Patterns of primary antiretroviral drug resistance in antiretroviral-naive HIV-1-infected individuals in a midwest university clinic.

A total of 192 HIV-1-infected antiretroviral-naive individuals had genotyping performed in our midwest university clinic between 2003 and 2005. The overall prevalence of resistance with either a reverse transcriptase or major protease mutation was 18%. There did not seem to be a significant difference in primary resistance patterns between different modes of HIV transmission (heterosexual versus men who have sex with men), gender or between white and African-American individuals.

Causative and contributive factors to asthma severity and patterns of medication use in patients seeking specialized asthma care.

STUDY OBJECTIVES: (1) To assess the prevalence of specific factors considered causative or contributive to asthma in a population of patients seen in a specialized asthma clinic, and to determine whether any of these factors were associated with more severe disease; and (2) to assess the utilization of inhaled steroids by asthma severity in this population and compare it with published guidelines of the National Heart, Lung, and Blood Institute (NHLBI). DESIGN, SETTING, AND PATIENT POPULATION: We conducted a retrospective chart review of new patients seen in a specialized asthma treatment center over a 2.5-year period and recorded the prevalence of 14 causative or contributive factors, the severity of asthma, and the intensity of treatment with inhaled corticosteroids in each patient. Patients were grouped as mild asthma vs moderate/severe asthma and compared by chi(2) analysis and stepwise logistic regression to determine whether certain factors were associated with more severe asthma. MEASUREMENTS AND RESULTS: The average number of factors recorded was 2.9 +/- 1.8 in the mild group (+/- SD) and 3.5 +/- 1.6 in the moderate/severe asthma group. This difference was statistically significant (p = 0.014). Increasing age, male gender, symptomatic gastroesophageal reflux disease (GERD), and chronic sinusitis were independently associated with more severe asthma. Suboptimal use of inhaled corticosteroids was more common in patients with mild persistent asthma, but suboptimal dosing of inhaled corticosteroids was equally common in mild and moderate/severe asthma. No relationship was found between allergen sensitization combined with exposure to cats, dogs, dust mite, or molds and more severe asthma. CONCLUSIONS: This study confirms earlier studies showing that symptomatic GERD and chronic sinusitis are important comorbid conditions in patients with asthma, both being associated with greater asthma severity. This study further shows that the doses of inhaled corticosteroids used for treatment of asthma fall short of NHLBI guidelines in the majority of patients regardless of asthma severity.

Efavirenz outperforms boosted atazanavir among treatment-naive HIV-1-infected persons in routine clinical care.

BACKGROUND: Effectiveness of antiretroviral therapy (ART) in a routine clinical care may result different from the clinical trials. We assessed the virologic outcomes in treatment-naive persons who received either efavirenz (EFV) or atazanavir/ritonavir (ATV/r) with a backbone of tenofovir/emtricitabine (TDF/FTC) as their combination ART (cART). METHODS: This was a retrospective cohort study conducted at the Washington University HIV Outpatient Clinic from January 2004 to June 2009. Predictors of virologic suppression (HIV RNA level <400 copies/mL) by week 48 were assessed by multivariate Cox proportional hazards regression models. RESULTS: Of 324 persons, 221(68%) received EFV and 103 (32%) received ATV/r. Persons on EFV had 1.4-fold increased likelihood of virologic suppression (95% confidence interval, 1.0-1.8) when compared to ATV/r after adjustment with primary drug resistance, pre-cART opportunistic infection, HIV RNA levels, and timing to start cART. CONCLUSIONS: In routine clinical care settings, EFV had higher likelihood of achieving virologic suppression than ATV/r with backbone of TDF/FTC.

Transmitted drug-resistant HIV type 1 remains prevalent and impacts virologic outcomes despite genotype-guided antiretroviral therapy.

Trends in transmitted drug resistance-associated mutations (TDRM) in HIV-1infection vary depending on geographic and cohort characteristics. The impact of TDRM among patients receiving fully active combination antiretroviral therapy (cART) is poorly characterized. This was a retrospective study of 801 HIV-1-infected treatment-naive patients from 2001 to 2009 who had pre-cART genotype resistance test results available. The prevalence of TDRM was compared for each year strata. Multivariate Cox proportional hazards regression models were used to assess factors associated with virologic failure at 48 weeks. TDRM was detected in 136 (17%) patients with ≥2 class TDRM in 20 patients. K103N/S was the most frequent (n=77). There were no changes in the prevalence of mutations over time (P(trend)=0.67). Six hundred and eleven patients were started on cART. Virologic failure occurred in 38% of those with TDRM and 24% of those without (p<0.01). In multivariate analysis, nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance was associated with a 1.5-fold increased risk of virologic failure. TDRM remains common among treatment-naive HIV-1-infected patients, affecting one in six patients. Transmission of NNRTI drug resistance was associated with risk of virologic failure despite initiation of genotype-guided cART.

Lopinavir-ritonavir: effects on endothelial cell function in healthy subjects.

To differentiate between the effects that antiretroviral drugs have on the endothelium and the secondary effects that they have on immune function, viral load, and dyslipidemia, 6 non-human immunodeficiency virus-infected human subjects were treated with lopinavir-ritonavir for 1 month and, on the basis of forearm blood flow, the treatment's effects on endothelial cell function were measured. Surprisingly, after exposure to lopinavir-ritonavir, absolute forearm blood-flow responses to the endothelium-dependent vasodilator, acetylcholine, increased significantly (P=.03), and forearm blood flow decreased to a greater extent during specific inhibition of NO synthase by N(G)-monomethyl-L-arginine. Thus, in this small cohort of subjects, short-term treatment with lopinavir-ritonavir does not appear to directly promote endothelial cell dysfunction.