Impact of hepatitis C on HIV progression in adults with alcohol problems.

BACKGROUND: Coinfection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a substantial medical and public health concern due to its increasing prevalence and complex patient management. Alcohol use may worsen HCV-related liver disease and interfere with adherence to antiretroviral therapy (ART) and medical care. We therefore studied the association between HCV infection and markers of HIV disease progression in adults with alcohol problems. METHODS: This is a longitudinal study of 396 HIV-infected persons with alcohol problems, 199 (50%) of whom were coinfected with HCV (positive HCV RNA test). CD4 cell counts and HIV RNA levels were assessed at baseline and then every 6 months for up to 42 months. Hepatitis C virus RNA status was determined at study enrollment. We examined the relationship between HCV infection and laboratory markers of HIV progression (CD4 cell count and log10 HIV RNA) by fitting multivariable longitudinal regression models for each outcome. RESULTS: Among subjects who were adherent to ART, the presence of HCV infection was associated with a lower CD4 cell count (adjusted mean difference -46.0 cells/microL, p=0.03). There was no association observed between HCV infection and CD4 cell count among those not adherent to ART or those not taking ART. No significant association was observed between HCV infection and HIV RNA regardless of ART status. CONCLUSIONS: Hepatitis C virus infection has an adverse effect on CD4 cell count in patients with alcohol problems who are adherent to ART. Addressing HCV coinfection among these patients may confer additional immunologic benefit for this patient population.

Substance abuse treatment and receipt of liver specialty care among persons coinfected with HIV/HCV who have alcohol problems.

We examined the association of substance abuse treatment with access to liver specialty care among 231 persons coinfected with HIV and hepatitis C virus (HCV) with a history of alcohol problems who were recruited and followed up in the HIV-Longitudinal Interrelationships of Viruses and Ethanol cohort study from 2001 to 2004. Variables regarding demographics, substance use, health service use, clinical variables, and substance abuse treatment were from a standardized research questionnaire administered biannually. We defined substance abuse treatment services as any of the following in the previous 6 months: 12 weeks in a halfway house or residential facility, 12 visits to a substance abuse counselor or mental health professional, day treatment for at least 30 days, or any participation in a methadone maintenance program. Liver specialty care was defined as a visit to a liver doctor, a hepatologist, or a specialist in treating hepatitis C in the past 6 months. At study entry, most of the 231 subjects (89%, n = 205) had seen a primary care physician, 50% had been exposed to substance abuse treatment, and 50 subjects (22%) had received liver specialty care. An additional 33 subjects (14%) reported receiving liver specialty care during the follow-up period. In the multivariable model, we observed a clinically important although not statistically significant association between having been in substance abuse treatment and receiving liver specialty care (adjusted odds ratio = 1.38; 95% confidence interval = 0.9-2.11). Substance abuse treatment systems should give attention to the need of patients to receive care for prevalent treatable diseases such as HIV/HCV coinfection and facilitate its medical care to improve the quality of care for individuals with substance use disorders. The data illustrate the need for clinical care models that give explicit attention to the coordination of primary health care with addiction and hepatitis C specialty care while providing ongoing support to engage and retain these patients with complex health needs.

Barriers to treatment of hepatitis C in HIV/HCV-coinfected adults with alcohol problems.

BACKGROUND: Alcohol use and human immune deficiency virus (HIV) infection are both associated with accelerated progression of hepatitis C virus (HCV) disease and reduced response rates to interferon therapy. In this study, we assessed the prevalence of barriers to interferon treatment in a population of HIV/HCV-coinfected patients with current or past alcohol problems and the extent to which they received treatment to address the barriers. METHODS: This is a cross-sectional, descriptive analysis of baseline data from a prospective study assessing the impact of HCV and alcohol use on HIV disease progression. Using consensus guidelines, subjects were categorized as having absolute, relative, or no contraindications to interferon therapy for HCV. Absolute contraindications to treatment included heavy alcohol use, decompensated liver disease, CD4 cell count <100 cells/microL, recent needle sharing, and suicidal ideation. Relative contraindications included moderate alcohol use, recent injection drug use, depressive symptoms, and CD4 cell count from 100 to 199 cells/microL. RESULTS: Of 401 HIV-infected subjects, 200 were HCV RNA-positive. Fifty-three percent had an absolute contraindication to interferon therapy, 35% a relative but no absolute contraindication, and only 12% had no contraindication. Of those with an absolute contraindication, 61% reported heavy drinking and the majority (88%) had multiple contraindications. These contraindications were present despite the fact that over 50% were in receipt of substance abuse and mental health treatment. CONCLUSIONS: Continued alcohol and drug use as well as depressive symptoms are the major barriers to interferon therapy in HCV/HIV-coinfected subjects and these barriers persist despite high treatment rates for these problems. Therefore, more intensive treatments of alcohol, drug, and mental health issues are needed to improve HCV treatment eligibility in HCV/HIV-coinfected persons.

Hepatitis C infection is associated with depressive symptoms in HIV-infected adults with alcohol problems.

OBJECTIVES: Depression is common in persons with HIV infection and with alcohol problems, and it has important prognostic implications. Neurocognitive dysfunction has been reported with chronic hepatitis C virus (HCV) infection. We hypothesized that HCV infection is associated with more depressive symptoms in HIV-infected persons with a history of alcohol problems. METHODS: We performed a cross-sectional analysis of baseline data from a prospective cohort study of 391 HIV-infected subjects with a history of alcohol problems, of whom 59% were HCV antibody (Ab) positive and 49% were HCV RNA-positive. We assessed depressive symptoms (Center for Epidemiologic Studies Depression [CES-D]) and past month alcohol consumption. In the primary analysis, we evaluated whether there were more depressive symptoms in HCV Ab-positive and RNA-positive subjects in unadjusted analyses and adjusting for alcohol consumption, gender, age, race, CD4 count, homelessness, drug dependence, and medical comorbidity. RESULTS: Mean CES-D scores were higher in subjects who were HCV Ab-positive compared with those who were HCV Ab-negative (24.3 vs 19.0; p < 0.001). In adjusted analyses, the difference in CES-D scores between HCV Ab-positive and Ab-negative subjects persisted (24.0 vs 19.0; p < 0.001). Unadjusted mean CES-D scores were also significantly higher in HCV RNA-positive subjects compared with those who were RNA-negative, and the difference remained significant (24.6 vs 19.3; p < 0.001) in adjusted analyses. CONCLUSIONS: HCV/HIV coinfected persons with a history of alcohol problems have more depressive symptoms than those without HCV, and this association is unexplained by a variety of population characteristics. These data suggest that HCV may have a direct effect on neuropsychiatric function.

Assisted reproductive technology and pregnancy outcome.

OBJECTIVE: To determine whether the use of assisted reproductive technology (ART) is associated with an increase in chromosomal abnormalities, fetal malformations, or adverse pregnancy outcomes. METHODS: A prospective database from a large multicenter investigation of singleton pregnancies, the First And Second Trimester Evaluation of Risk trial, was examined. Subjects were divided into 3 groups: no ART use, use of ovulation induction (with or without intrauterine insemination), and use of in vitro fertilization (IVF). Multivariate logistic regression analysis was used to assess association between ART and adverse pregnancy outcomes (significance of differences was accepted at P < .05). RESULTS: A total of 36,062 pregnancies were analyzed: 34,286 (95.1%) were spontaneously conceived, 1,222 (3.4%) used ovulation induction, and 554 (1.5%) used IVF. There was no association between ART and fetal growth restriction, aneuploidy, or fetal anomalies after adjustment for age, race, marital status, years of education, prior preterm delivery, prior fetal anomaly, body mass index, smoking history, and bleeding in the current pregnancy. Ovulation induction was associated with a statistically significant increase in placental abruption, fetal loss after 24 weeks, and gestational diabetes after adjustment. Use of IVF was associated with a statistically significant increase in preeclampsia, gestational hypertension, placental abruption, placenta previa, and risk of cesarean delivery. CONCLUSION: Patients who undergo IVF are at increased risk for several adverse pregnancy outcomes. Although many of these risks are not seen in patients undergoing ovulation induction, several adverse pregnancy outcomes are still increased in this group. There was no increased incidence of fetal chromosomal or structural abnormalities in the women who used any type of ART compared with the women who conceived spontaneously. LEVEL OF EVIDENCE: II-2.

Quad screen as a predictor of adverse pregnancy outcome.

OBJECTIVE: To estimate the effect of second-trimester levels of maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), unconjugated estriol (uE3), and inhibin A (the quad screen) on obstetric complications by using a large, prospectively collected database (the FASTER database). METHODS: The FASTER trial was a multicenter study that evaluated first- and second-trimester screening programs for aneuploidy in women with singleton pregnancies. As part of this trial, patients had a quad screen drawn at 15-18 6/7 weeks. We analyzed the data to identify associations between the quad screen markers and preterm birth, intrauterine growth restriction, preeclampsia, and fetal loss. Our analysis was performed by evaluating the performance characteristics of quad screen markers individually and in combination. Crude and adjusted effects were estimated by multivariable logistic regression analysis. Patients with fetal anomalies were excluded from the analysis. RESULTS: We analyzed data from 33,145 pregnancies. We identified numerous associations between the markers and the adverse outcomes. There was a relatively low, but often significant, risk of having an adverse pregnancy complication if a patient had a single abnormal marker. However, the risk of having an adverse outcome increased significantly if a patient had 2 or more abnormal markers. The sensitivity and positive predictive values using combinations of markers is relatively low, although superior to using individual markers. CONCLUSION: These data suggest that components of the quad screen may prove useful in predicting adverse obstetric outcomes. We also showed that the total number and specific combinations of abnormal markers are most useful in predicting the risk of adverse perinatal outcome.

Preclinical and clinical performance of the Efoora test, a rapid test for detection of human immunodeficiency virus-specific antibodies.

Barriers to effective diagnostic testing for human immunodeficiency virus type 1 (HIV-1) infection can be reduced with simple, reliable, and rapid detection methods. Our objective was to determine the accuracy, sensitivity, and specificity of a new rapid, lateral-flow immunochromatographic HIV-1 antibody detection device. Preclinical studies were performed using seroconversion, cross-reaction, and interference panels, archived clinical specimens, and fresh whole blood. In a multicenter, prospective clinical trial, a four-sample matrix of capillary (fingerstick) whole-blood specimens and venous whole blood, plasma, and serum was tested for HIV-1 antibodies with the Efoora HIV rapid test (Efoora Inc., Buffalo Grove, IL) and compared with an enzyme immunoassay (EIA) (Abbott Laboratories) licensed by the Food and Drug Administration. Western blot and nucleic acid test supplemental assays were employed to adjudicate discordant samples. Preclinical testing of seroconversion panels showed that antibodies were often detected earlier by the rapid test than by a reference EIA. No significant interference or cross-reactions were observed. Testing of 4,984 archived specimens yielded a sensitivity of 99.2% and a specificity of 99.7%. A prospective multicenter clinical study with 2,954 adult volunteers demonstrated sensitivity and specificity for the Efoora HIV rapid test of 99.8% (95% confidence interval [CI], 99.3 and 99.98%) and 99.0% (95% CI, 98.5 and 99.4%), respectively. Reactive rapid HIV-1 antibody detection was confirmed in 99.6% of those with a known HIV infection (n = 939), 5.2% of those in the high-risk group (n = 1,003), and 0.1% of those in the low-risk group (n = 1,012). For 21 (0.71%) patients, there was discordance between the results of the rapid test and the confirmatory EIA/Western blot tests. We conclude that the Efoora HIV rapid test is a simple, rapid assay for detection of HIV-1 antibodies, with high sensitivity and specificity compared to a standardized HIV-1 EIA.

Impact of maternal age on obstetric outcome.

OBJECTIVE: To estimate the effect of maternal age on obstetric outcomes. METHODS: A prospective database from a multicenter investigation of singletons, the FASTER trial, was studied. Subjects were divided into 3 age groups: 1) less than 35 years, 2) 35-39 years, and 3) 40 years and older. Multivariable logistic regression analysis was used to assess the effect of age on outcomes after adjusting for race, parity, body mass index, education, marital status, smoking, medical history, use of assisted conception, and patient's study site. RESULTS: A total of 36,056 women with complete data were available: 28,398 (79%) less than 35 years of age; 6,294 (17%) 35-39 years; and 1,364 (4%) 40 years and older. Increasing age was significantly associated with miscarriage (adjusted odds ratio [adjOR]2.0 and 2.4 for ages 35-39 years and age 40 years and older, respectively), chromosomal abnormalities (adjOR 4.0 and 9.9), congenital anomalies (adjOR 1.4 and 1.7), gestational diabetes (adjOR 1.8 and 2.4), placenta previa (adjOR 1.8 and 2.8), and cesarean delivery (adjOR 1.6 and 2.0). Patients aged 35-39 years were at increased risk for macrosomia (adjOR 1.4). Increased risk for abruption (adjOR 2.3), preterm delivery (adjOR 1.4), low birth weight (adjOR 1.6), and perinatal mortality (adjOR 2.2) was noted in women aged 40 years and older. CONCLUSION: Increasing maternal age is independently associated with specific adverse pregnancy outcomes. Increasing age is a continuum rather than a threshold effect.

First-trimester maternal serum PAPP-A and free-beta subunit human chorionic gonadotropin concentrations and nuchal translucency are associated with obstetric complications: a population-based screening study (the FASTER Trial).

OBJECTIVE: The purpose of this study was to determine whether maternal serum levels of pregnancy-associated plasma protein A, free-beta subunit human chorionic gonadotropin, or nuchal translucency size are associated with obstetric complications. STUDY DESIGN: Data were obtained from the First and Second Trimester Evaluation of Risk trial. Pregnancy-associated plasma protein A and free-beta subunit human chorionic gonadotropin levels were analyzed, and nuchal translucency was measured between 10 weeks 3 days and 13 weeks 6 days of gestation in 34,271 pregnancies. RESULTS: Women with pregnancy-associated plasma protein A of < or =5th percentile were significantly more likely to experience spontaneous fetal loss at < or =24 weeks of gestation, low birth weight, preeclampsia, gestational hypertension, preterm birth ( P < .001) and stillbirth, preterm premature rupture of membranes, and placental abruption ( P < .02). Nuchal translucency at > or =99th percentile and free-beta subunit human chorionic gonadotropin at < or =1st percentile were associated with an increased risk of spontaneous loss at < or =24 weeks of gestation (adjusted odds ratios, 3.90, 3.62, respectively; P < .001). CONCLUSION: Low pregnancy-associated plasma protein A levels in the first trimester were associated strongly with a number of adverse pregnancy outcomes. Low free-beta subunit human chorionic gonadotropin levels and large nuchal translucency were both associated with early fetal loss.

Threatened abortion: A risk factor for poor pregnancy outcome, a population-based screening study.

OBJECTIVE: The purpose of this study was to determine whether patients with first-trimester threatened abortion are at increased risk for poor pregnancy outcome. STUDY DESIGN: A large prospective multicenter database was studied. Subjects were divided into three groups: (1) no bleeding, (2) light bleeding, and (3) heavy bleeding. Univariate and multivariable logistic regression analyses were used. RESULTS: The study comprised 16,506 patients: 14,160 patients without bleeding, 2094 patients with light bleeding, and 252 patients with heavy bleeding. Patients with vaginal bleeding, light or heavy, were more likely to experience a spontaneous loss before 24 weeks of gestation (odds ratio, 2.5 and 4.2, respectively) and cesarean delivery (odds ratio, 1.1 and 1.4, respectively). Light bleeding subjects were more likely to have preeclampsia (odds ratio, 1.5), preterm delivery (odds ratio, 1.3), and placental abruption (odds ratio, 1.6). Heavy vaginal bleeding subjects were more likely to have intrauterine growth restriction (odds ratio, 2.6), preterm delivery (odds ratio, 3.0), preterm premature rupture of membranes (odds ratio, 3.2), and placental abruption (odds ratio, 3.6). CONCLUSION: First-trimester vaginal bleeding is an independent risk factor for adverse obstetric outcome that is directly proportional to the amount of bleeding.

Interlaboratory comparison of fetal male DNA detection from common maternal plasma samples by real-time PCR.

BACKGROUND: Analysis of fetal DNA from maternal plasma by PCR offers great potential for noninvasive prenatal genetic diagnosis. To further evaluate this potential, we developed and validated a standard protocol to determine whether fetal DNA sequences could be reproducibly amplified and measured across multiple laboratories in a common set of specimens. METHODS: Each of five participating centers in a National Institute of Child Health and Human Development consortium collected 20 mL of peripheral blood from 20 pregnant women between 10 and 20 weeks of gestation. The plasma fraction was separated according to a common protocol, divided, and frozen in five aliquots. One aliquot was shipped to each participating laboratory, where DNA was extracted according to a standard protocol. All plasma samples (n = 100) were then analyzed blindly for the presence and quantity of total DNA (GAPDH) and male fetal DNA (SRY) by real-time PCR. Genomic DNA was isolated from female and male cells at one center, quantified, and shipped to the others to serve as calibrators for GAPDH and SRY, respectively. RESULTS: The amplification of known quantities of DNA was consistent among all centers. The mean quantity of male DNA amplified from maternal plasma when the fetus was male ranged from 51 to 228 genome equivalents (GE)/mL. Qualitative concordance was found overall among centers. The sensitivity of the assay for detection of male DNA when the fetus was male varied from 31% to 97% among centers. Specificity was more consistent (93-100%) with only four false-positive results obtained across the entire study. CONCLUSIONS: All centers were able to consistently amplify frozen and shipped DNA. The PCR procedure used here is reliable and reproducible. Centers that extracted and amplified more DNA per milliliter of maternal plasma had superior sensitivities of Y chromosome sequence detection. The specificity of the assay was more consistent among centers. A robust and thoroughly optimized protocol for the extraction of DNA from maternal plasma is needed to make testing of fetal DNA in maternal plasma a clinically relevant analytical tool.