David Haas

..015). Bacteremia was not associated with increased serum HIV-1 RNA levels. Thus, early MAC bacteremia is associated with increases in serum IL-6 levels, while TNF-alpha levels rise over time during advanced AIDS...

..Nelfinavir is a substrate for P-glycoprotein, which is encoded by MDR1. The present study examined associations between genetic variants and long-term responses to treatment...

..Rifampin is the cornerstone of antituberculosis therapy, but induction of hepatic cytochrome P4503A by rifampin markedly lowers HIV protease inhibitor plasma concentrations...

..We characterized associations between genetic polymorphisms and the pharmacokinetics of single doses of nevirapine and efavirenz...

..It is concluded with 95% confidence that phase 1 viral decay differences between exon 26 TT and CC groups are unlikely to exceed 18%...

..Defining cellular and tissue sources of HIV-1 in CSF is important for understanding disease pathogenesis and optimal therapies for HIV infection in the brain...

..Efavirenz is metabolized by cytochrome P4502B6 (CYP2B6). We investigated whether polymorphisms in CYP2B6, CYP3A4, CYP3A5, and MDR1 were associated with efavirenz central nervous system side effects and pharmacokinetics...

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..Among participants in a randomized study in South Africa (FTC-302), MDR1 3435C-->T was significantly associated with decreased risk of hepatotoxicity (risk ratio, 0.30; P=.016)...

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..011). Neutropenia, anemia, and drug intolerance were more common in the IFN-alpha group. This study demonstrates that IFN-alpha inhibits HIV-1 replication but attenuates the CD4+ cell response to dual therapy with ZDV and ddC...

..To compare the efficacy and safety of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine...

..This study supports the utility of ultraintensive CSF sampling for studying HIV-1 pathogenesis and therapy in the CNS, and provides strong evidence that HIV-1 RNA in CSF arises, at least in part, from a source other than plasma...

..023). Responses in efavirenz recipients were sustained at 48 weeks. Thus, efavirenz plus indinavir with concomitant NRTIs is effective therapy for NRTI-experienced patients...

..Low-dose ritonavir increases cerebrospinal fluid indinavir concentrations substantially more than 800 mg of indinavir given thrice daily without concomitant ritonavir, despite a lower total daily indinavir dose...

..Human DNA banks must allow future analyses while addressing confidentiality, ethical, and regulatory issues...

..Immune recovery during antiretroviral therapy is a complex phenotype that is influenced by multiple genetic variants. Future studies should validate these tentative associations and define underlying mechanisms...

..We examined whether long-term responses to efavirenz, and/or plasma efavirenz exposure, are better predicted by multilocus genetic interactions than by individual polymorphisms...

..Clinical stability has been observed with continued antiretroviral therapy (ART) in the setting of partial virological suppression. The optimal time to switch treatment in patients with low but detectable HIV-1 RNA is not known...

..Plasma F2-isoprostanes (F2-IsoP) reflect lipid peroxidation and oxidant stress and have been described in ART-associated toxicities. We explored factors associated with F2-IsoP in HIV-infected adults...

..Antiretroviral drug class did not independently predict P-gp activity...

..This article summarizes a presentation on HIV therapeutics and pharmacogenomics by David W. Haas, MD, at the International AIDS Society-USA course in Atlanta in March 2005...

..As inhibition of the PD-1/PD-L1 pathway is pursued as a therapeutic option for viral infections, potential effects of such a blockade on development of autoimmune responses in the CNS should be considered...

..Moreover, the ability to reprogram human T-cells into Treg cells in vitro will greatly aid in decoding their mechanism of suppression, their enhanced susceptibility to HIV infection, and the unique markers expressed by this subset...

..Mitochondria play a central role in regulating oxidant stress. We explored the relationships between oxidant stress and NRTI-induced peripheral neuropathy...

..Since iron deficiency is associated with some types of PN, and iron is essential for mitochondrial function, we tested the hypothesis that hemochromatosis (HFE) gene mutations influence susceptibility to NRTI-induced PN...

..Decreased risk of hepatotoxicity was associated with MDR1 3435C-->T (odds ratio, 0.254; P=.021). An interaction between MDR1 and hepatitis B surface antigen status predicted risk with 82% accuracy (P<.001)...

..The aim of our study was to characterize the effects of the P-glycoprotein substrate cyclosporin A on T cell P-glycoprotein activity in human immunodeficiency virus-infected participants in the AIDS Clinical Trials Group study A5138...

..Mitochondrial DNA (mtDNA) influences metabolic diseases and perhaps antiretroviral therapy (ART) complications. We explored associations between European mtDNA haplogroups and metabolic changes among A5142 participants...

..Penicillin resistance is rapidly increasing among S. pneumoniae isolates in Tennessee. The simultaneous detection of S. pneumoniae and high-level penicillin resistance can be accurately performed with the six-primer PCR assay...

..7 [95% confidence interval, 1.1-12.0]). An African mtDNA subhaplogroup is for the first time implicated in susceptibility to nucleoside reverse-transcriptase inhibitor-associated toxicity...

..Oxidant stress associated with therapeutic control of viral replication may have important implications for long-term complications of antiretroviral therapy...

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..The objective of this study was to determine if NRTI-associated peripheral neuropathy is associated with European mitochondrial haplogroups...

..Little is known about its utility in chronic inflammatory conditions such as HIV infection. We assessed relationships between hsCRP and metabolic parameters over time in HIV-infected patients on ART...

..This suggests an important role for HIV-specific CD8(+) T cells in control of intrathecal viral replication...

..Mitochondrial haplogroups and hemochromatosis gene (HFE) polymorphisms have been associated with ART-induced neuropathy. We assessed relationships between these variants and lipoatrophy...

..Determining the host factors within TEMRA cells that restrict R5-tropic viruses and endow HIV-1-specific CD4(+) T cells with this ability may result in novel therapeutic strategies against HIV-1 infection...

..Taken together, our findings indicate that CD4(+) NKT cells are directly targeted by HIV-1 and may have a potential role during viral transmission and spread in vivo...

..Our goal is to provide the infectious diseases specialist with information that will aid in the critical evaluation of publications that include human genomic analyses...

..Identifying factors associated with developing tuberculosis after HAART initiation could focus screening efforts...

..This TSLS outbreak in southeastern China was caused by a toxigenic clone of S. mitis. An apparently novel toxin may explain the unusual virulence of this organism...

..Advanced human immunodeficiency virus (HIV)-type 1 infection disrupts tonsillar architecture and depletes tonsillar lymphocytes. We tested whether HIV-1 infection reduces extracted human DNA yield from saliva...

..Although safe and generally well tolerated, 300 mg or 400 mg atazanavir administered every 12 h did not maintain adequate plasma exposure when coadministered with rifampin...

..Suppression to <400 viral RNA copies/mL was achieved at week 48 in 56% of patients with the D30N virus versus 18% of patients with the L90M virus...

..Baseline markers of immune activation and naive/memory lymphocyte subsets had limited ability to predict subsequent discordance...

..Total lymphocyte count also predicted a subsequent CD4(+) T cell change. These results document the utility of T cell markers in predicting treatment outcome and their potential value for the study and management of HIV-1 infection...

..CONCLUSION: In stably suppressed patients, 200 mg emtricitabine QD was equivalent to 150 mg lamivudine BID. Emtricitabine-containing HAART was associated with a high rate of sustained virologic suppression during 4 years of follow-up...

..Lower plasma efavirenz clearance is associated with a cytochrome P450 2B6 gene (CYP2B6) polymorphism (516G-->T) that is more frequent among African American individuals than among European American individuals...

..We propose that short-lived CD4+ T cells trafficking between the CNS and the periphery play an important role in amplifying and maintaining HIV-1 populations in the CNS during the asymptomatic phase of infection...

..Mutations remained detectable for at least 48 weeks in some subjects...

..Atazanavir (ATV) is a new PI with substantially less in vitro effect on glucose transport than observed with other PI, including lopinavir (LPV) or ritonavir (RTV)...

..Measures may include appropriate ventilation, outdoor seating, ultra-violet lights, and rapid on-site screening for tuberculosis...

..The proposed ACTU will not only enroll patients into ACTG clinical trials, but will provide the ACTG the ability to address important questions concerning AIDS treatment and pathogenesis. ..

..Characterizing these relationships will expand our knowledge regarding key events that lead to AIDS dementia, and may suggest novel approaches to other immunologic or viral-mediated diseases that affect the brain. ..

..Understanding how human genetic differences predict treatment response to HIV medications may help inform public health policy decisions about the safest and most effective use of antiretroviral regimens in the US and worldwide. ..