A Case of Non-Cirrhotic Portal Hypertension Associated With Chronic Didanosine Therapy.

A 66-year-old man with HIV and recurrent thromboembolism presented with new-onset ascites with an extensive diagnostic work-up that was unremarkable. He was diagnosed with non-cirrhotic portal hypertension after a liver biopsy revealed mild fibrosis and hepatic venography revealed an elevated hepatic venous pressure gradient. The etiology of portal hypertension was attributed to didanosine therapy, a rare but noted side effect.

Efavirenz outperforms boosted atazanavir among treatment-naive HIV-1-infected persons in routine clinical care.

BACKGROUND: Effectiveness of antiretroviral therapy (ART) in a routine clinical care may result different from the clinical trials. We assessed the virologic outcomes in treatment-naive persons who received either efavirenz (EFV) or atazanavir/ritonavir (ATV/r) with a backbone of tenofovir/emtricitabine (TDF/FTC) as their combination ART (cART). METHODS: This was a retrospective cohort study conducted at the Washington University HIV Outpatient Clinic from January 2004 to June 2009. Predictors of virologic suppression (HIV RNA level <400 copies/mL) by week 48 were assessed by multivariate Cox proportional hazards regression models. RESULTS: Of 324 persons, 221(68%) received EFV and 103 (32%) received ATV/r. Persons on EFV had 1.4-fold increased likelihood of virologic suppression (95% confidence interval, 1.0-1.8) when compared to ATV/r after adjustment with primary drug resistance, pre-cART opportunistic infection, HIV RNA levels, and timing to start cART. CONCLUSIONS: In routine clinical care settings, EFV had higher likelihood of achieving virologic suppression than ATV/r with backbone of TDF/FTC.

Paragonimus kellicotti flukes in Missouri, USA.

Paragonimiasis is an infection caused by lung flukes of the genus Paragonimus. In Asia, P. westermani infections are relatively common because of dietary practices. However, in North America, cases of paragonimiasis, which are caused by P. kellicotti flukes, are rare. Only 7 autochthonous cases of paragonimiasis were reported during 1968-2008. In 2009, we reported 3 new case-patients with paragonimiasis who had been seen at our medical center over an 18-month period. Six additional case-patients were identified in St. Louis, Missouri, USA, and treated at Washington University-affiliated health centers in 2009-2010. We report detailed descriptions of these case-patients, which includes unusual clinical manifestations. We also describe public health interventions that were undertaken to inform the general public and physicians about the disease and its mode of transmission.

Transmitted drug-resistant HIV type 1 remains prevalent and impacts virologic outcomes despite genotype-guided antiretroviral therapy.

Trends in transmitted drug resistance-associated mutations (TDRM) in HIV-1infection vary depending on geographic and cohort characteristics. The impact of TDRM among patients receiving fully active combination antiretroviral therapy (cART) is poorly characterized. This was a retrospective study of 801 HIV-1-infected treatment-naive patients from 2001 to 2009 who had pre-cART genotype resistance test results available. The prevalence of TDRM was compared for each year strata. Multivariate Cox proportional hazards regression models were used to assess factors associated with virologic failure at 48 weeks. TDRM was detected in 136 (17%) patients with ≥2 class TDRM in 20 patients. K103N/S was the most frequent (n=77). There were no changes in the prevalence of mutations over time (P(trend)=0.67). Six hundred and eleven patients were started on cART. Virologic failure occurred in 38% of those with TDRM and 24% of those without (p<0.01). In multivariate analysis, nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance was associated with a 1.5-fold increased risk of virologic failure. TDRM remains common among treatment-naive HIV-1-infected patients, affecting one in six patients. Transmission of NNRTI drug resistance was associated with risk of virologic failure despite initiation of genotype-guided cART.

Mental health disorders and the risk of AIDS-defining illness and death in HIV-infected veterans.

OBJECTIVE: Mental health comorbidities are common in HIV-infected veterans and can impact clinical outcomes for HIV. We examined the impact of mental health diagnoses on progression to AIDS-defining illness (ADI) and death in a large cohort of HIV-infected veterans who accessed care between 2001 and 2006. DESIGN: Retrospective cohort study using the national Veterans Health Administration (VHA) HIV Clinical Case Registry. METHODS: We identified HIV-infected veterans initiating combination antiretroviral therapy (cART) within the VHA between 2000 and 2006. The prevalences of the following mental health diagnoses were examined: schizophrenia, bipolar disorder, depression, anxiety, and substance use disorder. Cox proportional hazards models were constructed to examine the relationship between mental health conditions and two outcomes, all-cause mortality and ADI. Models were computed before and after adjusting for confounding factors including age, race, baseline CD4 cell count, comorbidities and cART adherence. RESULTS: Among 9003 veterans receiving cART, 31% had no mental health diagnosis. Age, race, baseline comorbidity score, CD4, and cART adherence were associated with shorter time to ADI or death. All-cause mortality was more likely among veterans with schizophrenia, bipolar disorder and substance use, and ADI was more likely to occur among veterans with substance use disorder. CONCLUSIONS: Our results demonstrate the high prevalence of mental health diagnoses among HIV-infected veterans. In the era of highly active antiretroviral therapy, presence of psychiatric diagnoses impacted survival and development of ADI. More aggressive measures addressing substance abuse and severe mental illness in HIV-infected veterans are necessary.

Risk factors associated with Hepatitis C among female substance users enrolled in community-based HIV prevention studies.

BACKGROUND: Hepatitis C virus (HCV) infection is one of the most frequent chronic blood-borne infections in the United States. The epidemiology of HCV transmission is not completely understood, particularly in women and minorities. FINDINGS: We examined the HCV associated risk factors in substance abusing females involved in National Institute on Alcohol Abuse and Alcoholism (NIAAA) and National Institute on Drug Abuse (NIDA) funded HIV prevention studies of street recruited women. As a part of the 12 month follow-up, participants were interviewed about substance use and sexual risk behaviors, including drug implement sharing practices, tattoos, body piercing and blood transfusions and the sharing of personal hygiene equipment including tweezers, toothbrushes and razors. Urine and blood testing for HCV antibody (Ab), HIV and sexually transmitted diseases (STDs) was conducted at the time of assessment.Among 782 predominantly African American women, 162 (21%) tested positive for HCV Ab. Older age (p < 0.001), history of injection drug use (p < 0.001), lifetime crack cocaine use (p = 0.004) and having a tattoo (p = 0.01) were significantly associated with HCV Ab positivity. Other risk factors previously reported in association with HCV Ab positivity such as sexual risk behaviors were not significantly associated with the presence of a positive HCV Ab. CONCLUSIONS: This large community based sample of predominantly African American substance abusing women showed high prevalence of HCV Ab positivity and low awareness of their HCV serostatus. Our study demonstrated that in addition to intravenous drug use (IDU), other factors were significantly associated with HCV Ab positivity such as having a tattoo and a lifetime history of crack use. Other potential routes of HCV transmission should be further studied among high risk female populations.

Factors associated with receipt of adequate antidepressant pharmacotherapy by VA patients with recurrent depression.

OBJECTIVE: Adequate treatment of depression improves the prognosis of depressed individuals. This study identified sociodemographic, medical, psychiatric, and health care utilization factors associated with receipt of adequate antidepressant pharmacotherapy by Veterans Health Administration (VHA) patients with recurrent depression. METHODS: National VHA electronic medical records were used to construct a cohort of depressed patients who were experiencing a recurrent episode of depression between 1999 and 2006. Multinomial logistic regression determined factors that were associated with no receipt of treatment and with three levels of treatment: some antidepressant pharmacotherapy, adequate acute-phase pharmacotherapy, and adequate continuation-phase pharmacotherapy. RESULTS: A total of 26,770 patients aged 25 to 80 years, most of whom were male (84.5%), who were experiencing a recurrent episode of depression were identified. Female patients and those with substance abuse or dependence, nicotine dependence, or panic disorder were more likely to receive adequate acute-phase or continuation-phase treatment (or both) than to receive no treatment. Nonwhite race, being unmarried, having only VA benefits, having generalized anxiety disorder, and receiving treatment outside the mental health specialty sector were associated with a lower likelihood of receiving guideline-concordant care. CONCLUSIONS: Factors associated with receipt of adequate treatment for recurrent depression were similar to those found in previous studies for patients with new episodes of depression. This study was one of the first to focus specifically on patients experiencing recurrent depression, rather than combining patients with new and recurrent episodes in one sample. Continued research is warranted on how to modify factors to increase receipt of adequate care.

STD/HIV risk among adults in the primary care setting: are we adequately addressing our patients' needs?

BACKGROUND: Risk behavior surveys often target sexually transmitted disease (STD) clinic populations, but few studies address risk behaviors in primary care settings. METHODS: This cross-sectional study performed at a university adult primary care clinic evaluated risk behaviors using an anonymous, self-administered survey. The following data were collected: demographics, sexual history, condom use, and confidence discussing STDs. RESULTS: A total of 718 surveys were completed: 69% by females and 67% black. A total of 44% had never been asked about sexual health by their primary care provider and 18% reported they had never had a gender-specific genital examination. Among 394 sexually active individuals in the past 3 months, 58% reported never using a condom, and 33% stated they would not use a condom for their next sexual encounter. About one-third of the sample had never been tested for HIV and was not aware of their partner's HIV status. One-third reported history of STD, and 32% reported feeling uncomfortable discussing STDs with primary care provider. CONCLUSIONS: Our data demonstrate that sexual health is infrequently addressed despite high rates of previous STDs and low condom use in this population. Identifying barriers to determining sexual risk behaviors in the primary care setting will help to expand testing strategies for HIV and other STDs.

Rate of kidney function decline associates with mortality.

The effect of rate of decline of kidney function on risk for death is not well understood. Using the Department of Veterans Affairs national databases, we retrospectively studied a cohort of 4171 patients who had rheumatoid arthritis and early stage 3 chronic kidney disease (CKD; estimated GFR 45 to 60 ml/min) and followed them longitudinally to characterize predictors of disease progression and the effect of rate of kidney function decline on mortality. After a median of 2.6 years, 1604 (38%) maintained stable kidney function; 426 (10%), 1147 (28%), and 994 (24%) experienced mild, moderate, and severe progression of CKD, respectively (defined as estimated GFR decline of 0 to 1, 1 to 4, and >4 ml/min per yr). Peripheral artery disease predicted moderate progression of CKD progression. Black race, hypertension, diabetes, cardiovascular disease, and peripheral artery disease predicted severe progression of CKD. After a median of 5.7 years, patients with severe progression had a significantly increased risk for mortality (hazard ratio 1.54; 95% confidence interval 1.30 to 1.82) compared with those with mild progression; patients with moderate progression exhibited a similar trend (hazard ratio 1.10; 95% confidence interval 0.98 to 1.30). Our results demonstrate an independent and graded association between the rate of kidney function decline and mortality. Incorporating the rate of decline into the definition of CKD may transform a static definition into a dynamic one that more accurately describes the potential consequences of the disease for an individual.

The interplay of sociodemographic factors on virologic suppression among a U.S. outpatient HIV clinic population.

Understanding challenges to virologic suppression is essential to optimizing health outcomes among individuals with HIV. This cross-sectional behavioral assessment was conducted among 514 individuals presenting at an urban U.S. HIV clinic between June and September 2007. The majority of the sample was African American and male, with a mean age of 42 years. Most of the sample was receiving highly active antiretroviral therapy (HAART), and the majority of those had suppressed viral loads (HIV viral loads less than 400 copies per milliliter). By logistic regression analyses, African American/other minorities had 2.9 increased odds, those less than high school degree had 2.3 increased odds, those who were receiving ritonavir-boosted protease inhibitor therapy had 1.4 increased odds, and those who had expressed symptoms indicative of depressive disorders had 2.5 increased odds of having unsuppressed viremia as compared to Caucasians, those with more education, receiving non-nucleoside reverse transcriptase inhibitor-based therapy, and who had minimal depressive symptoms, respectively. These findings signify the importance of individualized interventions to enhance virologic suppression, both based on medication choices and individual characteristics.

A review of nucleoside reverse transcriptase inhibitor use to prevent perinatal transmission of HIV.

Worldwide, women comprise > 50% of all people living with HIV and the vast majority of these women are of childbearing age. In fact, a significant proportion of these women are identified as HIV-infected during pregnancy. Preventing perinatal transmission has been one of the greatest prevention successes of the HIV epidemic with < 2% of live births resulting in an HIV-infected infant. The strategic use of combination antiretroviral therapy has been a critical component of this reduction. With more antiretroviral agents available for HIV, the appropriate selection of therapy is often based on provider familiarity with the various agents. Although benefits of antiretroviral use in pregnancy tremendously outweigh the risks, concerns regarding short- and long-term toxicity in mothers and their children, in addition to the risk of the development of HIV resistance, remain subjects of discussion. The choice of antiretroviral 'backbone' is supported by extensive data showing efficacy in the prevention of HIV vertical transmission. Co-formulated zidovudine/lamivudine is the most commonly used combination in pregnancy. Long-term consequences of in utero exposure to antiretroviral agents are not fully understood. In this article, we review the data regarding nucleoside reverse transcriptase inhibitors with a focus on tenofovir.

Adverse effects of tenofovir use in HIV-infected pregnant women and their infants.

BACKGROUND: Data regarding use of tenofovir disoproxil fumarate in HIV-infected pregnant women are limited. OBJECTIVE: To identify adverse effects of tenofovir use during pregnancy in HIV-infected women and their infants. METHODS: In a retrospective case series, the charts of 127 pregnant HIV-infected women who received highly active antiretroviral therapy (HAART) between 2001 and 2005 were reviewed. Those who received tenofovir during pregnancy were selected for this study. Each woman's chart was reviewed for clinical data and adverse events during the pregnancy; each infant's chart was reviewed for growth parameters from birth to 12 months. RESULTS: Fifteen HIV-infected women with limited treatment options were prescribed HAART containing tenofovir during 16 pregnancies. In utero tenofovir exposure was a median of 127 days (range 6-259). Tenofovir was well tolerated by all women throughout pregnancy. There were 15 successful deliveries occurring at a median (range) of 36 weeks (30-40), with a median birth weight of 3255 g (1135-3610). Complications, including 1 spontaneous abortion, occurred in 9 pregnancies and were not attributed to tenofovir. Eleven (73%) women had abnormal laboratory results, including 6 who experienced grade 1 hemoglobin abnormalities; 4 of these women had preexisting anemia. Calculated glomerular filtration rate (calculated by Modification of Diet in Renal Disease equation) remained above 90 mL/min/1.73 m(2) in all women, except one who had a transient decline. Fourteen infants demonstrated normal growth and development for weight and height at birth, as well as during the 12-month follow-up period; no congenital malformations were documented. Mother-to-child transmission of HIV was not observed in this cohort. CONCLUSIONS: Tenofovir was found to be a well-tolerated component of HAART in this small cohort. Longer-term assessment of tenofovir effects on childhood growth and larger prospective studies of tenofovir use in pregnant women are warranted.

Effect of postpartum HIV treatment discontinuation on long-term maternal outcome.

BACKGROUND: Long-term maternal outcomes after postpartum antiretroviral therapy (ART) discontinuation are unknown. METHODS: Retrospective review of pregnancies in HIV-infected women on treatment between 1997 and 2005. Women were grouped by postpartum ART use and followed until new opportunistic infection (OI), death or last clinic visit. RESULTS: Of 172 pregnancies, postpartum ART discontinuation occurred in 123 (71.5%) women and was associated with greater parity, no partner during pregnancy, and no indication for OI prophylaxis or preconception ART in multivariate analysis (P < .05). Median follow-up was 32.5 months after delivery. There were 12 OIs and 2 deaths; 10 OIs and both deaths occurred in women who had discontinued ART. CONCLUSION: Postpartum ART discontinuation is common, especially among those with less advanced HIV disease, but may leave women at increased risk of long term adverse outcomes. This study highlights the need for larger longitudinal studies to determine appropriate recommendations for postpartum ART administration.

Incidence of sexually transmitted infections among HIV-infected women using depot medroxyprogesterone acetate contraception.

BACKGROUND: Previous studies suggest that depot medroxyprogesterone acetate (DMPA) is associated with an increased risk of sexually transmitted infection (STI) acquisition. The primary aim of this study was to characterize the potential association between DMPA use and risk of STI acquisition among HIV-infected women. STUDY DESIGN: This is a retrospective cohort study among HIV-infected women followed at a university clinic from 1997 to 2005. Medical records were reviewed for demographic data, HIV parameters, self-reported condom use, substance use, duration of follow-up and incident cases of gonorrhea, chlamydial infection and trichomoniasis. RESULTS: Of 304 HIV-infected women identified, 82 received DMPA and 222 did not. Overall incidence rates of trichomoniasis, chlamydial infection and gonorrhea were 8.4, 4.0 and 3.1 cases per 100 person-years, respectively, with no significant differences between the women receiving or not receiving DMPA. CONCLUSIONS: In this HIV-infected cohort, STI rates were higher than the general population, yet DMPA use did not appear to enhance the risk of STI acquisition. This latter finding suggests that the concern for STI acquisition should not be a limiting factor in the use of DMPA in HIV-infected women. The implementation of additional secondary prevention strategies remains an important focus in the HIV epidemic.