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Interesting CROI Poster Highlights: nukes/RBV, CSF/HAART, 3-PI regimens, APV/Kaletra, single drug interruption, fitness
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Reported by David Margolis, MD, University of Texas, Southwestern Medical Center
In addition to nearly 175 oral presentations, more than 750 posters were presented at the 11th CROI. Although this is far more than can be absorbed in a few days, here are a few of the many interesting points:
- AZT, D4T, and 3TC were not significantly antagonized by ribavirin (Abstr. 136LB).
- The use of stable HAART containing multiple CSF penetrating drugs was did not increase the likelihood of a normal neuropsychological performance in a cross-sectional study. Only plasma HIV-1 viral load was independently associated with neuropsychological disorder (Abst. 508).
- In 20 HIV+ patients (2 females; mean age 41 years; median CD4 442 cells/mm3), SQV 1600 mg, RTV 100 mg, and ATV 300 mg once daily with a 20-g fat meal yielded adequate drug levels over 30 days of dosing (Abstr. 607).
- In 18 HIV+ patients (1 female; mean age 42 years) SQV 1000mg, RTV 200 mg, fosAPV 700 mg twice daily yielded adequate drug levels over 22 days of dosing. RTV 100 mg bid yields adequate levels in most patients, but SQV levels should be verified if 200 mg bid is not used (Abstr. 608).
- Pharmacokinetic parameters for LPV/r/APV are highly variable, and the magnitude of the interaction is unpredictable. LPV/r dose adjustments were more common than APV. Optimal management of the complex interaction between LPV/r and APV requires pharmacokinetically-guided dose individualization (Abst. 608-09, 611-12)
- Persistent, partial anti-HIV-1 activity of D4T despite NRTI resistance mutations was demonstrated by an increase in viremia during drug interruption. Patients with HIV-1 RNA >5000 copies/ml and CD4 cells >50/_L interrupted the D4T, DDI, or EFV component of their regimen while continuing the remaining drugs. Interruption of D4T for 14 days resulted in significant increases in HIV-1 RNA in 3/3 patients. By contrast, there was no significant increase in HIV-1 RNA in patients following interruption of EFV or DDI. The single drug interruption strategy may be useful for identifying combinations of drugs that still have activity even in heavily treatment-experienced patients (Abstr. 623).
- At 48 weeks in a randomized, open-label, multi-center study no differences were found in virological efficacy analyses between HIV-1-infected patients randomised to continue or discontinue 3TC in the new regimen after virological failure had occurred on a 3TC containing regimen (Abstr. 549).
- The fitness defect of NNRTI resistance mutants is small, but measurable in a culture system. The small magnitude of fitness loss is consistent with the persistence of NNRTI mutations in patient who have failed NNRTIs (abstr. 640).
- Using a reporter virus system, in which a fluorescent virus reporter is constructed using viral sequences from patients (similar to the Virologic phenotypic resistance assay) no fitness defect is detected in T-20 resistant viral isolates obtained from patients.
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