Thomas Campbell and colleagues report findings of a randomized trial conducted in multiple countries regarding the efficacy of antiretroviral regimens with simplified dosing.

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Functional immunologic assays using cryopreserved peripheral blood mononuclear cells (PBMC) are influenced by blood processing, storage and shipment. The objective of this study was to compare the viability, recovery and ELISPOT results of PBMC stored and shipped in liquid nitrogen (LN/LN) or stored in LN and shipped on dry ice (LN/DI) or stored at −70°C for 3 to 12 weeks and shipped on DI (70/DI 3 to 12); and to assess the effect of donor HIV infection status on the interaction between storage/shipment and the outcome measures. PBMC from 12 HIV-infected and 12 uninfected donors showed that LN/LN conferred higher viability and recovery than LN/DI or 70/DI 3, 6, 9 or 12. LN/DI PBMC had higher viability than any 70/DI PBMC. The PBMC viability and recovery linearly decreased with the duration of storage at −70°C from 3 to 12 weeks. This effect was more pronounced in samples from HIV-infected than uninfected donors. Results of ELISPOT assays using CMV pp65, CEF and Candida albicans antigens were qualitatively and quantitatively similar across LN/LN, LN/DI and 70/DI 3. However, ELISPOT values significantly decreased with the duration of storage at −70°C both in HIV-infected and uninfected donors. ELISPOT results also decreased with PBMC viability <70%.

High-density oligonucleotide arrays were used to determine the sequence of the protease (PR) and reverse transcriptase (RT) genes of human immunodeficiency virus type 1 isolates from 35 patients in whom combination therapy that included a protease inhibitor had failed. Isolates had a median of three PR mutations (range, none to six). Three isolates had no known resistance mutations in PR. Twelve isolates (34%) had two or fewer resistance mutations in PR. The most commonly observed PR mutations were L10I, V82A/T/F, and L90M. No mutations were observed at codons 30 or 48. Mutations at RT codons 215 and 184 were observed in the majority of isolates. These data suggest that therapy can fail in some patients with relatively few PR resistance mutations. Clinical failure in the absence of resistance mutations implies inadequate drug exposure due to pharmacologic factors or suboptimal patient adherence to drug therapy.