational patterns in the HIV genome and cross-resistance following nucleoside and nucleotide analogue drug exposure.

A variety of key mutations in HIV reverse transcriptase (RT) have been associated with nucleoside reverse transcriptase inhibitor (NRTI) exposure, which give rise to a diverse range of effects in terms of altered drug susceptibilities, viral replicative capacity and RT biochemistry. There are three basic mechanisms of resistance conferred by specific mutations in the coding region of RT. The first is drug discrimination, whereby a particular drug or drugs are either selectively excluded from uptake or from the RT-primer-template catalytic complex.

International perspectives on antiretroviral resistance. Resistance to protease inhibitors.

The availability of protease inhibitors (PIs) and their combination with nucleoside reverse transcriptase inhibitors marked the passage of antiretroviral therapy (ART) from potential for control to effective suppression and thus substantially reduced rates of morbidity and mortality related to HIV. Even so, what was first hoped to be an immutable HIV DNA treatment target has proved to be prone to resistance mutations, with substitutions identified at more than 20 amino acid sites, which reduces PI susceptibility and increases resistance to treatment. The mutation patterns associated with each PI have been defined, and have been observed to occur at one of two locations: at or near the active site, or in the substrate cleavage site.

The impact of protease inhibitor-containing highly active antiretroviral therapy on progression of HIV disease and its relationship to CD4 and viral load.

Objective: To compare the rate of disease progression according to viral load and CD4 cell count in patients receiving or not receiving highly active antiretroviral therapy (HAART), defined as protease inhibitor-containing regimens.

Design: An observational study, with prospectively collected data.

Methods: All patients attending the HIV Outpatient clinic as of 1 January 1995 (n = 2083) were included.

HIV drug susceptibility and treatment response to mega-HAART regimen in patients from the Frankfurt HIV cohort.

Objective: To assess the relationship between viral susceptibility at baseline and virological response in human immunodeficiency virus (HIV)-infected patients treated with multi-drug salvage regimens after multiple previous treatment failures.

Design: Retrospective analysis of 50 patients from the Frankfurt HIV cohort who had received treatment with a minimum of six drugs, and for whom a sample for baseline viral phenotyping was available.

Methods: Viral drug susceptibility was measured retrospectively from stored samples using the Antivirogram, a recombinant virus assay based method.