Drug resistant HIV: Behaviors and characteristics among Los Angeles men who have sex with men with new HIV diagnosis.

Epidemiology of drug resistant HIV has focused on trends and less attention has been given to identification of factors, especially behaviors including substance use, in acquisition of drug-resistant HIV. From 2009 to 2012 The Metromates Study enrolled and followed for one year men who have sex with men (MSM) seeking testing for HIV in a community clinic in Los Angeles assessing those testing positive for acute and recent HIV infection. Behavioral data were collected via Computer-Assisted Self-Interview from 125 classified as newly HIV infected and 91 as chronically infected (newly HIV-diagnosed); specimens were available and viable for resistance testing for 154 of the 216 HIV positives with new diagnoses. In this community clinic we found prevalence of resistance among MSM with new HIV-diagnosis was 19.5% (n = 30/154) with no difference by recency of HIV infection. Sexual partnership characteristics were associated with resistance; those who reported transgendered sex partners had a higher prevalence of resistance as compared to those who did not report transgendered sex partners (40% vs. 17%; p value = 0.04), while those who reported having a main partner had a lower prevalence of drug resistance (12% vs. 24%; p value = 0.07). In multivariable analyses adjusting for HIV recency and antiviral use, reporting a main partner decreased odds [adjusted odds ratio (AOR) 0.34; 95% confidence interval (CI) 0.13-0.87], reporting a transgendered partnered increased odds (AOR = 3.37; 95% CI 0.95-12.43); and being African American increased odds of drug resistance (AOR = 5.63, 95%CI 1.41-22.38). This suggests African American MSM and TG individuals in Los Angeles represent pockets of exceptional risk that will require special approaches to prevention and care to enhance their own health and reduce their likelihood to support transmission of drug resistance in the US.

Low prevalence of hepatitis C co-infection in recently HIV-infected minority men who have sex with men in Los Angeles: a cross-sectional study.

BACKGROUND: Geographic and sociodemographic characterization of hepatitis C virus (HCV) transmission amongst men who have sex with men (MSM) has been limited. Our aim was to characterize HCV prevalence, risk factors for HCV co-infection, and patterns of HIV and HCV co-transmission and transmitted drug resistance mutations (DRMs) in newly HIV-diagnosed Los Angeles MSM. METHODS: Viral RNA was extracted from stored plasma samples from a Los Angeles cohort of newly diagnosed HIV-infected MSM with well-characterized substance use and sexual behavioral characteristics via computer-assisted self-interviewing surveys. Samples were screened for HCV by qPCR. HCV E1, E2, core, NS3 protease and NS5B polymerase and HIV-1 protease and reverse transcriptase regions were amplified and sequenced. Phylogenetic analysis was used to determine relatedness of HCV and HIV-1 isolates within the cohort and viral sequences were examined for DRMs. RESULTS: Of 185 newly HIV-diagnosed MSM, the majority (65%) were of minority race/ethnicity and recently infected (57.8%), with median age of 28.3 years. A minority (6.6%) reported injection drug use (IDU), whereas 96 (52.8%) reported recent substance use, primarily cannabis or stimulant use. High risk sexual behaviors included 132 (74.6%) with unprotected receptive anal intercourse, 60 (33.3%) with group sex, and 10 (5.7%) with fisting. Forty-five (24.3%) had acute gonorrhea or chlamydia infection. Only 3 (1.6%) subjects had detectable HCV RNA. Amongst these subjects, HIV and HCV isolates were unrelated by phylogenetic analysis and none possessed clinically relevant NS3 or NS5B HCV DRMs. CONCLUSIONS: Prevalence of HCV co-infection was low and there was no evidence of HIV-HCV co-transmission in this cohort of relatively young, predominantly minority, newly HIV-diagnosed MSM, most with early HIV infection, with high rates of high risk sexual behaviors, STI, and non-IDU. The low HCV prevalence in a group with high-risk behaviors for non-IDU HCV acquisition suggests an opportune time for targeted HCV prevention measures.

The effect of hepatitis C virologic clearance on cardiovascular disease biomarkers in human immunodeficiency virus/hepatitis C virus coinfection.

BACKGROUND: Successful hepatitis C virus (HCV) treatment may reduce cardiovascular disease (CVD) risk and improve levels of CVD biomarkers produced outside the liver (nonhepatic biomarkers). METHODS: Stored serum or plasma from before and 24 weeks after end of HCV treatment (EOT) from human immunodeficiency virus (HIV)/HCV-coinfected subjects who received up to 72 weeks of peginterferon/ribavirin, 27 with and 27 without sustained virologic response (SVR) matched by race, ethnicity and sex, were tested for nonhepatic (soluble intercellular adhesion molecule-1 [sICAM-1], soluble P-selectin [sP-selectin], interleukin [IL]-6, d-dimer, and lipoprotein-associated phospholipase A2 [Lp-PLA2]) and hepatic (cholesterol and high-sensitivity C-reactive protein) CVD and macrophage activation markers (soluble CD163 [sCD163] and soluble CD14). Changes in biomarkers and their association with SVR were examined by t tests or Wilcoxon tests and regression models. RESULTS: Of the 54 subjects, 30 were white, 24 were black, and 44 were male. Pretreatment levels of nonhepatic biomarkers were high: sICAM-1 overall median, 439.2 ng/mL (interquartile range [IQR], 365.6-592.8]; sP-selectin, 146.7 ng/mL (IQR, 94.1-209.9), and IL-6, 2.32 pg/mL (IQR, 1.61-3.49). Thirty-seven of 52 (71%) subjects had Lp-PLA2 >235 ng/mL. Sustained virologic response was associated with decrease in sICAM-1 (P = .033) and sCD163 (P = .042); this result was attenuated after controlling for changes in the alanine aminotransferase level. At 24 weeks after EOT, 17 (63%) SVRs had Lp-PLA2 >235 ng/mL vs 25 (93%) non-SVRs (P = .021). CONCLUSIONS: Hepatitis C virus clearance may reduce hepatic and, subsequently, systemic inflammation and CVD risk in HIV/HCV coinfection.

Multiple disease-linked myotubularin mutations cause NFL assembly defects in cultured cells and disrupt myotubularin dimerization.

Charcot-Marie-Tooth disease (CMT) is an inherited peripheral neuropathy that has been linked to mutations in multiple genes. Mutations in the neurofilament light (NFL) chain gene lead to the CMT2E form whereas mutations in the myotubularin-related protein 2 and 13 (MTMR2 and MTMR13) genes lead to the CMT4B form. These two forms share characteristic pathological hallmarks on nerve biopsies including concentric sheaths ('onion bulbs') and, in at least one case, myelin loops. In addition, MTMR2 protein has been shown to interact physically with both NFL and MTMR13. Here, we present evidence that CMT-linked mutations of MTMR2 can cause NFL aggregation in a cell line devoid of endogenous intermediate filaments, SW13vim(-). Mutations in the protein responsible for X-linked myotubular myopathy (myotubularin, MTM1) also induced NFL abnormalities in these cells. We also show that two MTMR2 mutant proteins, G103E and R283W, are unable to form dimers and undergo phosphorylation in vivo, implicating impaired complex formation in myotubularin-related pathology.