Search for Resistance in HIV/AIDS Clinical Care

Ongoing virologic monitoring, along with strict application of criteria for regimen switches, was associated with low rates of resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors, which in turn preserved second-line treatment options.

Most patients on second-line, protease inhibitor–based antiretroviral therapy had detectable viral loads, and half had evidence of triple-class resistance.

Resistance mutations were detected most frequently with AZT/3TC and during periods of low-level viremia.

Resistance-associated mutations were detected in 13.8% of treatment-naive patients in three Asian countries, but most of the mutations were of questionable clinical relevance.

Has the time come for ultrasensitive resistance testing?

Although available data are limited, a systematic review found no association between use of trimethoprim-sulfamethoxazole prophylaxis and increased resistance to other antibiotics.

Among patients initiating combination ART, the risk for virologic failure was three times higher among those whose regimens contained a drug they were resistant to than among those without resistance or those who initiated a fully active regimen despite resistance.

In patients with virologic failure, resistance to NNRTIs was more than twice as common as resistance to boosted PIs.

Women who receive antiretrovirals during pregnancy and then stop at delivery have a high rate of postpartum drug resistance.

Thirty-two percent of wild-type viruses have polymorphisms that diminish the activity of bevirimat, as do 45% of viruses from treatment-experienced patients with PI resistance.

Testing rates increased over time in two cohorts of HIV-infected patients but were low among women, heterosexuals, older patients, and blacks.

In a comparative clinical trial, patients receiving tenofovir/FTC were less likely to develop resistance mutations during virologic failure than were those receiving AZT/3TC.

HIV outpatients who underwent resistance testing were less likely to die than their untested counterparts during about 3 years of follow-up, but no single factor is likely to explain this observational finding.

Results from the MONARK trial do not support lopinavir/r monotherapy as first-line treatment for HIV infection, because it was both less effective and more likely to cause major PI resistance than triple therapy with lopinavir/r, AZT, and 3TC.

Among patients who experienced virologic rebound in this observational cohort study, risk for resistance was decreased in those who initiated ART at CD4 counts >350 cells/mm3.

An assay that measures HIV-derived DNA in peripheral blood mononuclear cells detected more resistance mutations in more patients than did standard serum resistance testing.

A study from Switzerland indicates that resistance rates might have actually decreased since 1999.

In a small study from Senegal, more than half of HIV-2–infected patients had genetic evidence of NRTI or PI resistance; specific mutations were dissimilar to those commonly seen with HIV-1.

Genotypic drug resistance is widespread following failure of initial therapy with NNRTIs but not with boosted PIs.

Low-frequency mutations are relatively common among treatment-naive patients and seem to influence outcome, but the more-sensitive assays to detect them aren’t yet ready for clinical use.