Stacey Chapman

Hepatic Steatosis Is Associated with Fibrosis, Nucleoside Analogue Use, and Hepatitis C Virus Genotype 3 Infection in HIV-Seropositive Patients

BACKGROUND We conducted a study to determine the prevalence and factors associated with hepatic steatosis in human immunodeficiency virus (HIV)-seropositive patients with hepatitis C and to investigate whether steatosis is associated with liver fibrosis. METHODS Retrospective chart reviews were conducted in 4 hospitals that serve community-based and incarcerated HIV-infected patients who had undergone a liver biopsy for evaluation of hepatitis C virus (HCV) infection during the period of 2000-2003. Demographic characteristics and medication and laboratory data were collected from the time of the biopsy. A pathologist blinded to all clinical data evaluated the specimens. The primary outcome was presence or absence of steatosis. RESULTS Of 260 HIV-HCV-coinfected patients, 183 met inclusion criteria and had a biopsy specimen adequate for review. Steatosis was present in 69% of patients (graded as minimal in 31%, mild in 27%, moderate in 18%, and severe in 1%). Factors associated with steatosis included use of dideoxynucleoside analogues, such as didanosine and stavudine (odds ratio [OR], 4.63; 95% confidence interval [CI], 1.55-13.82). There was a trend toward presence of steatosis and use of other nucleoside analogues or infection with HCV genotype 3 (OR, 2.65 [95% CI, 0.95-7.41] and 3.38 [95% CI, 0.86-13.28], respectively). The presence of steatosis was associated with fibrosis (OR, 1.37; 95% CI, 1.03-1.81). CONCLUSIONS In this multiracial population of HIV-HCV-coinfected patients, steatosis was prevalent and was associated with severity of liver fibrosis. Use of nucleoside analogues (particularly didanosine and stavudine) and HCV genotype 3 infection were associated with hepatic steatosis. The development of steatosis is multifactorial in nature and may play a contributory role in the progression of liver disease in HIV-infected patients.

Acute Hepatitis C Virus in an HIV Clinic: A Screening Strategy, Risk Factors, and Perception of Risk

Acute hepatitis C virus (HCV) infection is being acquired undetected among HIV-infected individuals. A practical way to regularly screen HIV-infected patients for acute HCV irrespective of perceived risk or symptoms is needed. We piloted implementation of an acute HCV screening strategy using routine HIV clinical care schedules and the least costly blood tests, in a Rhode Island HIV care center. Study participants had ongoing HCV risk, completed questionnaires encompassing risk behaviors and perception of risk, and were screened with quarterly alanine aminotransferase (ALT). ALT rise triggered HCV RNA testing, with pooled rather than individual specimen HCV RNA testing for underinsured participants. Participants were primarily older, college-educated men who have sex with men (MSM) with history of sexually transmitted infection other than HIV. One of 58 participants developed acute HCV in 50 person-years of observation for an annual incidence of 2.0% per year (95% confidence interval [CI] 0.05-11.1%). The majority (54%) of MSM did not perceive that traumatic sexual and drug practices they were engaging in put them at risk for HCV. Unprotected sex often occurred under the influence of drugs or alcohol. Self-reported HCV risk and participation in several risk behaviors declined during the study. It was possible to collect frequent ALTs in a busy HIV clinic with 71% of total projected ALTs obtained and 88% of participants having at least one ALT during the 9-month follow-up period. All instances of ALT rise led to reflexive HCV RNA testing. Tracking quarterly ALT for elevation to systematically prompt HCV RNA testing before seroconversion is a promising approach to screen for acute HCV in a real-world HIV clinical setting.

A Pilot Study of Treatment of Bacterial Vaginosis with a Buffering Vaginal Microbicide

BACKGROUND Bacterial vaginosis (BV) is an extremely common problem for women and is associated with adverse pregnancy outcomes and HIV infection. Currently available antibiotic treatments are moderately effective but may need to be repeated frequently because of the recurrent nature of the disease. We undertook a pilot study of a buffering vaginal microbicide in the treatment of BV. METHODS Women with clinically diagnosed BV were recruited to receive seven applications (5 g per application) of BufferGel trade mark (ReProtect, LLC, Baltimore, MD), a topical vaginal microbicide, and had clinical and gram stain evaluation of response. Subjects were evaluated at 2-3 days after the last application of BufferGel as a test of cure and again at 1 month to assess for relapse. Subjects with BV at test of cure were offered oral metronidazole. RESULTS Thirty-one women were screened, 16 were offered enrollment, and 10 completed the study. Treatment with BufferGel was clinically effective in 70% of women at 2-3 days after treatment and in 40% of women by 1-month follow-up. CONCLUSIONS These results suggest that 5 g of BufferGel vaginally once a day appears to be a moderately effective treatment for BV.

The spectrum of undiagnosed hepatitis C virus infection in a US HIV clinic.

United States guidelines endorse one-time HCV antibody screening at HIV diagnosis. Rescreening HCV-seronegative patients on a regular basis is still not policy, although HIV-infected persons have reasonably substantial HCV incidence. We evaluated routine risk factor-independent HCV antibody re-testing in a Rhode Island HIV clinic. We instituted annual HCV antibody testing for HCV-seronegative patients who had not been rescreened in a year or more. Testing based on clinical suspicion continued. We conducted a chart review of new antibody-positive cases in the first year of rescreening, July 2006 to June 2007. Of 245 rescreened patients, 11 (4.5%) seroconverted. Five (45%) were female. Median time between last negative and first positive result was 32 months (range 8-98 months). Six (55%) had documented risk factors and 6 (55%) elevated ALT (> 45  IU/L) between antibody tests; none prompted re-testing. One seroconverter died of hepatocellular carcinoma 3.7 years after HCV diagnosis. A twelfth was rescreened for suspected acute HCV based on ALT of 515  IU/L. He had newly detectable HCV RNA then seroconversion, and achieved SVR following 6 months of treatment in the acute phase for genotype 1 infection. Incident HCV is not uncommon among HIV-infected patients in care. Rescreening identified undiagnosed HCV in this population. HCV RNA should be checked promptly in HCV-seronegative persons with ALT elevation. We observed consequences of late diagnosis (hepatocellular carcinoma) and benefits of early diagnosis (cure with treatment of acute HCV). Adding annual rescreening to the Ryan White Program would facilitate earlier identification of undiagnosed HCV and create an instant widespread surveillance system, providing HCV incidence data.

Treatment for hepatitis C virus genotype 1 infection in HIV-infected individuals on methadone maintenance therapy

BACKGROUND A minority of HIV/HCV coinfected patients with opiate addiction undergo HCV treatment. HCV therapy for HCV-monoinfected methadone maintenance (MM) recipients is safe and effective. We evaluated treatment efficacy and adherence to pegylated interferon (pegIFN) among HIV/HCV coinfected MM recipients. METHODS HCV treatment-naïve, HIV-infected persons 18-65 years with chronic HCV genotype 1 on MM were prospectively enrolled in an HCV treatment study at two HIV clinics. At weekly visits pegIFN alfa-2a injections were directly administered. Daily MM recipients had morning ribavirin delivered with methadone at off-site methadone clinics. Weekly take-home MM recipients took ribavirin unsupervised. Target enrollment was 30 participants. RESULTS During 18 recruitment months, 11 participants were enrolled, 6 of whom received daily methadone. Mean age was 46, 64% were female, 5 were Caucasian, 4 Black and 2 Hispanic. At baseline, 82% had high HCV RNA and 55% had stage 2 fibrosis or greater. The majority (91%) were on HAART, and 82% had undetectable HIV RNA with a median CD4(+) of 508cells/μL. All had polysubstance use history, non-substance-based psychiatric diagnoses and were on psychotropic medications pre-enrollment. Two (18%) participants achieved a Sustained Virologic Response (SVR). Two completed 48 treatment weeks, 5 were withdrawn due to adverse events, 2 dropped out prematurely and 2 had treatment discontinued for virologic non-response. Of on-treatment weeks, adherence to pegIFN was >99%. CONCLUSIONS SVR rate was comparable to historic controls for coinfected genotype 1 patients, with optimal pegIFN adherence. Adverse effects often prevented therapy completion in this population.

Addition of Acyclovir does not affect Adherence to HAART in HIV-1/ HSV-2 Co-Infected Women.

1Alpert Medical School, Brown University, Providence, Rhode Island 2Center for the Statistical Sciences, Brown University, Providence, Rhode Island 3Miriam Hospital, Department of Medicine, Brown University, Providence, Rhode Island 4Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island, USA 5Department of Pathology and Laboratory Medicine, Emory University School of Medicine and Emory Center for AIDS Research, Atlanta, Georgia

Persistent genital tract HIV-1 RNA shedding after change in treatment regimens in antiretroviral-experienced women with detectable plasma viral load.

OBJECTIVE To longitudinally assess the association between plasma viral load (PVL) and genital tract human immunodeficiency virus (GT HIV) RNA among HIV-1 infected women changing highly active antiretroviral therapy (HAART) because of detectable PVL on current treatment. METHODS Women were eligible for the study if they had detectable PVL (defined as two consecutive samples with PVL>1000 copies/mL) and intended to change their current HAART regimen at the time of enrollment. Paired plasma and GT HIV-1 RNA were measured prospectively over 3 years. Longitudinal analyses examined rates of GT HIV-1 RNA shedding and the association with PVL. RESULTS Sixteen women were followed for a median of 11 visits contributing a total of 205 study visits. At study enrollment, all had detectable PVL and 69% had detectable GT HIV-1 RNA. Half of the women changed to a new HAART regimen with ≥3 active antiretroviral drugs. The probability of having detectable PVL ≥30 days after changing HAART was 0.56 (95% CI: 0.37 to 0.74). Fourteen women (88%) had detectable PVL on a follow-up visit ≥30 or 60 days after changing HAART; and 12 women (75%) had detectable GT HIV-1 RNA on a follow-up visit ≥30 or 60 days after changing HAART. When PVL was undetectable, GT shedding occurred at 11% of visits, and when PVL was detectable, GT shedding occurred at 47% of visits. CONCLUSIONS Some treatment-experienced HIV-infected women continue to have detectable virus in both the plasma and GT following a change in HAART, highlighting the difficulty of viral suppression in this patient population.

Effect of HSV-2 Suppressive Therapy on Genital Tract HIV-1 RNA Shedding among Women on HAART: A Pilot Randomized Controlled Trial

Background. The role of suppressive HSV therapy in women coinfected with HSV-2 and HIV-1 taking highly active antiretroviral therapy (HAART) is unclear. Methods. 60 women with HIV-1/HSV-2 coinfection on HAART with plasma HIV-1 viral load (PVL) ≤75 copies/mL were randomized to receive acyclovir (N = 30) or no acyclovir (N = 30). PVL, genital tract (GT) HIV-1, and GT HSV were measured every 4 weeks for one year. Results. Detection of GT HIV-1 was not significantly different in the two arms (OR 1.23, P = 0.67), although this pilot study was underpowered to detect this difference. When PVL was undetectable, the odds of detecting GT HIV were 0.4 times smaller in the acyclovir arm than in the control arm, though this was not statistically significant (P = 0.07). The odds of detecting GT HSV DNA in women receiving acyclovir were significantly lower than in women in the control group, OR 0.38, P < 0.05. Conclusions. Chronic suppressive therapy with acyclovir in HIV-1/HSV-2-positive women on HAART significantly reduces asymptomatic GT HSV shedding, though not GT HIV shedding or PVL. PVL was strongly associated with GT HIV shedding, reinforcing the importance of HAART in decreasing HIV sexual transmission.