Diana Nurutdinova

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.

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.

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

Summary.  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, 1440 EIU) 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 <1000 copies/mL at the time of vaccination (P = 0.011) and male gender (P = 0.016). 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.

Routine screening for depression: identifying a challenge for successful HIV care

Individuals with HIV experience fluctuating levels of distress throughout the course of HIV infection. This study was conducted to examine the associations of depressive symptomatology with HIV disease in a cohort of individuals who are engaged in routine medical care. This cross-sectional study examined the prevalence of depressive symptoms that were measured as part of a standard of care behavioral assessment among individuals at an urban HIV clinic in the Midwest. Demographic characteristics, depressive symptoms, and behavioral risk factors were collected. A total of 514 individuals participated in the study, the majority of whom was male and African American. One quarter of the sample endorsed symptoms of other depressive disorder, while 18% (n = 91) endorsed symptoms of major depressive disorder as measured by the Patient Health Questionnaire-9 (PHQ-9). Among those on highly active antiretroviral therapy (HAART), individuals who were unemployed (adjusted odds ratio [AOR] = 2.47, 95% confidence interval [CI] = 1.54, 3.97), had a minor dependent (AOR = 2.17, 95% CI = 1.25, 3.77), or between the ages of 18 and 34 years (AOR = 1.37, CI = 1.03, 1.94) and detectable HIV viral load (AOR = 2.52, 95% CI = 1.22, 5.23) were more likely to report depressive disorder symptoms when controlling for age, gender, race, and education. Nearly 15% of the sample endorsed having suicidal thoughts at least once in the past two weeks. Regardless of HAART prescription, individuals who were unemployed had a higher likelihood of expressing suicidal ideation (AOR = 3.43, 95% CI = 1.66, 7.06). Given the association between depressive symptomatology and poor rates of HIV viral suppression, screening and appropriate interventions for depressive symptoms are warranted in the HIV outpatient setting to improve outcomes.

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.

Adverse Effects of Tenofovir Use in HIV-infected Pregnant Women and their Infants

Background: Data regarding use of tenofovir disopraxil 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 womans chart was reviewed for clinical data and adverse events during the pregnancy; each infants 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 m2 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-tote rated 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.

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.

Paragonimus kellicotti Fluke Infections in Missouri, USA

You don’t have to be a contestant on Fear Factor to eat unusual things. An investigation of 9 new cases of lung fluke infection in Missouri found that in all cases, patients had eaten raw crayfish while on rafting or camping trips and most had been drinking alcohol. Although all patients recovered after treatment, a few whose diagnosis was delayed had unnecessary procedures and serious illness. Physicians should consider lung fluke infection in patients with nonspecific cough and fever, especially patients who have recently returned from a recreational river trip. Crayfish in Missouri rivers often carry lung flukes and should not be eaten raw.

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.

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

BackgroundHepatitis 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.FindingsWe 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.ConclusionsThis 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.