Transmission cluster of multiclass highly drug-resistant HIV-1 among 9 men who have sex with men in Seattle/King County, WA, 2005-2007.

BACKGROUND: From 2005 through 2007, Seattle health care providers identified cases of primary multiclass drug-resistant (MDR) HIV-1 with common patterns of resistance to antiretrovirals (ARVs). Through surveillance activities and genetic analysis, the local Health Department and the University of Washington identified phylogenetically linked cases among ARV treatment-naive and -experienced individuals. METHODS: HIV-1 pol nucleotide consensus sequences submitted to the University of Washington Clinical Virology Laboratory were assessed for phylogenetically related MDR HIV. Demographic and clinical data collected included HIV diagnosis date, ARV history, and laboratory results. RESULTS: Seven ARV-naive men had phylogenetically linked MDR strains with resistance to most ARVs; these were linked to 2 ARV-experienced men. All 9 men reported methamphetamine use and multiple anonymous male partners. Primary transmissions were diagnosed for more than a 2-year period, 2005-2007. Three, including the 2 ARV-experienced men, were prescribed ARVs. CONCLUSIONS: This cluster of 9 men with phylogenetically related highly drug-resistant MDR HIV strains and common risk factors but without reported direct epidemiologic links may have important implications to public health. This cluster demonstrates the importance of primary resistance testing and of collaboration between the public and private medical community in identifying MDR outbreaks. Public health interventions and surveillance are needed to reduce transmission of MDR HIV-1.

Substituting abacavir for hyperlipidemia-associated protease inhibitors in HAART regimens improves fasting lipid profiles, maintains virologic suppression, and simplifies treatment.

BACKGROUND: Hyperlipidemia secondary to protease inhibitors (PI) may abate by switching to anti-HIV medications without lipid effects. METHOD: An open-label, randomized pilot study compared changes in fasting lipids and HIV-1 RNA in 104 HIV-infected adults with PI-associated hyperlipidemia (fasting serum total cholesterol >200 mg/dL) who were randomized either to a regimen in which their PI was replaced by abacavir 300 mg twice daily (n = 52) or a regimen in which their PI was continued (n = 52) for 28 weeks. All patients had undetectable viral loads (HIV-1 RNA <50 copies/mL) at baseline and were naive to abacavir and non-nucleoside reverse transcriptase inhibitors. RESULTS: At baseline, the mean total cholesterol was 243 mg/dL, low density lipoprotein (LDL)-cholesterol 149 mg/dL, high density lipoprotein (HDL)-cholesterol 41 mg/dL, and triglycerides 310 mg/dL. Mean CD4+ cell counts were 551 and 531 cells/mm3 in the abacavir-switch and PI-continuation arms, respectively. At week 28, the abacavir-switch arm had significantly greater least square mean reduction from baseline in total cholesterol (-42 vs -10 mg/dL, P < 0.001), LDL-cholesterol (-14 vs +5 mg/dL, P = 0.016), and triglycerides (-134 vs -36 mg/dL, P = 0.019) than the PI-continuation arm, with no differences in HDL-cholesterol (+0.2 vs +1.3 mg/dL, P = 0.583). A higher proportion of patients in the abacavir-switch arm had decreases in protocol-defined total cholesterol and triglyceride toxicity grades, whereas a smaller proportion had increases in these toxicity grades. At week 28, an intent-to treat: missing = failure analysis showed that the abacavir-switch and PI-continuation arms did not differ significantly with respect to proportion of patients maintaining HIV-1 RNA <400 or <50 copies/mL or adjusted mean change from baseline in CD4+ cell count. Two possible abacavir-related hypersensitivity reactions were reported. No significant changes in glucose, insulin, insulin resistance, C-peptide, or waist-to-hip ratios were observed in either treatment arm, nor were differences in these parameters noted between treatments. CONCLUSION: In hyperlipidemic, antiretroviral-experienced patients with HIV-1 RNA levels <50 copies/mL and CD4+ cell counts >500 cells/mm3, substituting abacavir for hyperlipidemia-associated PIs in combination antiretroviral regimens improves lipid profiles and maintains virologic suppression over a 28-week period, and it simplifies treatment.