Journals
2009 EN
Steven C. Johnson
The appropriate time to initiate antiretroviral therapy (ART) for HIV infection is an area of much debate and some scientific study. In the absence of opportunistic infection, HIV-related symptoms, pregnancy, or comorbidities that may trigger the use of ART (e.g., hepatitis B), treatment guidelines have focused primarily on the CD4 lymphocyte count and plasma HIV RNA level and have suggested immunologic and virologic thresholds for the initiation of ART [1, 2]. These thresholds are an attempt to balance the benefits of therapy with the limitations of therapy, the major limitations being the development of drug resistance and/or drug toxicity. The rapid development of new antiretroviral agents and the results of recent clinical trials that support higher rates of efficacy and lower toxicity with contemporary treatment regimens have led to recent changes in treatment guidelines, including recommendations to initiate ART at somewhat higher CD4 cell counts [1, 2]. Recent data also suggest that earlier initiation of ART may be beneficial in pre-
Journals
2009 EN
J. Lucian Davis · Laurence Huang · Joseph A. Kovacs
+11 more
Nucleic acid amplification tests are sensitive and specific for identifying Mycobacterium tuberculosis in sputum smear-positive populations, but they are less sensitive in sputum smear-negative populations. Few studies have assessed their performance among patients infected with HIV, and no studies have assessed their performance with oral wash specimens, which may be easier to obtain than sputum samples.
Journals
2009 EN
Aaron A.R. Tobian · Blake Charvat · Victor Ssempijja
+12 more
Little is known about risk factors for incident herpes simplex virus type 2 (HSV-2) infection among men in Africa. In a trial in Rakai, Uganda, 6396 men aged 15-49 years were evaluated for serological evidence of HSV-2, human immunodeficiency virus (HIV), and syphilis infections at enrollment and at 6, 12, and 24 months. The prevalence of HSV-2 infection was 33.76%, and the incidence was 4.90 cases per 100 person-years. HSV-2 incidence increased with alcohol use with sexual intercourse (adjusted incidence rate ratio [adjIRR], 1.92 [95% confidence interval {CI}, 1.46-2.53]), decreased with consistent condom use (adjIRR, 0.56 [95% CI, 0.36-0.89]) and male circumcision (adjIRR, 0.70 [95% CI, 0.55-0.91]), and was not significantly affected by enrollment HIV status. Education on modifiable behavioral changes may reduce the acquisition of HSV-2. (ClinicalTrials.gov identifiers: NCT00425984 and NCT00124878 .).
Journals
2009 EN
Colleen F. Kelley · Christina M. Ramirez · Peter W. Hunt
+9 more
Although antiretroviral therapy has the ability to fully restore a normal CD4(+) cell count (>500 cells/mm(3)) in most patients, it is not yet clear whether all patients can achieve normalization of their CD4(+) cell count, in part because no study has followed up patients for >7 years.
Journals
2009 EN
Jay H. Hoofnagle · Abdus S. Wahed · Robert S. Brown
+2 more
Early changes in hepatitis C virus (HCV) RNA levels were assessed in a large cohort of African American and white patients with chronic hepatitis C due to HCV genotype 1 who underwent therapy with peginterferon alfa-2a and ribavirin in the Study of Viral Resistance to Antiviral Therapy of Hepatitis C (Virahep-C). Analyses were restricted to 341 patients who completed the first 28 days of therapy without dose modification. HCV RNA levels decreased in virtually all patients, but the amount of the change varied markedly. The overall 28-day decrease in HCV RNA levels was at least as predictive of a sustained virological response as the first- or second-phase viral kinetics responses. Factors associated with a smaller decrease in the HCV RNA level between baseline and day 28 included African American race, higher initial HCV RNA level, more severe hepatic fibrosis, and higher body weight. African American patients with similar 28-day decreases in viral levels as white patients were still less likely to achieve a sustained virological response. These results suggest that racial differences in the response to antiviral therapy are due to greater unresponsiveness to intracellular actions of interferon in African American individuals and that standard doses of peginterferon and ribavirin may be suboptimal for patients with higher body weights. Trial registration. ClinicalTrials.gov identifier: NCT00038974 .
Journals
2009 EN
Steven P. O’Hara · Aaron J. Small · Gabriella B. Gajdos
+3 more
Biliary cryptosporidiosis is associated with acquired immunodeficiency syndrome (AIDS) cholangiopathy and occurs almost exclusively in adult patients with AIDS. Infection of biliary epithelial cells (cholangiocytes) with Cryptosporidium parvum induces Toll-like receptor (TLR) 4 expression and stimulates a TLR-dependent response against infection. Here, we tested whether human immunodeficiency virus type 1 (HIV-1) Tat affects TLR expression and, hence, anti-C. parvum defense responses. Using an in vitro model of human biliary cryptosporidiosis, we found that recombinant Tat protein increased TLR4 mRNA expression in both uninfected and C. parvum-infected cholangiocytes. Conversely, Tat decreased TLR4 protein levels and suppressed C. parvum-induced TLR4 protein expression. Using actinomycin to inhibit transcription, we found that Tat increased the half-life of TLR4 mRNA from approximately 25 to 60 min, and RNA gel-shift assays demonstrated direct binding of Tat to TLR4 mRNA. In vitro transcription/translation studies suggested that Tat does not affect transcription but does decrease TLR4 translation. Importantly, more parasites were found in Tat-treated cells than in control cells 48 h after infection. These findings suggest that Tat inhibits cholangiocyte TLR4 protein expression through translational inhibition. These events appear to diminish the ability of cholangiocytes to initiate an innate immune response to C. parvum. We suggest that these findings may contribute to the unusual susceptibility of HIV-infected individuals to biliary cryptosporidiosis.
Journals
2009 EN
Wei Jiang · Michael M. Lederman · Peter W. Hunt
+10 more
The significance of elevated plasma levels of bacterial lipopolysaccharide (LPS) in persons with chronic HIV infection remains undefined. We measured LPS levels by use of limulus lysate assay, and DNA sequences encoding bacterial ribosomal 16S RNA (16S rDNA) were assessed by quantitative polymerase chain reactions in plasma samples obtained from 242 donors. Plasma levels of 16S rDNA were significantly higher in human immunodeficiency virus (HIV)-infected subjects than in uninfected subjects, and they correlated with LPS levels. Higher levels of 16S rDNA were associated with higher levels of T cell activation and with lower levels of CD4 T cell restoration during antiretroviral therapy. Antiretroviral therapy reduces but does not fully normalize plasma levels of bacterial 16S rDNA, an index of microbial translocation from the gastrointestinal tract. High levels of 16S rDNA during therapy are strongly associated with reduced increases in the CD4(+) T lymphocyte count, irrespective of plasma HIV RNA levels. These findings are consistent with the importance of microbial translocation in immunodeficiency and T cell homeostasis in chronic HIV infection.
Journals
2009 EN
Megan WindRotolo · Christine M. Durand · Lisa M. Cranmer
+15 more
Intrapartum single-dose nevirapine decreases mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but promotes nevirapine resistance. Although resistant viruses fade to undetectable levels in plasma, they may persist as stably integrated proviruses within the latent reservoir in resting CD4(+) T cells, potentially complicating future treatment.
Journals
2009 EN
Steven Y. C. Tong · Emma Bishop · Rachael A. Lilliebridge
+7 more
Some strains of non-multidrug-resistant, methicillin-resistant Staphylococcus aureus (nmMRSA) in Australia are likely to have emerged from strains of methicillin-susceptible S. aureus (MSSA) in remote Aboriginal communities.
Journals
2009 EN
Philip Sasi · Abdirahman I. Abdi · Leah Mwai
+14 more
In light of reports of increasing resistance of parasites to amodiaquine in African countries in which Plasmodium falciparum is endemic as well as the paucity of recent in vitro sensitivity data, we assessed the in vivo and in vitro sensitivity to amodiaquine of P. falciparum isolates from 128 pediatric outpatients (0.5-10 years old) in Pingilikani, Kilifi District, Kenya, who were treated with amodiaquine (10 mg/kg/day for 3 days). The polymerase chain reaction-corrected parasitological cure rate on day 28 (by Kaplan-Meier analysis) was 82% (95% confidence interval [CI], 74%-88%). Twenty-six percent (17/66) of tested pretreatment P. falciparum field isolates had 50% in vitro growth inhibition at concentrations of N-desethyl-amodiaquine (DEAQ)-the major biologically active metabolite of amodiaquine-above the proposed resistance threshold of 60 nmol/L, but baseline median DEAQ 50% inhibitory concentration values were not associated with subsequent risk of asexual parasite recrudescence (29 nmol/L [95% CI, 23-170 nmol/L] and 34 nmol/L [95% CI, 30-46 nmol/L] for patients with and those without recrudescences, respectively). The median absolute neutrophil count dropped by 1.3 X 10(3) cells/microL (95% CI, -1.7 X 10(3) to -0.7 X 10(3) cells/microL) between days 0 and 28. The high prevalence of in vitro and in vivo resistance precludes the use of amodiaquine on its own as second-line treatment. These findings also suggest that the value of amodiaquine combinations as first- or second-line treatment in areas with similar patterns of 4-aminoquinoline resistance should be reassessed.