HIV care and treatment settings provide an opportunity to reach people living with HIV/AIDS (PLHIV) with prevention messages and services. Population-based surveys in sub-Saharan Africa have identified HIV risk behaviors among PLHIV, yet data are limited regarding HIV risk behaviors of PLHIV in clinical care. This paper describes the baseline sociodemographic, HIV transmission risk behaviors, and clinical data of a study evaluating an HIV prevention intervention package for HIV care and treatment clinics in Africa. The study was a longitudinal group-randomized trial in 9 intervention clinics and 9 comparison clinics in Kenya, Namibia, and Tanzania (N = 3538). Baseline participants were mostly female, married, had less than a primary education, and were relatively recently diagnosed with HIV. Fifty-two percent of participants had a partner of negative or unknown status, 24% were not using condoms consistently, and 11% reported STI symptoms in the last 6 months. There were differences in demographic and HIV transmission risk variables by country, indicating the need to consider local context in designing studies and using caution when generalizing findings across African countries. Baseline data from this study indicate that participants were often engaging in HIV transmission risk behaviors, which supports the need for prevention with PLHIV (PwP).
HIV infection has been associated with development of prediabetes and diabetes. Optimum screening practices for these disorders in HIV-infected populations remain unclear.
We screened 377 adults, with- or at-risk for HIV infection, for incident hyperglycaemia (prediabetes or diabetes) using two oral glucose tolerance tests (OGTTs) a median of 18.6 months apart. We determined proportion of incident cases detected by fasting and 120-min plasma glucose levels. Independent predictors of incident hyperglycaemia were identified using logistic regression.
The baseline OGTT was consistent with diabetes in 7% of participants and with prediabetes in 31%. Among 352 normoglycaemic and prediabetic participants at baseline, 19 (5%) developed diabetes on follow-up. Among participants normoglycaemic at baseline, an additional 38 (16%) developed prediabetes. Overall 52% of incident hyperglycaemia cases were detected by fasting plasma glucose alone, 33% by a 120-min glucose level alone and 15% by both. Factors independently associated with incident hyperglycaemia included age ≥50 years and body mass index ≥30 kg/m2. Neither HIV infection nor highly active antiretroviral therapy (HAART) use were associated with increased risk of diabetes.
Incident hyperglycaemia is common among older adults with or at-risk for HIV infection. HIV-infected individuals with classic diabetes risk factors should be screened for hyperglycaemia regardless of HAART use. OGTTs may be the preferred screening strategy in HIV-infected individuals at high risk for developing hyperglycaemia.
Study Aims. Evaluate the quality and effectiveness of the medication-assisted therapy (MAT) pilot in Kazakhstan and review implementation context and related challenges. Methods. We performed a desk review of MAT policy and program documents and reviewed medical records at three MAT sites in Kazakhstan. MAT patients (n = 93) were interviewed to assess their perceptions of the program and its impact on their health, criminal, drug use, and HIV risk related behaviors as well as expenditures on nonprescribed psychoactive drugs. Persons injecting drugs who are not in treatment, MAT program staff, and other stakeholders were interviewed to obtain their perspectives on MAT. Results. Legislation supports introducing MAT as a standard of care for treatment of opioid dependence; however, its progress has been hampered by active opposition. Inadequate access and coverage, insufficient supply management, scarce infrastructure of narcological facilities, limited opportunities for staff development, and restrictive methadone dispensing policies compromise the quality of the intervention and limit its potential benefits. There were significant reductions in criminal, drug use, and HIV risk related behaviors in patients receiving MAT. Conclusions. The MAT pilot in Kazakhstan demonstrated its feasibility and effectiveness in the local context and is recommended for scaleup throughout the country.
Insulin-like growth factor (IGF) I stimulates the proliferation of hepatic stellate cells (HSC), the primary source of extracellular matrix accumulation in liver fibrosis. In contrast, insulin-like growth factor binding protein (IGFBP) 3, the most abundant IGFBP in circulation, negatively modulates HSC mitogenesis. To investigate the role of the IGF axis in hepatitis C virus (HCV)-related liver disease among high-risk patients, we prospectively evaluated HCV-viremic/HIV-positive women.
A cohort investigation.
Total IGF-I and IGFBP-3 were measured in baseline serum specimens obtained from 472 HCV-viremic/HIV-positive subjects enrolled in the Women's Inter-agency HIV Study, a large multi-institutional cohort. The aspartate aminotransferase to platelet ratio index (APRI), a marker of liver fibrosis, was assessed annually.
Normal APRI levels (< 1.0) at baseline were detected in 374 of the 472 HCV-viremic/HIV-positive subjects tested, of whom 302 had complete liver function test data and were studied. IGF-I was positively associated [adjusted odds ratio comparing the highest and lowest quartiles (AORq4–q1), 5.83; 95% confidence interval (CI) 1.17–29.1; Ptrend = 0.03], and IGFBP-3 was inversely associated (AORq4–q1, 0.13; 95% CI 0.02–0.76; Ptrend = 0.04), with subsequent (incident) detection of an elevated APRI level(> 1.5), after adjustment for the CD4 T-cell count, alcohol consumption, and other risk factors.
High IGF-I may be associated with increased risk and high IGFBP-3 with reduced risk of liver disease among HCV-viremic/HIV-positive women.
aspartate aminotransferase to platelet ratio index; APRI; hepatitis C virus (HCV); HIV; IGFBP-3; IGF; liver disease
Opiate use is common in HIV- and hepatitis C virus (HCV)-infected individuals, however its contribution to the risk of diabetes mellitus is not well understood.
Prospective study of 1,713 HIV-infected and 652 uninfected participants from the Women’s Interagency HIV Study between October 2000 and March 2006. Diabetes defined as fasting glucose ≥126 mg/dl, or self-report of diabetes medication use or confirmed diabetes diagnosis. Opiate use determined using an interviewer-administered questionnaire. Detectable plasma HCV RNA confirmed HCV infection.
Current opiate users had a higher prevalence of diabetes (15%) than non-users (10%, p=.03), as well as a higher risk of incident diabetes (adjusted relative hazard [RHadj] 1.58, 95% CI 1.01, 2.46), after controlling for HCV infection, HIV/antiretroviral therapy status and diabetes risk factors including age, race/ethnicity, family history of diabetes and body mass index. HCV infection was also an independent risk factor for diabetes (RHadj 1.61, 95% CI 1.02, 2.52). HCV-infected women reporting current opiate use had the highest diabetes incidence (4.83 cases/100 person-years).
Among women with or at-risk for HIV, opiate use is associated with increased diabetes risk independently of HCV infection. Diabetic screening should be part of care for opiate users, and those infected with HCV.
opiate use; diabetes mellitus; fasting glucose; Hepatitis C virus; HIV; women
Limited data suggest that glycated hemoglobin (hemoglobin A1c; A1C) values may not reflect glycemic control accurately in HIV-infected individuals with diabetes.
We evaluated repeated measures of paired fasting glucose and A1C values in 315 HIV-infected and 109 HIV-uninfected diabetic participants in the Women's Interagency HIV Study. Generalized estimating equations used log A1C as the outcome variable, with adjustment for log fasting glucose concentration in all models.
An HIV-infected woman on average had 0.9868 times as much A1C (that is, 1.32% lower; 95% confidence interval 0.9734-0.9904) as an HIV-uninfected woman with the same log fasting glucose concentration. In multivariate analysis, HIV serostatus was not associated, but white, other non-black race, and higher red blood cell mean corpuscular volume (MCV) were statistically associated with lower A1C values. Use of diabetic medication was associated with higher A1C values. In multivariate analysis restricted to HIV-infected women, white and other race, higher MCV, and HCV viremia were associated with lower A1C values whereas older age, use of diabetic medications and higher CD4 cell count were associated with higher A1C values. Use of combination antiretroviral therapy, protease inhibitors, zidovudine, stavudine, or abacavir was not associated with A1C values.
We conclude that A1C values were modestly lower in HIV-infected diabetic women relative to HIV-uninfected diabetic women after adjustment for fasting glucose concentration. The difference was abrogated by adjustment for MCV, race, and diabetic medication use. Our data suggest that in clinical practice A1C gives a reasonably accurate refection of glycemic control in HIV-infected diabetic women.
Persons who use illicit drugs are at increased risk of new tuberculosis (TB) infection. We conducted a prospective cohort study to assess rates and risk factors for tuberculin skin test (TST) conversion among persons with a history of illicit drug use, who were enrolled in a methadone program and had a negative baseline 2-step TST (eligible participants).
TST and standardized interviews were administered to 401 eligible participants from 1995 through 1999, every 6 months for a 2-year follow-up time. Analyses were conducted in 2006.
A total of 1,447 repeat TSTs were performed during 843 person-years of follow-up (median: 2.0 years). The TST conversion rate was 3.7 per 100 person-years. In multivariate analysis, participants who converted were more likely to report ever having been homeless (HR, 2.4; 95% CI, 1.2–5.0) or ever having lived in a homeless shelter (HR, 2.4; 95% CI, 1.2–4.9) at the baseline interview, and less likely to have reported receiving public assistance since the last study visit (RR, 0.15; 95% CI, 0.07–0.32).
This is the first study utilizing 2-step TST at baseline to measure the incidence of TST conversion among persons who use illicit drugs. Controlling for homelessness, persons with a lack of current public assistance was identified as a risk factor for TST conversion. These individuals may most benefit from annual tuberculin skin testing.
substance use; tuberculin skin test; tuberculosis; urban; New York City
To determine the association of self-perceived fat gain or fat loss in central and peripheral body sites with adherence to highly active antiretroviral therapy (HAART) in HIV-seropositive women. 1,671 women from the Women’s Interagency HIV Study who reported HAART use between April 1999 and March 2006 were studied. Adherence was defined as report of taking HAART ≥ 95% of the time during the prior 6 months. Participant report of any increase or decrease in the chest, abdomen, or upper back in the prior 6 months defined central fat gain and central fat loss, respectively. Report of any increase or decrease in the face, arms, legs or buttocks in the prior 6 months defined peripheral fat gain or peripheral fat loss. Younger age, being African-American (vs. White non-Hispanic), a history of IDU, higher HIV RNA at the previous visit, and alcohol consumption were significant predictors of HAART non-adherence (P <0.05). After multivariate adjustment, self-perception of central fat gain was associated with a 1.5-fold increased odds of HAART non-adherence compared to no change. Perception of fat gain in the abdomen was the strongest predictor of HAART non-adherence when the individual body sites were studied. Women who perceive central fat gain particularly in the abdomen are at risk for decreased adherence to HAART despite recent evidence to suggest that HIV and specific antiretroviral drugs are more commonly associated with fat loss than fat gain.
Lipodystrophy; HIV; Women; HAART adherence; body image perception
Hazardous alcohol consumption among women with human immunodeficiency virus (HIV) infection is associated with several adverse health and behavioral outcomes, but the proportion of HIV-positive women who engage in hazardous drinking over time is unclear. The authors sought to determine rates of hazardous alcohol consumption among these women over time and to identify factors associated with this behavior. Subjects were 2,770 HIV-positive women recruited from 6 US cities who participated in semiannual follow-up visits in the Women's Interagency HIV Study from 1995 to 2006. Hazardous alcohol consumption was defined as exceeding daily (≥4 drinks) or weekly (>7 drinks) consumption recommendations. Over the 11-year follow-up period, 14%–24% of the women reported past-year hazardous drinking, with a slight decrease in hazardous drinking over time. Women were significantly more likely to report hazardous drinking if they were unemployed, were not high school graduates, had been enrolled in the original cohort (1994–1995), had a CD4 cell count of 200–500 cells/mL, were hepatitis C-seropositive, or had symptoms of depression. Approximately 1 in 5 of the women met criteria for hazardous drinking. Interventions to identify and address hazardous drinking among HIV-positive women are urgently needed.
alcohol drinking; HIV; longitudinal studies; women
Longitudinal associations between patterns of crack cocaine use and progression of human immunodeficiency virus (HIV-1) disease are poorly understood, especially among women. This paper explores relationships between crack use and HIV-1 disease outcomes in a multi-center cohort of infected women.
Subjects were 1686 HIV-seropositive women enrolled at six U.S. research centers in the Women’s Interagency HIV Study. Approximately 80% were nonwhite and 29% used crack during the study period. Cox survival and random regression analysis examined bi-annual observations made April 1996 through September 2004. Outcome measures included: death due to AIDS-related causes; CD4 cell count; HIV-1 RNA level; and newly acquired AIDS-defining illnesses.
Persistent crack users were over three times as likely as nonusers to die from AIDS-related causes, controlling for use of highly active antiretroviral viral therapies self-reported at >=95% adherence, problem drinking, age, race, income, education, illness duration, study site, and baseline virologic and immunological indicators. Persistent crack users and intermittent users in active phases showed greater CD4 cell loss and higher HIV-1 RNA levels controlling for the same covariates. Persistent and intermittent crack users were more likely than nonusers to develop new AIDS-defining illnesses controlling for identical confounds. These results persisted when controlling for heroin use, tobacco smoking, depressive symptoms, Hepatitis C virus co-infection, and intravenous drug use.
Use of crack cocaine independently predicts AIDS-related mortality, immunologic and virologic markers of HIV-1 disease progression, and development of AIDS-defining illnesses among women.
To compare electronically monitored (MEMS) with self-reported adherence in drug users, including the impact of adherence on HIV load, we conducted a 6-month observational study of 67 antiretroviral-experienced current and former drug users. Adherence (percentage of doses taken as prescribed) was calculated for both the day and the week preceding each of 6 research visits. Mean self-reported 1-day adherence was 79% (median, 86%), and mean self-reported 1-week adherence was 78% (median, 85%). Mean MEMS 1-day adherence was 57% (median, 52%), and mean MEMS 1-week adherence was 53% (median, 49%). One-day and 1-week estimates were highly correlated (r> .8 for both measures). Both self-reported and MEMS adherence were correlated with concurrent HIV load (r=.43–.60), but the likelihood of achieving virologic suppression was greater if MEMS adherence was high than if self-reported adherence was high. We conclude that self-reported adherence is higher than MEMS adherence, but a strong relationship exists between both measures and virus load. However, electronic monitoring is more sensitive than self-report for the detection of nonadherence and should be used in adherence intervention studies.
To study attitudes toward menopause in women with or at risk of human immunodeficiency virus (HIV) aged 35 to 60 in New York City, NY, USA.
Data were obtained at the baseline interview in a cohort study of menopause. Of 502 participating women, 92 were postmenopausal and 162 were perimenopausal.
Overall, 37.5% of women had a relatively favorable attitude toward menopause. African Americans had a 72% greater odds of a positive attitude (OR = 1.72, 95% CI 1.16–2.57) than all other groups after adjusting for covariates. Hispanic women had the least favorable view of menopause. Experience of >3 menopausal symptoms and negative life events—being a witness to a murder, and the death of a child—were significantly associated with negative attitudes towards menopause (OR = 0.62, 95% CI 0.42–0.93 and OR = 0.64, 95% CI 0.43–0.93, respectively). Depressive symptoms, street drug use, and having a domestic partner, which is significant in single variable analyses, did not remain independent predictors in multivariate results. HIV status, menopause status, and age at interview were not associated with menopause attitudes.
HIV-infected, drug-using, low-income women showed generally unfavorable attitudes towards menopause. High stress life events coupled with a high prevalence of depressive symptoms indicate this population has special needs marked by the menopause transition into older age.
menopause; attitudes; HIV; street drug users
Osteopenia has been described in HIV-infected persons, but most studies have not focused on aging men, have not included an HIV-negative comparison group with similar risks to those of the HIV-infected men, or lacked data on fracture rates.
We analyzed bone mineral density (BMD) and incident fractures in 559 men who were ≥ 49 years old with or at-risk for HIV, including 328 with and 231 without HIV infection.
Median age was 55 years, 56% were black and 89% had used illicit drugs. In unadjusted analysis, BMD was lower in HIV-infected compared with HIV-uninfected men at the femoral neck (0.97 ± 0.14 versus 1.00 ± 0.15 g/cm2; P < 0.05) and lumbar spine (1.17 ± 0.20 versus 1.20 ± 0.21 g/cm2; P = 0.06); both differences were significant (P < 0.05) after adjusting for age, weight, race, testosterone level, and prednisone and illicit drug use. Non-black race and body weight were independently associated with BMD at both measurement sites and methadone therapy was independently associated with spine BMD. Among HIV-infected men, 87% had taken antiretrovirals and 74% had taken protease inhibitors, but their use was not associated with BMD. Among men who had at least one subsequent study visit (94%), incident fracture rates per 100 person-years differed among men with normal BMD, osteopenia and osteoporosis (1.4 versus 3.6 versus 6.5; P < 0.01). A 38% increase in fracture rate among HIV-infected men was not statistically significant.
HIV infection is independently associated with modestly reduced BMD in aging men, and decreased BMD is associated with increased fracture risk.
osteopenia; osteoporosis; bone mineral density; bone fractures; antiretroviral therapy; opiate dependence
Increased cardiovascular risk has been linked to HIV infection and combination antiretroviral therapy, but the impact of hepatitis C virus (HCV) status on indices of cardiovascular risk has not been routinely assessed in the HIV-infected population. The objective of this study was to analyze associations of HCV, HIV, and combination antiretroviral therapy with lipid levels and C-reactive protein (CRP) among older men. We measured fasting total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and high-sensitivity CRP serum levels in a cross-sectional study of 108 HIV-infected and 74 HIV-uninfected at-risk older men. One hundred ten men (60%) had detectable HCV RNA, with no difference by HIV status (p = 0.25). The majority (88%) of men with HCV infection had a history of injection drug use. Among all men, HCV infection was independently associated with lower total cholesterol (p < 0.001), LDL-C (p < 0.001), triglycerides (p = 0.01), and CRP (p < 0.001). Among HIV-infected men, HCV infection was associated with lower total cholesterol (p < 0.001), LDL-C (p < 0.001), and CRP (p = 0.004). HCV infection was associated with lower triglycerides among men on protease inhibitors (PI) (p = 0.02) and non-PI combination antiretroviral therapy (p = 0.02), but not among antiretroviral-naïve men. These findings demonstrate an association of lower serum lipid and CRP levels with HCV infection and suggest that HCV status should be assessed as an important correlate of cardiovascular risk factors in studies of older men with or at risk for HIV.
To determine the associations of hepatitis C virus (HCV) infection with insulin resistance and abnormal glucose tolerance in a cohort of older adults with or at risk of HIV infection.
A cross-sectional study of 267 HIV-infected and 179 at-risk-uninfected adults without a history of diabetes mellitus.
HCV antibody assays and RNA levels were performed to assess HCV status. Antiretroviral use, family history of diabetes, sedentary behavior, and sociodemographic data were obtained using standardized interviews. Fasting insulin levels and oral glucose tolerance tests were performed to assess two outcomes, the homeostasis model assessment of insulin resistance and abnormal glucose tolerance [impaired glucose tolerance (IGT) or diabetes].
Of 446 participants, 265 (59%) were HCV seropositive; of these, 199 (75%) had detectable HCV-RNA levels. Insulin resistance was greater among HCV-seropositive compared with seronegative participants, adjusting for body mass index, Hispanic ethnicity, age greater than 55 years, sedentary behavior (watching television > 4 h/day), HIV status, HAART, and protease inhibitor (PI) use. Ninety-eight participants (22%) had abnormal glucose tolerance (69 with IGT and 29 with diabetes). Among HIV-infected participants, 25% were on non-PI HAART and 52% were on PI HAART, but HAART and PI use were not associated with insulin resistance or abnormal glucose tolerance. Among obese participants, abnormal glucose tolerance was more common in HCV-seropositive than seronegative individuals, whereas among non-obese participants there was no association.
The potential impact of HCV co-infection and obesity on glucose metabolism should be recognized in clinical care, and addressed in future research studies of HIV-infected individuals.
Hepatitis C virus; HIV; impaired glucose tolerance; insulin resistance; obesity; type 2 diabetes
Objective. Animal data suggest that cocaine has an immunosuppressive effect, but no human studies have been conducted to assess the relation of cocaine use with human papillomavirus (HPV) infection, the viral cause of cervical cancer. Since both cocaine use and HPV infection are common among HIV-positive women, we sought to determine whether use of cocaine and/or crack influences the natural history of HPV among women with or at high risk of HIV.
Methods. Women enrolled in the Women's Interagency HIV Study (2278 HIV-seropositive and 826 high-risk seronegative women) were examined every six months for up to 9.5 years with Pap smear, collection of cervicovaginal lavage (CVL) samples, and detailed questionnaires regarding health and behavior, including use of crack and cocaine (crack/cocaine). CVLs were tested for HPV DNA by PCR, with genotyping for over forty HPV types.
Results. In multivariate logistic regression models, censoring women treated for cervical neoplasia, crack/cocaine use within the last six months was associated with prevalent detection of oncogenic HPV DNA (odds ratio [OR] = 1.30
(1.09–1.55)), and with oncogenic HPV-positive squamous intraepithelial lesions (SIL) (OR = 1.70 (1.27–2.27)), following adjustment for age, race, HIV-serostatus, and CD4+ T-cell count, the number of sexual partners in the past six months, and smoking. In multivariate Cox models crack/cocaine use was also associated with a trend that approached significance in regard to incident detection of oncogenic HPV-positive SIL (HR = 1.51, 95% CI 0.99–2.30), and while the rate of oncogenic HPV clearance was not related to cocaine use, the clearance of any SIL was significantly lower in those with versus those without recent crack/cocaine use (HR = 0.57, 95% CI 0.34–0.97).
Conclusions. Cocaine use is associated with an increased risk of detection of both prevalent and incident oncogenic HPV infection, as well as an increased risk of HPV-positive SIL over time.
Abnormal glucose metabolism in HIV-infected patients has largely been attributed to protease inhibitor use. However most studies of glucose metabolism in HIV-infected patients have focused on men or have lacked appropriate controls.
We assessed factors associated with previously-diagnosed diabetes among 620 midlife women with- or at-risk for HIV infection. In a subset of 221 women without previously-diagnosed diabetes, we performed an oral glucose tolerance test (OGTT) with insulin levels, and assessed factors associated with abnormal glucose tolerance, insulin resistance, and insulin secretion.
Thirteen percent had previously-diagnosed diabetes. Among women without previously diagnosed diabetes who underwent an OGTT, 6% had undiagnosed diabetes and 12% had impaired glucose tolerance (IGT). On multivariate analysis, factors associated with previously-diagnosed diabetes included current methadone treatment, body mass index, family history of diabetes, and physical inactivity. Factors independently associated with abnormal OGTT (IGT or diabetes) included age ≥50 y, family history of diabetes, physical inactivity, and pack-years of smoking. Factors independently associated with insulin resistance included waist circumference, Hispanic ethnicity, physical inactivity, and among HIV-infected women, use of non-PI HAART. Factors associated with lower insulin secretion included current opiate use (methadone or heroin) and older age.
Abnormal glucose metabolism is highly prevalent among midlife women with or at-risk for HIV infection, particularly those who use opiates. Women with classic diabetes risk factors, rather than solely those taking PIs, should be screened for diabetes in the primary care setting. Interventions targeting modifiable risk factors, including obesity and physical inactivity, are also warranted.
human immunodeficiency virus (HIV); diabetes mellitus; antiretroviral therapy; women; drug use
Selenocysteine incorporation in eukaryotes occurs cotranslationally at UGA codons via the interactions of RNA-protein complexes, one comprised of selenocysteyl (Sec)-tRNA[Ser]Sec and its specific elongation factor, EFsec, and another consisting of the SECIS element and SECIS binding protein, SBP2. Other factors implicated in this pathway include two selenophosphate synthetases, SPS1 and SPS2, ribosomal protein L30, and two factors identified as binding tRNA[Ser]Sec, termed soluble liver antigen/liver protein (SLA/LP) and SECp43. We report that SLA/LP and SPS1 interact in vitro and in vivo and that SECp43 cotransfection increases this interaction and redistributes all three proteins to a predominantly nuclear localization. We further show that SECp43 interacts with the selenocysteyl-tRNA[Ser]Sec-EFsec complex in vitro, and SECp43 coexpression promotes interaction between EFsec and SBP2 in vivo. Additionally, SECp43 increases selenocysteine incorporation and selenoprotein mRNA levels, the latter presumably due to circumvention of nonsense-mediated decay. Thus, SECp43 emerges as a key player in orchestrating the interactions and localization of the other factors involved in selenoprotein biosynthesis. Finally, our studies delineating the multiple, coordinated protein-nucleic acid interactions between SECp43 and the previously described selenoprotein cotranslational factors resulted in a model of selenocysteine biosynthesis and incorporation dependent upon both cytoplasmic and nuclear supramolecular complexes.
Recoding of UGA from a stop codon to selenocysteine poses a dilemma for the protein translation machinery. In eukaryotes, two factors that are crucial to this recoding process are the mRNA binding protein of the Sec insertion sequence, SBP2, and the specialized elongation factor, EFsec. We sought to determine the subcellular localization of these selenoprotein synthesis factors in mammalian cells and thus gain insight into how selenoprotein mRNAs might circumvent nonsense-mediated decay. Intriguingly, both EFsec and SBP2 localization differed depending on the cell line but significant colocalization of the two proteins was observed in cells where SBP2 levels were detectable. We identify functional nuclear localization and export signals in both proteins, demonstrate that SBP2 undergoes nucleocytoplasmic shuttling, and provide evidence that SBP2 levels and localization may influence EFsec localization. Our results suggest a mechanism for the nuclear assembly of the selenocysteine incorporation machinery that could allow selenoprotein mRNAs to circumvent nonsense-mediated decay, thus providing new insights into the mechanism of selenoprotein translation.
To identify gender differences in social and behavioral factors associated with antiretroviral adherence.
Prospective cohort study.
Methadone maintenance program.
One hundred thirteen HIV-seropositive current or former opioid users.
MEASUREMENTS AND MAIN RESULTS
Participants were surveyed at baseline about social and behavioral characteristics and at monthly research visits about drug and alcohol use and medication side effects. Electronic monitors (MEMS) were used to measure antiretroviral adherence. Median adherence among women was 27% lower than among men (46% vs. 73%; P < .05). In gender-stratified multivariate models, factors associated with worse adherence in men included not belonging to an HIV support group (P < .0001), crack/cocaine use (P < .005), and medication side effects (P = .01). Among women, alcohol use (P = .005), heroin use (P < .05), and significant medication side effects (P < .005) were independently associated with worse adherence. In a model including both men and women, worse adherence was associated with lack of long-term housing (P < .005), not belonging to any HIV support groups (P < .0005), crack or cocaine use (P < .01), and medication side effects (P < .0005). In addition, worse adherence was associated with the interaction between female gender and alcohol use (P ≤ .05).
In this cohort of current and former opioid users, gender-stratified analysis demonstrated that different social and behavioral factors are associated with adherence in men and women. Among both men and women, worse adherence was associated with lack of long-term housing, not belonging to an HIV support group, crack/cocaine use, and medication side effects. Among women only, alcohol use was associated with worse adherence.
adherence; gender; alcohol; antiretroviral therapy; electronic monitors
To define the prevalence of and factors associated with having a negative purified protein derivative (PPD) among persons who self-report a prior positive PPD and to define the safety of repeat testing in such persons.
Observational cohort study.
Methadone maintenance program with onsite primary care.
Current or former drug users enrolled in methadone maintenance treatment.
Structured interview, tuberculin skin testing regardless of self-reported PPD status, and anergy testing.
MEASUREMENTS AND MAIN RESULTS
Nearly one third (31%) of participants who self-reported a prior positive PPD had a negative measured PPD, despite receipt of a “booster” PPD. A single participant (0.5%) blistered in response to the PPD without lasting ill effect. Participants with PPD results discordant from their history were more likely to be HIV-seropositive and nonreactive to the anergy panel. The discordance rate among HIV-infected participants was 43%, and was largely attributable to immune dysfunction. Among HIV-seronegative participants, the discordance rate was 27%. Recent crack-cocaine use was independently associated with discordance in the absence of HIV infection.
We confirmed that planting a PPD in patients who self-report a positive PPD history confers minimal risk. Substantial rates of discordance exist between self-reported history of a positive PPD and measured PPD status. Further research is needed to define the optimal management of PPD-negative patients who self-report a prior positive PPD and who have not received prior treatment for latent tuberculosis.
tuberculin skin testing; PPD; tuberculosis screening; drug users
glutathione (GSH) is the most abundant thiol antioxidant in mammalian cells. It directly reacts with reactive oxygen species (ROS), functions as a cofactor of antioxidant enzymes, and maintains thiol redox potential in cells. GSH depletion has been implicated in the pathogenesis of neurological diseases, particularly to Parkinson's disease (PD). The purpose of this study was to investigate the change of cellular antioxidant status and basic cell functions in the relatively early stages of GSH depletion.
in this study, GSH was depleted by inhibition of glutamylcysteine synthetase using buthionine sulfoximine (BSO) treatment in Ht22, a neuronal cell line derived from mouse hippocampus. Treatment with BSO produced dose-dependent decreases in total GSH level, Fe3+-reducing ability (FRAP assay), Cu2+-reducing ability (Antioxidant Potential, AOP assay), and ABTS free radical scavenging ability (ABTS assay) of the cells, but the sensitivity of these indicators to dosage varied considerably. Most of the changes were completed during the first 8 hours of treatment. Cell viability was tested by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromid) assay, and cells at lower density in culture were found to be more sensitive to GSH depletion. The activity of antioxidant enzymes, such as glutathione peroxidase (GPx), glutathione reductase (GR), and copper/zinc superoxide dismutase (Cu/Zn-SOD) were affected by GSH depletion. A cDNA expression array assay of the effects of BSO treatment showed significantly decreased mRNA level for 3 genes, and significantly increased mRNA level for 10 genes, including the antioxidant enzymes Cu/Zn-SOD and thioredoxin peroxidase 2 (TPxII).
the study suggests that there are BSO-sensitive and BSO-resistant pools of GSH in Ht22 cells, and that different categories of antioxidant react differently to GSH depletion. Further, the effect of GSH status on cell viability is cell density dependent. Finally, the alterations in expression or activity of several antioxidant enzymes provide insight into the various cellular responses to GSH depletion.
Despite a burgeoning literature on adherence to HIV therapies, few studies have examined the impact of ongoing drug use on adherence and viral suppression, and none of these have utilized electronic monitors to quantify adherence among drug users. We used 262 electronic monitors to measure adherence with all antiretrovirals in 85 HIV-infected current and former drug users, and found that active cocaine use, female gender, not receiving Social Security benefits, not being married, screening positive for depression, and the tendency to use alcohol or drugs to cope with stress were all significantly associated with poor adherence. The strongest predictor of poor adherence and, in turn, failure to maintain viral suppression, was active cocaine use. Overall adherence among active cocaine users was 27%, compared to 68% among subjects who reported no cocaine use during the 6-month study period. Consequently, 13% of active cocaine users maintained viral suppression, compared to 46% of nonusers. Interventions to improve adherence should focus on reducing cocaine use, developing adaptive coping skills, and identifying and treating depression.
adherence; drug users; antiretroviral therapy; electronic monitors
The DR-70® (FDP) test was the first cancer test cleared by USFDA for monitoring colorectal cancer (CRC) since Carcinoembryonic Antigen (CEA) in 1982. Conservatively, 50% of biopsy-positive CRC patients have negative CEA values. DR-70 and CEA values were compared for 113 CRC monitoring patients. Total concordance rates for DR-70 and CEA were 0.665 and 0.686, respectively. CRC patient pairs were grouped based on their CEA value to deduce DR-70's effectiveness at monitoring patients with low CEA values. DR-70 had 12% to 100% greater positive concordance rates than CEA in this group. DR-70 is a welcome new option for CRC patients.
carcinoembryonic antigen; CEA; colorectal cancer; DR-70®; FDP; fibrinfibrinogen degradation products