Edgar Turner Overton

Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1

BACKGROUNDnThe combination of daclatasvir, a hepatitis C virus (HCV) NS5A inhibitor, and the NS5B inhibitor sofosbuvir has shown efficacy in patients with HCV monoinfection. Data are lacking on the efficacy and safety of this combination in patients coinfected with human immunodeficiency virus type 1 (HIV-1).nnnMETHODSnThis was an open-label study involving 151 patients who had not received HCV treatment and 52 previously treated patients, all of whom were coinfected with HIV-1. Previously untreated patients were randomly assigned in a 2:1 ratio to receive either 12 weeks or 8 weeks of daclatasvir at a standard dose of 60 mg daily (with dose adjustment for concomitant antiretroviral medications) plus 400 mg of sofosbuvir daily. Previously treated patients were assigned to undergo 12 weeks of therapy at the same doses. The primary end point was a sustained virologic response at week 12 after the end of therapy among previously untreated patients with HCV genotype 1 who were treated for 12 weeks.nnnRESULTSnPatients had HCV genotypes 1 through 4 (83% with genotype 1), and 14% had compensated cirrhosis; 98% were receiving antiretroviral therapy. Among patients with genotype 1, a sustained virologic response was reported in 96.4% (95% confidence interval [CI], 89.8 to 99.2) who were treated for 12 weeks and in 75.6% (95% CI, 59.7 to 87.6) who were treated for 8 weeks among previously untreated patients and in 97.7% (95% CI, 88.0 to 99.9) who were treated for 12 weeks among previously treated patients. Rates of sustained virologic response across all genotypes were 97.0% (95% CI, 91.6 to 99.4), 76.0% (95% CI, 61.8 to 86.9), and 98.1% (95% CI, 89.7 to 100), respectively. The most common adverse events were fatigue, nausea, and headache. There were no study-drug discontinuations because of adverse events. HIV-1 suppression was not compromised.nnnCONCLUSIONSnAmong previously untreated HIV-HCV coinfected patients receiving daclatasvir plus sofosbuvir for HCV infection, the rate of sustained virologic response across all genotypes was 97.0% after 12 weeks of treatment and 76.0% after 8 weeks. (Funded by Bristol-Myers Squibb; ALLY-2 ClinicalTrials.gov number, NCT02032888.).

Metabolic Syndrome in HIV-Infected Patients from an Urban, Midwestern US Outpatient Population

BACKGROUNDnThe association between the use of highly active antiretroviral therapy (HAART) and an increased risk of metabolic syndrome and cardiovascular disease remains unclear.nnnMETHODSnWe conducted a prospective, cross-sectional study of the risk factors associated with metabolic syndrome and cardiovascular disease among patients from an urban outpatient human immunodeficiency virus (HIV) clinic. Evaluation included laboratory data that were obtained after an overnight fast and a health survey that assessed traditional risk factors associated with cardiovascular disease, HIV-related factors, and comorbidities. Data collected were compared with data files from a cohort from the National Health and Nutrition Examination Survey (NHANES; 2001-2002) of persons who were seronegative for HIV infection who were matched for age, sex, race, and tobacco use.nnnRESULTSnFour hundred seventy-one HIV-infected subjects provided complete data. The overall prevalence of metabolic syndrome was similar between the group HIV-infected patients and the group of persons who were seronegative for HIV infection (25.5% vs. 26.5%, respectively), although the HIV-infected patients had a significantly smaller waist circumference, lower body mass index, lower high-density lipoprotein cholesterol levels, higher triglyceride levels, and lower glucose levels, compared with the subjects from the NHANES cohort. Framingham 10-year risk scores were also similar between the 2 groups. HIV-infected patients with metabolic syndrome were more likely to be diabetic, older, and white and have a high CD4 cell count and body mass index, compared with patients without metabolic syndrome (P<.05 for all). The type or duration of antiretroviral therapy was not an independent risk factor for metabolic syndrome.nnnCONCLUSIONSnThe prevalence of metabolic syndrome is high among HIV-infected persons, but not higher than the prevalence among HIV-uninfected persons. Traditional risk factors play a more significant role in the development of metabolic syndrome than do HIV treatment-associated factors.

Undetectable Plasma HIV RNA Load Predicts Success after Hepatitis B Vaccination in HIV-Infected Persons

Human immunodeficiency virus (HIV)-infected patients respond poorly to hepatitis B vaccination. Records of 194 HIV-infected patients were reviewed for factors associated with successful hepatitis B vaccination. Thirty-four patients (17.5%) developed a protective antibody response. In a logistic regression model, only a plasma HIV RNA level of <400 copies/mL at the time of vaccination was associated with a protective antibody response (P=.003).

Ongoing sexually transmitted disease acquisition and risk-taking behavior among US HIV-infected patients in primary care: implications for prevention interventions.

Background: To better understand the factors associated with HIV- and sexually transmitted disease (STD)-transmitting behavior among HIV-infected persons, we estimated STD prevalence and incidence and associated risk factors among a diverse sample of HIV-infected patients in primary care. Methods: We analyzed data from 557 participants in the SUN Study, a prospective observational cohort of HIV-infected adults in primary care in 4 US cities. At enrollment and 6 months thereafter, participants completed an audio computer-assisted self-interview about their sexual behavior, and were screened for genitourinary, rectal, and pharyngeal Neisseria gonorrhoeae and Chlamydia trachomatis infections by nucleic acid amplification testing, and for serologic evidence of syphilis. Women provided cervicovaginal samples and men provided urine to screen for Trichomonas vaginalis by polymerase chain reaction. Results: Thirteen percent of participants had a prevalent STD at enrollment and 7% an incident STD 6 months later. The most commonly diagnosed infections were rectal chlamydia, oropharyngeal gonorrhea, and chlamydial urethritis among the men and trichomoniasis among the women. Other than trichomoniasis, 94% of incident STDs were identified in men who have sex with men. Polysubstance abuse other than marijuana, and having ≥4 sex partners in the 6 months before testing were associated with diagnosis of an incident STD. Conclusions: STDs were commonly diagnosed among contemporary HIV-infected patients receiving routine outpatient care, particularly among sexually active men who have sex with men who used recreational drugs. These findings underscore the need for frequent STD screening, prevention counseling, and substance abuse treatment for HIV-infected persons in care.

Human papillomavirus infection and cytologic abnormalities of the anus and cervix among HIV-infected women in the study to understand the natural history of HIV/AIDS in the era of effective therapy (the SUN study).

Background: Human papillomavirus (HPV) infection of the cervix and related abnormal cervical cytology in HIV-infected women has been well described. Little is known about anal HPV infection in HIV-infected women. Methods: The SUN Study is a prospective cohort study of 700 HIV-infected patients including 167 women. At baseline, patients completed a behavioral questionnaire and provided, among other samples, cervical and anal swabs for HPV detection and genotyping and for cytologic examination. Here, we present the available baseline data on the 167 women in the SUN study. Results: Baseline results were available for 120 women (median age: 38 years, 57% non-Hispanic black, median CD4 cell count 444.5 cells/mm3), of whom, 77% were taking antiretroviral therapy. The prevalences in the anus and cervix of any HPV were 90% and 83%, respectively (P = 0.039), and of high-risk (HR) types 85% and 70%, respectively, (P = 0.001). There was no significant difference in the prevalences of abnormal cytology between the anus and cervix: 38% and 33%, respectively (P = 0.217). Although the presence of abnormal cervical cytology was associated with the presence of abnormal anal cytology (relative risk: 1.7, P = 0.024), its sensitivity (52.5%) and positive predictive value positive (45.6%) for identifying women with abnormal anal cytology were poor. A history of anal sex was not associated with anal HPV infection or abnormal anal cytology. Conclusions: In this cohort of HIV-infected women, anal HPV infection was more prevalent and diverse than cervical HPV infection. Anal cytologic abnormalities were as prevalent as cervical cytologic abnormalities, and although abnormal cervical cytology was predictive of abnormal anal cytology, results were not highly concordant. These data support the need for studies of anal cytologic screening of HIV-infected women.

Factors Associated with Prevalent Abnormal Anal Cytology in a Large Cohort of HIV-Infected Adults in the United States

BACKGROUNDnThe prevalence of and risk factors for abnormal anal cytology among men and women with human immunodeficiency virus (HIV) infection have not been extensively investigated.nnnMETHODSnThe Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN study) is a prospective cohort study of HIV-infected patients in 4 US cities. Baseline questionnaires were administered and anal samples for cytology and human papillomavirus (HPV) detection and genotyping were collected.nnnRESULTSnAmong 471 men and 150 women (median age, 41 years), 78% of participants were receiving combination antiretroviral therapy, 41% had a CD4(+) cell count of ≥500 cells/μL, and 71% had an HIV RNA viral load of <400 copies/mL. The anal cytology results were as follows: 336 participants (54%) had negative results, 96 participants (15%) had atypical squamous cells, 149 participants (24%) had low-grade squamous intraepithelial lesions, and 40 participants (6%) had high-grade squamous intraepithelial lesions. In a multivariate analysis, abnormal anal cytology was associated with number of high-risk and low-risk HPV types (adjusted odds ratio [AOR] for both, 1.28; P < .001), nadir CD4(+) cell count of <50 cells/μL (AOR, 2.38; P = .001), baseline CD4(+) cell count of <500 cells/μL (AOR, 1.75; P = .004), and ever having receptive anal intercourse (AOR, 2.51; P < .001).nnnCONCLUSIONnHIV-infected persons with multiple anal HPV types or a nadir CD4(+) cell count of <50 cells/μL have an increased risk for abnormal anal cytology.

Unrecognized chronic hepatitis C virus infection among baby boomers in the emergency department

The Centers for Disease Control and Prevention and U.S. Preventive Services Task Force have highlighted public screening as an essential strategy for increasing hepatitis C virus (HCV) detection in persons born between 1945 and 1965 (“baby boomers”). Because earlier HCV screening efforts have not targeted emergency department (ED) baby boomer patients, we describe early experience with integrated opt‐out HCV antibody (Ab) screening of medically stable baby boomers presenting to an urban academic ED. We performed HCV Ab testing 24 hours per day and confirmed positive test results using polymerase chain reaction (PCR). The primary outcome was prevalence of unrecognized HCV infection. Among 2,325 unique HCV‐unaware baby boomers, 289 (12.7%) opted out of HCV screening. We performed HCV Ab tests on 1,529 individuals, of which 170 (11.1%) were reactive. Among Ab reactive cases, follow‐up PCR was performed on 150 (88.2%), of which 102 (68.0%) were confirmed RNA positive. HCV Ab reactivity was more likely in males compared to females (14.7% vs. 7.4%; Pu2009<u20090.001), African Americans compared to whites (13.3% vs. 8.8%; Pu2009=u20090.010), and underinsured/ uninsured patients compared to insured patients (16.8%/16.9% vs. 5.0%; Pu2009=u20090.001). Linkage‐to‐care service activities were recorded for 100 of the 102 confirmed cases. Overall, 54 (54%) RNA‐positive individuals were successfully contacted by phone within five call‐back attempts. We confirmed initial follow‐up appointments for 38 (70.4%) RNA‐positive individuals successfully contacted, and 21 (55.3%) individuals with confirmed appointments attended their initial visit with a liver specialist; 3 (7.9%) are awaiting an upcoming scheduled appointment. Conclusion: We observed high prevalence of unrecognized chronic HCV infection in this series of baby boomers presenting to the ED, highlighting the ED as an important venue for high‐impact HCV screening and linkage to care. (Hepatology 2015;61:776–782)

Factors associated with renal dysfunction within an urban HIV-infected cohort in the era of highly active antiretroviral therapy

Kidney disease remains a prevalent problem in HIV care. The contribution of highly active antiretroviral therapy (HAART), HIV disease factors and traditional factors needs further evaluation.

Yoga lifestyle intervention reduces blood pressure in HIV-infected adults with cardiovascular disease risk factors*

People living with HIV infection are at increased risk for developing cardiovascular disease (CVD). Safe and effective interventions for lowering CVD risk in HIV infection are high priorities. We conducted a prospective, randomized, controlled study to evaluate whether a yoga lifestyle intervention improves CVD risk factors, virological or immunological status, or quality of life (QOL) in HIV‐infected adults relative to standard of care treatment in a matched control group.

Predictors of immunity after hepatitis A vaccination in HIV‐infected persons

Summary.u2002 Hepatitis A virus (HAV) infection remains a health risk for human immunodeficiency virus (HIV)‐infected persons. While the inactivated HAV vaccine affords protection to immunocompetent persons >95% of the time, rates of developing protective antibody (anti‐HAV) in HIV+ persons are considerably lower. Although low CD4+ T‐cell counts have previously been reported to be correlated with this poor response, the effect of HIV viraemia on HAV vaccine response has not previously been reported. The medical records of HIV‐infected patients who had received at least one dose of HAV vaccine (Havrix, 1440u2003EIU) were reviewed for factors associated with the development of a protective anti‐HAV response. Serological data with regard to anti‐HAV status after vaccination were available in 238 patients with 133 individuals (49.6%) developing immunity after vaccination. In a logistic regression model, the only factors associated with a protective antibody response were an HIV plasma RNA level <1000u2003copies/mL at the time of vaccination (Pu2003=u20030.011) and male gender (Pu2003=u20030.016). Neither nadir CD4+ T cell count nor CD4+ T‐cell count at time of vaccination were predictive of the development of anti‐HAV. Suppression of HIV replication at time of vaccination is associated with a protective antibody response to HAV vaccination in HIV‐infected adults. The low rate of response warrants further research in alternative strategies for HAV vaccination among HIV‐infected persons.