Reference

A 48-week, randomized, open-label comparison of three abacavir-based substitution approaches in the management of dyslipidemia and peripheral lipoatrophy

A 48-week, randomized, open-label comparison of three abacavir-based substitution approaches in the management of dyslipidemia and peripheral lipoatrophy. Moyle, G. J.In this study， 136470-78-5 and 57-88-5 are also used.; Baldwin, C.; Langroudi, B.; Mandalia, S.; Gazzard, B. G. ( Chelsea and Westminster Hospital, London, UK). JAIDS, Journal of Acquired Immune Deficiency Syndromes, 33(1), 22-28 (English) 2003 Lippincott Williams & Wilkins. CODEN: JJASFJ. ISSN: 1525-4135. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) BACKGROUND: The mechanisms by which dyslipidemia and lipoatrophy develop during antiretroviral therapy are not clear. No treatment of lipoatrophy is currently established. METHODS: This was an open-label randomized study of HIV-pos. individuals on a first-line therapy contg. stavudine (d4T) with either a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) and with hypercholesterolemia (defined as total cholesterol >5.2 mmol/L or >180 mg/dL) and/or lipoatrophy and with a viral load of <50 copies/mL. Patients switched d4T to abacavir (ABC) (group 1), a PI or NNRTI to ABC (group 2), or d4T and PI or NNRTI to ABC plus AZT (group 3). Patients were followed-up with fasting blood levels, dual-energy X-ray absorptiometry (DXA), and computed tomog. (CT) scans for 48 wk. RESULTS: Thirty patients were included, with 27 completing 48 wk of therapy. One ABC hypersensitivity reaction was the only serious adverse event. All patients' viral loads remained at <50 copies/mL. CD4 cell counts rose in groups 2 and 3 but fell modestly in group 1. Total and low-d. lipoprotein cholesterol improved significantly in groups 2 and 3. Triglycerides fell significantly in group 2. In contrast, total, arm, and leg fat mass (by DXA) rose significantly in group 1 but fell modestly in groups 2 and 3. Visceral adiposity (by CT scan) was unaffected in all groups. CONCLUSIONS: Abacavir represents a virol. effective replacement for d4T, PI, or NNRTI in persons on successful first-line therapy. Replacement of a PI or NNRTI with ABC leads to modest improvement in both cholesterol and triglycerides. Replacement of d4T with ABC leads to modest improvements in fat mass. .

K65R with and without S68: a new resistance profile in vivo detected in most patients failing abacavir, didanosine and stavudine

K65R with and without S68: a new resistance profile in vivo detected in most patients failing abacavir, didanosine and stavudine. Roge, Birgit T.; Katzenstein, Terese L.; Obel, Niels; Nielsen, Henrik; Kirk, Ole; Pedersen, Court; Mathiesen, Lars; Lundgren, Jens; Gerstoft, Jan (Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, Den.). Antiviral Therapy, 8(2), 173-182 (English) 2003 International Medical Press. CODEN: ANTHFA. ISSN: 1359-6535. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Antiretroviral treatment with three nucleoside reverse transcriptase inhibitors (NRTIs) is widely used, but the combination of abacavir, didanosine and stavudine has never been investigated. We describe the surprising and consistent genotypic and phenotypic outcome in patients failing this combination. As part of a Danish multicentre study, 60 antiretroviral naive patients were randomized to treatment with abacavir, didanosine and stavudine. Failure was defined as one HIV-1 RNA >400 copies/mL.There are some reagents with their cas registry numbers 3056-17-5 and 136470-78-5 are used in this study. Genotyping was performed using TrueGene HIV-1 assay (Visible Genetics, London, UK). Phenotypic susceptibilities were detd. with the Virco Antivirogram assay. Eight patients failed treatment with a median viral load of 2.980 copies/mL (range 478-5.950). At baseline, five patients were wild-type. Three patients harbored nucleoside excision mutations (NEMs), but phenotypic susceptibilities were within normal range. All five patients with wild-type virus developed K65R and four of these patients also acquired the S68G mutation. Phenotypic susceptibility decreased towards abacavir (median 8.9-fold) and didanosine (median 3.2-fold), while susceptibility towards stavudine was unchanged (median 0.8-fold). Susceptibility towards lamivudine and tenofovir decreased median 14.2- and 4.0-fold, resp. In two patients with baseline resistance mutations, further accumulation of NEMs and V75T or L74V was obsd. One patient developed Q151 M. Failure of a triple NRTI regimen is possible and frequent with only the K65R mutation. Under adequate selection pressure K65R can easily emerge in vivo and may compromise several future treatment options including newer NRTIs. The unexpected high incidence of S68G suggests a functional role of this mutation in viruses harboring K65R. .