Resistance Reporter > Volume 1, Issue 1: Resistance Reporter© from CROI 2007

Resistance Reporter

Section 1 (Section 2 Also Available)

Select presentations related to epidemiology of transmitted HIV drug resistance and effects of specific baseline resistance


Antiretroviral Drug-resistance Mutations and Subtypes in Drug-naive Persons Newly Diagnosed with HIV-1 Infection, US, March 2003 to October 2006

Poster# 648, Wheeler W (CDC)

Data from the Variant, Atypical and Resistant HIV Surveillance systems were used to estimate the prevalence of antiretroviral drug resistance mutations and to determine HIV-1 subtypes in this CDC study. Using specimens drawn from March 2003 to October 2006 from 409 sites in 11 states, RT and PR sequence data were identified from newly diagnosed, confidentially tested, and drug-naive persons. Major ARV drug resistance mutations were defined according to the International AIDS Society - USA guidelines, and HIV subtypes were derived using the Stanford online HIV Drug Resistance Database. Antiretroviral drug resistance mutations were observed in 10.4% of 3130 specimens, ranging from 6.3% to 13.0%. Drug resistance to nucleoside analog reverse transcriptase inhibitors (NRTIs) was found in 3.6%, to non-nucleoside reverse transcriptase inhibitors (NNRTIs) in 6.9%, and to protease inhibitors (PIs) in 2.4%. Multi-drug resistance mutations were noted in 1.9% of persons. Samples were overwhelmingly subtype B (94.9%). Most common other subtypes were C and CRF02_AG. The presence of resistance mutations in the non-B subtypes was not significantly different from the subtype B samples. See Oral Presentation 59, Schapiro, J, Impact of Subtype on HIV Drug Resistance for a discussion of the implications of non-B subtypes on HIV drug resistance.


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Transmission of HIV Drug Resistance and Treatment Response

Oral Presentation# 60, Little S

Transmitted Drug Resistance (TDR) in newly infected patients was in the range of 11-15%, above the threshold of 4-5% at which primary resistance testing is cost-effective. Genotypic testing is suggested for this population due to faster turnaround time. Little reported that resistant virus persisted about 2 years before there was any evidence of the emergence of wild type virus. Transmission of drug resistant virus was not associated with decreased replication capacity. Overall, patients with drug resistant virus at baseline (viral load at time of ART initiation) did not have viral loads significantly different from patients with wild type virus. However, there were significant differences depending on the drug class. Patients with NNRTI - resistant virus had significantly higher viral loads at initial evaluation , whereas those with NRTI -resistant virus had lower viral loads; those with PI - resistant virus had marginally lower viral loads. These effects persisted even after three years of follow up, except that VL differences among patients with PI-resistant virus disappeared over time . The study has been going on for just over 10 years (n=793). Little showed data from two subgroups: The first group contained those who initiated ART from 1995 to mid 2000 period; the second, those who initiated later. The earlier time period predated the recommendations for prospective drug resistance testing for patients with primary infection. Patients who were identified during this time period received on average a smaller number of active antiretroviral agents in their initial regimen. During the latter time period prospective resistance testing became standard of care. Patients treated during this latter period on average received a significantly larger number of active drugs than did the earlier group . The data presented showed only a trend for patients with resistant virus to take longer to achieve complete suppression. However, it is difficult to assess these results for two reasons: the disparity between patient groups in regards to prospective resistance testing, and the fact that regardless of time period most patients in this study started treatment with more than three active agents. See also CROI 2007 abstracts 648 above and 665, below.


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Baseline Resistance to NNRTI as a Predictor of Virologic Failure in Treatment-naïve Subjects Receiving Efavirenz-based Regimens in ACTG A5095

Poster# 665, Kuritzkes D

In ACTG5095, patients were randomized to receive either 2 or 3 NRTIs in addition to efavirenz (EFV). This sub-study analyzed those with treatment failure. They were compared to patients from the larger cohort, creating a case-cohort sample of 342 patients with analyzable data. The relative risk of virologic failure was compared in the presence or absence of baseline EFV resistance. In an analysis that adjusted for other risk factors including race/ethnicity and adherence, the presence of EFV resistance at baseline was associated with a 3.13 -fold increase in risk of virologic failure. All 13 subjects in the ZDV/3TC/EFV arm with EFV resistance at baseline experienced treatment failure. Interestingly, the only patients with EFV-resistant virus who did not experience virologic failure were patients who received EFV plus 3 NRTIs (n=3) . These findings support guidelines recommending resistance testing prior to initiating ART.


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