HIV-infected patients with substance use experience suboptimal health outcomes, possibly to due to variations in care.
To assess the association between substance use and the quality of HIV care (QOC) received.
Retrospective cohort study.
HIV-infected patients enrolled in the Veterans Aging Cohort Study.
We collected self-report substance use data and abstracted 9 HIV quality indicators (QIs) from medical records. Independent variables were unhealthy alcohol use (AUDIT-C score ≥4) and illicit drug use (self-report of stimulants, opioids, or injection drug use in past year). Main outcome was the percentage of QIs received, if eligible. We estimated associations between substance use and QOC using multivariable linear regression.
The majority of the 3,410 patients were male (97.4%) and Black (67.0%) with a mean age of 49.1 years (SD 8.8). Overall, 25.8% reported unhealthy alcohol use, 22% illicit drug use, and participants received 81.5% (SD=18.9) of QIs. The mean percentage of QIs received was lower for those with unhealthy alcohol use vs. not (59.3% vs. 70.0%, p<.001) and those using illicit drugs vs. not (57.8% vs. 70.7%, p<.001). In multivariable models, unhealthy alcohol use (adjusted β −2.74; 95% CI −4.23, −1.25) and illicit drug use (adjusted β −3.51 95% CI −4.99, −2.02) remained inversely associated with the percentage of QIs received.
Though the overall QOC for these HIV-infected Veteran patients was high, gaps persist for those with unhealthy alcohol and illicit drug use. Interventions that address substance use in HIV-infected patients may improve the QOC received.
Alcohol; Quality of Health Care; HIV; Quality Indicators; Health Care; Opioid-Related Disorders
We investigated the association between human immunodeficiency virus (HIV) and prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation in a cohort of HIV-infected and uninfected veterans who had a comparable burden of comorbid conditions.
Background. Biomarkers of inflammation, altered coagulation, and monocyte activation are associated with mortality and cardiovascular disease (CVD) in the general population and among human immunodeficiency virus (HIV)–infected people. We compared biomarkers for inflammation, altered coagulation, and monocyte activation between HIV-infected and uninfected people in the Veterans Aging Cohort Study (VACS).
Methods. Biomarkers of inflammation (interleukin-6 [IL-6]), altered coagulation (d-dimer), and monocyte activation (soluble CD14 [sCD14]) were measured in blood samples from 1525 HIV-infected and 843 uninfected VACS participants. Logistic regression was used to determine the association between HIV infection and prevalence of elevated (>75th percentile) biomarkers, adjusting for confounding comorbidities.
Results. HIV-infected veterans had less prevalent CVD, hypertension, diabetes, obesity, hazardous drinking, and renal disease, but more dyslipidemia, hepatitis C, and current smoking than uninfected veterans. Compared to uninfected veterans, HIV-infected veterans with HIV-1 RNA ≥500 copies/mL or CD4 count <200 cells/µL had a significantly higher prevalence of elevated IL-6 (odds ratio [OR], 1.54; 95% confidence interval [CI],1.14–2.09; OR, 2.25; 95% CI, 1.60–3.16, respectively) and d-dimer (OR, 1.97; 95% CI, 1.44–2.71, OR, 1.68; 95% CI, 1.22–2.32, respectively) after adjusting for comorbidities. HIV-infected veterans with a CD4 cell count <200 cells/µL had significantly higher prevalence of elevated sCD14 compared to uninfected veterans (OR, 2.60; 95% CI, 1.64–4.14). These associations still persisted after restricting the analysis to veterans without known confounding comorbid conditions.
Conclusions. These data suggest that ongoing HIV replication and immune depletion significantly contribute to increased prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation. This contribution is independent of and in addition to the substantial contribution from comorbid conditions.
We describe the transfer of blaKPC-4 from Enterobacter cloacae to Serratia marcescens in a single patient. DNA sequencing revealed that KPC-4 was encoded on an IncL/M plasmid, pNE1280, closely related to pCTX-M360. Further analysis found that KPC-4 was encoded within a novel Tn4401 element (Tn4401f) containing a truncated tnpA and lacking tnpR, ISKpn7 left, and Tn4401 IRL-1, which are conserved in other Tn4401 transposons. This study highlights the continued evolution of Tn4401 transposons and movement to multiple plasmid backbones that results in acquisition by multiple species of Gram-negative bacilli.
Epidemics of both HIV/AIDS and alcohol abuse in sub-Saharan Africa have spurred the conduct of local behavioral therapy trials for these problems, but the ethical issues involved in these trials have not been fully examined. In this paper, we discuss ethical issues that emerged during the conduct of a behavioral intervention adaptation and trial using cognitive-behavioral therapy to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya. The study was performed within our multinational collaboration, the USAID-Academic Model Providing Access to Healthcare Partnership. We discuss relevant ethical considerations and how we addressed them.
HIV; AIDS; alcohol abuse; cognitive behavioral therapy; ethical issues; sub-Saharan Africa
Patterns of comorbidity among persons with human immunodeficiency virus (HIV) are not well described. We compared comorbidity among veterans with and without HIV infection. The sample consisted of 33,420 HIV-infected veterans and 66,840 HIV-uninfected veterans. We identified and clustered 11 comorbid conditions using validated International Classification of Diseases, 9th Revision, Clinical Modification codes. We defined multimorbidity as the presence of conditions in all clusters. Models restricted to HIV-infected veterans were adjusted for CD4 cell count and viral load. Comorbidity was common (prevalence, 60%–63%), and prevalence varied by HIV status. Differences remained when the veterans were stratified by age. In multivariable analyses, older HIV-infected veterans were more likely to have substance use disorder and multimorbidity. Renal, vascular, and pulmonary diseases were associated with CD4 cell count <200 cells/mm3; hypertension was associated with CD4 cell count >200 cells/mm3. Comorbidity is the rule, and multimorbidity is common among veterans with HIV infection. Patterns of comorbidity differ substantially by HIV status, age, and HIV severity. Primary care guidelines require adaptation for persons with HIV infection.
The Veterans Aging Cohort Study (VACS) Index, based on age and 8 routine clinical tests, is strongly correlated with 3 biomarkers of inflammation: interleukin 6 (IL-6), D-dimer, and soluble CD14 (sCD14). After adjustment for the VACS Index, D-dimer and sCD14, but not IL-6, remain independently associated with mortality.
Background. When added to age, CD4 count and human immunodeficiency virus type 1 (HIV-1) RNA alone (Restricted Index), hemoglobin, FIB-4 Index, hepatitis C virus (HCV), and estimated glomerular filtration rate improve prediction of mortality. Weighted and combined, these 7 routine clinical variables constitute the Veterans Aging Cohort Study (VACS) Index. Because nonroutine biomarkers of inflammation (interleukin 6 [IL-6]), coagulation (D-dimer), and monocyte activation (sCD14) also predict mortality, we test the association of these indices and biomarkers with each other and with mortality.
Methods. Samples from 1302 HIV-infected veterans on antiretroviral therapy were analyzed. Indices were calculated closest to date of collection. We calculated Spearman correlations stratified by HIV-1 RNA and HCV status and measured association with mortality using C statistics and net reclassification improvement (NRI).
Results. Of 1302 subjects, 915 had HIV-1 RNA <500 copies/mL and 154 died. The VACS Index was more correlated with IL-6, D-dimer, and sCD14 than the Restricted Index (P < .001). It was also more predictive of mortality (C statistic, 0.76; 95% confidence interval [CI], .72–.80) than any biomarker (C statistic, 0.66–0.70) or the Restricted Index (C statistic, 0.71; 95% CI, .67–.75). Compared to the Restricted Index alone, NRI resulted from incremental addition of VACS Index components (10%), D-dimer (7%), and sCD14 (4%), but not from IL-6 (0%).
Conclusions. Among HIV-infected individuals, independent of CD4, HIV-1 RNA, and age, hemoglobin and markers of liver and renal injury are associated with inflammation. Addition of D-dimer and sCD14, but not IL-6, improves the predictive accuracy of the VACS Index for mortality.
We sought to determine the impact of naltrexone on hepatic enzymes and HIV biomarkers in HIV-infected patients.
We used data from the Veterans Aging Cohort Study-Virtual Cohort, an electronic database of administrative, pharmacy and laboratory data. We restricted our sample to HIV-infected patients who received an initial oral naltrexone prescription, of at least seven days duration. We examined aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and HIV biomarker (CD4 and HIV RNA) values for the 365 days prior to, during, and for the 365 days post-naltrexone prescription. We also examined cases of liver enzyme elevation (LEE; defined as greater than 5 times baseline ALT or AST or greater than 3.5 times baseline if baseline ALT or AST was greater than or equal to 40 IU/L).
Of 114 HIV-infected individuals, 97% were male, 65% white, 57% Hepatitis C co-infected, median age was 49 years; 89% of the sample had a history of alcohol dependence and 32% had opioid dependence. Median duration of naltrexone prescription was 49 (interquartile range 30–83) days, representing 9,525 person-days of naltrexone use. Mean ALT and AST levels remained below the upper limit of normal. Two cases of LEE occurred. Mean CD4 count remained stable and mean HIV RNA decreased after naltrexone prescription.
In HIV-infected patients, oral naltrexone is rarely associated with clinically significant ALT or AST changes and does not have a negative impact on biologic parameters. Therefore, HIV-infected patients with alcohol or opioid dependence can be treated with naltrexone.
Dual epidemics of HIV and alcohol use disorders, and a dearth of professional resources for behavioral treatment in sub-Saharan Africa, suggest the need for development of culturally relevant and feasible interventions. The purpose of this study was to test the preliminary efficacy of a culturally adapted 6-session gender-stratified group cognitive-behavioral therapy (CBT) intervention delivered by paraprofessionals to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya.
Randomized clinical trial comparing CBT against a usual care assessment only control
A large HIV outpatient clinic in Eldoret, Kenya, part of the Academic Model for Providing Access to Healthcare collaboration
75 HIV-infected outpatients who were antiretroviral (ARV)-initiated or ARV-eligible and who reported hazardous or binge drinking
Percent drinking days (PDD) and mean drinks per drinking days (DDD) measured continuously using the Timeline Followback
There were 299 ineligible and 102 eligible outpatients with 12 refusals. Effect sizes of the change in alcohol use since baseline between the two conditions at the 30-day follow-up were large (d=.95, p=.0002, mean difference=24.93 (95% CI: 12.43, 37.43) PDD; d=.76, p=.002, mean difference=2.88 (95% CI: 1.05, 4.70) DDD). Randomized participants attended 93% of the 6 CBT sessions offered. Reported alcohol abstinence at the 90-day follow-up was 69.4% (CBT) and 37.5% (usual care). Paraprofessional counselors achieved independent ratings of adherence and competence equivalent to college-educated therapists in the U.S. Treatment effect sizes were comparable to alcohol intervention studies conducted in the U.S.
Cognitive-behavioral therapy can be successfully adapted to group paraprofessional delivery in Kenya and may be effective in reducing alcohol use among HIV-infected Kenyan outpatients.
BACKGROUND AND OBJECTIVE
Food insecurity negatively impacts HIV disease outcomes in international settings. No large scale U.S. studies have investigated the association between food insecurity and severity of HIV disease or the mechanism of this possible association. The objective of this study was to examine the impact of food insecurity on HIV disease outcomes in a large cohort of HIV-infected patients receiving antiretroviral medications.
This is a cross-sectional study.
PARTICIPANTS AND SETTING
Participants were HIV-infected patients enrolled in the Veterans Aging Cohort Study between 2002–2008 who were receiving antiretroviral medications.
Participants reporting “concern about having enough food for you or your family in the past 30 days” were defined as food insecure. Using multivariable logistic regression, we explored the association between food insecurity and both low CD4 counts (<200 cells/μL) and unsuppressed HIV-1 RNA (>500 copies/mL). We then performed mediation analysis to examine whether antiretroviral adherence or body mass index mediates the observed associations.
Among 2353 HIV-infected participants receiving antiretroviral medications, 24% reported food insecurity. In adjusted analyses, food insecure participants were more likely to have an unsuppressed HIV-1 RNA (AOR 1.37, 95% CI 1.09, 1.73) compared to food secure participants. Mediation analysis revealed that neither antiretroviral medication adherence nor body mass index contributes to the association between food insecurity and unsuppressed HIV-1 RNA. Food insecurity was not independently associated with low CD4 counts.
Among HIV-infected participants receiving antiretroviral medications, food insecurity is associated with unsuppressed viral load and may render treatment less effective. Longitudinal studies are needed to test the potential causal association between food insecurity, lack of virologic suppression, and additional HIV outcomes.
food insecurity; HIV; patients; antiretrovirals
Whether hepatitis C (HCV) confers additional coronary heart disease (CHD) risk among Human Immunodeficiency Virus (HIV) infected individuals is unclear. Without appropriate adjustment for antiretroviral therapy, CD4 count, and HIV-1 RNA, and substantially different mortality rates among those with and without HIV and HCV infection, the association between HIV, HCV, and CHD may be obscured.
Methods and Results
We analyzed data on 8579 participants (28% HIV+, 9% HIV+HCV+) from the Veterans Aging Cohort Study Virtual Cohort who participated in the 1999 Large Health Study of Veteran Enrollees. We analyzed data collected on HIV and HCV status, risk factors for and the incidence of CHD, and mortality from 1/2000–7/2007. We compared models to assess CHD risk when death was treated as a censoring event and as a competing risk. During the median 7.3 years of follow-up, there were 194 CHD events and 1186 deaths. Compared with HIV−HCV− Veterans, HIV+ HCV+ Veterans had a significantly higher risk of CHD regardless of whether death was adjusted for as a censoring event (adjusted hazard ratio (HR)=2.03, 95% CI=1.28–3.21) or a competing risk (adjusted HR=2.45, 95% CI=1.83–3.27 respectively). Compared with HIV+HCV− Veterans, HIV+ HCV+ Veterans also had a significantly higher adjusted risk of CHD regardless of whether death was treated as a censored event (adjusted HR=1.93, 95% CI=1.02–3.62) or a competing risk (adjusted HR =1.46, 95% CI=1.03–2.07).
HIV+HCV+ Veterans have an increased risk of CHD compared to HIV+HCV−, and HIV−HCV− Veterans.
viruses; coronary disease; mortality; multi morbidity
Traditional homemade brew is believed to represent the highest proportion of alcohol use in sub-Saharan Africa. In Eldoret, Kenya, two types of brew are common: chang’aa, spirits, and busaa, maize beer. Local residents refer to the amount of brew consumed by the amount of money spent, suggesting a culturally relevant estimation method. The purposes of this study were to analyze ethanol content of chang’aa and busaa; and to compare two methods of alcohol estimation: use by cost, and use by volume, the latter the current international standard. Laboratory results showed mean ethanol content was 34% (SD = 14%) for chang’aa and 4% (SD = 1%) for busaa. Standard drink unit equivalents for chang’aa and busaa, respectively, were 2 and 1.3 (US) and 3.5 and 2.3 (Great Britain). Using a computational approach, both methods demonstrated comparable results. We conclude that cost estimation of alcohol content is more culturally relevant and does not differ in accuracy from the international standard.
Alcohol; Traditional brew; HIV; Kenya; Cognitive behavioral treatment
This study characterized the extent and patterns self-reported drug use among aging adults with and without HIV, assessed differences in patterns by HIV status, and examined pattern correlates. Data derived from 6351 HIV infected and uninfected adults enrolled in an eight-site matched cohort, the Veterans Aging Cohort Study (VACS). Using clinical variables from electronic medical records and sociodemographics, drug use consequences, and frequency of drug use from baseline surveys, we performed latent class analyses (LCA) stratified by HIV status and adjusted for clinical and socio-demographic covariates. Participants were, on average, age 50 (range 22–86), primarily male (95%) and African-American (64%). Five distinct patterns emerged: non-users, past primarily marijuana users, past multidrug users, current high consequence multidrug users, and current low consequence primarily marijuana users. HIV status strongly influenced class membership. Non -users were most p revalent among HIV uninfected (36.4%) and current high consequence multidrug users (25.5%) were most prevalent among HIV infected. While problems of obesity marked those not currently u sing drugs, current users experienced higher prevalences of medical or mental health disorders. Multimorbidity was highest among past and current multidrug users. HIV-infected participants were more likely than HIV-uninfected participants to be current low consequence primarily marijuana users. In this sample, active drug use and abuse were common. HIV infected and uninfected Veterans differed on extent and patterns of drug use and on important characteristics within identified classes. Findings have the potential to inform screening and intervention efforts in aging drug users with and without HIV.
aging; Veterans; HIV; substance-related disorders; latent class analysis; illicit drugs; cohort studies
Depression is one of the most common comorbid conditions affecting persons with HIV. We compared depressive symptoms and depression treatment using data from the Veterans Aging Cohort Study (VACS), a prospective cohort of HIV-infected and uninfected subjects. We identified subjects with a Patient Health Questionnaire score of 10 or greater. Treatment was defined as prescription of a selective serotonin reuptake inhibitor (SSRI) or mental health counseling. Overall, 16% of 4,480 subjects had depressive symptoms, and HIV-infected patients were more likely to have had depressive symptoms (OR = 1.38, 95% CI = 1.18, 1.62). Geographic site of care and having a mental health provider at the clinic was associated with treatment. In multivariable models restricted to 732 patients with depressive symptoms, receipt of depression treatment did not differ by HIV status (Adjusted OR = 1.11, 95% CI = 0.80, 1.54). Non-Hispanic whites were more likely to receive treatment (Adjusted OR = 2.09, 95% CI 1.04, 4.24). Primary care and HIV providers were equally unlikely to treat active depressive symptoms. Treatment variation by race, site, and availability of a mental health provider, suggests targets for intervention.
HIV-infection; Depression; Psychiatric status rating scales; Anti-depressive agents
Screening for hazardous drinking may fail to detect a substantial proportion of individuals harmed by alcohol. We investigated whether considering an individual’s usual drinking quantity or threshold for alcohol-induced cognitive impairment improves the prediction of nonadherence with prescribed medications.
Cross-sectional analysis of participants in a large, multi-site cohort study. We used the timeline followback to reconstruct 30-day retrospective drinking histories and the timeline followback modified for adherence to reconstruct 30-day medication adherence histories among 3,152 individuals in the Veterans Aging Cohort Study, 1,529 HIV infected and 1,623 uninfected controls. We categorized daily alcohol consumption by using quantity alone, quantity after adjustment for the individual’s mean daily alcohol consumption, and self-reported level of impairment corresponding to each quantity. A standard drink was defined as 14 g of ethanol. Nonadherence was defined as the proportion of days with ≥1 medication doses missed or taken ≥2 hours late, and clinically significant nonadherence was defined as ≥5% absolute increase in the proportion of days with nonadherence.
The mean adjusted- and impairment-based methods showed greater discrimination of nonadherence risk compared to the measure based on quantity alone (quantity-based categorization, 3.2-fold increase; quantity adjusted for mean daily consumption, 4.6-fold increase, impairment-based categorization, 3.6-fold increase). The individualized methods also detected greater numbers of days with clinically significant nonadherence associated with alcohol. Alcohol was associated with clinically significant nonadherence at a lower threshold for HIV infected versus uninfected patients (2 standard drinks vs. 4 standard drinks) using quantity-based categorization, but this difference was no longer apparent when individualized methods were used.
Tailoring screening questions to an individual’s usual level of alcohol consumption or threshold for impairment improves the ability to predict alcohol-associated medication nonadherence.
Human Immunodeficiency Virus; Alcohol; Nonadherence
Two-thirds of those with HIV worldwide live in sub-Saharan Africa. Alcohol use is associated with the HIV epidemic through risky sex and suboptimal ARV adherence. In western Kenya, hazardous drinking was reported by HIV (53%) and general medicine (68%) outpatients. Cognitive behavioral treatment (CBT) has demonstrated strong efficacy to reduce alcohol use. This article reports on a systematic cultural adaptation and pilot feasibility study of group paraprofessional-delivered CBT to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya. Following adaptation and counselor training, five pilot groups were run (n=27). Overall attendance was 77%. Percent days abstinent from alcohol (PDA) before session 1 was 52%–100% (women) and 21–36% (men), and by session 6 was 96%–100% (women) and 89%–100% (men). PDA effect sizes (Cohen’s d) between first and last CBT session were 2.32 (women) and 2.64 (men). Participants reported treatment satisfaction. Results indicate feasibility, acceptability and preliminary efficacy for CBT in Kenya.
alcohol; cognitive behavioral therapy; cultural adaptation; HIV; Kenya
The Veterans Aging Cohort Study (VACS) is a study of human immunodeficiency virus (HIV) infected and uninfected patients seen in infectious disease and general medical clinics. VACS includes the earlier 3 and 5 site studies (VACS 3 and VACS 5) as well as the ongoing 8 site study.
We sought to provide background and context for analyses based upon VACS data, including study design and rationale as well as its basic protocol and the baseline characteristics of the enrolled sample.
We undertook a prospectively consented multisite observational study of veterans in care with and without HIV infection.
Data were derived from patient and provider self report, telephone interviews, blood and DNA samples, focus groups, and full access to the national VA “paperless” electronic medical record system.
More than 7200 veterans have been enrolled in at least one of the studies. The 8 site study (VACS) has enrolled 2979 HIV-infected and 3019 HIV-uninfected age–race–site matched comparators and has achieved stratified enrollment targets for race/ethnicity and age and 99% of its total target enrollment as of October 30, 2005. Participants in VACS are similar to other veterans receiving care within the VA. VACS participants are older and more predominantly black than those reported by the Centers for Disease Control.
VACS has assembled a rich, in-depth, and representative sample of veterans in care with and without HIV infection to conduct longitudinal analyses of questions concerning the association between alcohol use and related comorbid and AIDS-defining conditions.
HIV/AIDS; alcohol; aging veterans; data management/research design
The purpose of this study was to validate the use of Leigh’s (1990) alcohol sex expectancies scale among HIV-infected individuals presenting for treatment as a way to facilitate research on sexual risk reduction among individuals in that population. The participants were 944 men who presented for treatment at infectious disease or general medicine clinics across 8 different VA Medical Center sites. A total of 534 of these men were HIV-positive and 410 were HIV-negative. The total sample was randomly divided in half within each HIV group to form exploratory (Sample 1) and confirmatory (Sample 2) subsamples. A principal components factor analysis with oblique rotation of the original 13-item Leigh scale within each HIV group in Sample 1 revealed a 2-factor (7 and 4 items, respectively) solution that was consistent across both HIV groups. These factors were named “More Open to Sexual Pleasure” (Factor 1) and “Reduced Inhibitions about Sex (Factor 2).” A confirmatory factor analysis of the 11-item, 2-factor solution on the full Sample 2 showed a modest fit to the data, excellent internal consistency reliability of both factors, a high correlation between the factors, and strong evidence for construct validity. These results were interpreted as supporting the use of the 11-item, 2-factor version of Leigh’s scale in studies of clinical samples of HIV-positive adults, and directions for research on further scale refinement are discussed.
Leigh (1990) scale; Alcohol sex expectancies; HIV-positive; Validation
Uncertainty about the value of antiretroviral therapy (ARV) adherence interventions may be a barrier to implementation and evaluation. Our objective is to estimate the minimum effectiveness required for ARV adherence interventions to deliver acceptable value.
We used a validated HIV computer simulation to estimate the impact of ARV adherence interventions on incremental costs and life expectancy. Across a wide range of intervention costs ($1000–10,000, one time or per year), we estimated the smallest effect size compatible with acceptable value (incremental cost-effective ratio ≤$100,000 per life-year), Effect sizes were measured using relative risk (RR) and absolute risk reduction (ARR), and these metrics were applied to nonadherence and nonadherence risk factors. Costs were estimated from a societal perspective ($2003) discounted at 3%.
To give acceptable value, a one-time $1000 intervention must reduce ARV nonadherence by RR ≤ 0.82 (ARR ≥ 0.04) for moderately nonadherent patients (20% of ARV doses missed) and RR ≤ 0.90 (ARR ≥ 0.05) for severely nonadherent patients (50% of ARV doses missed). A one-time $5000 intervention has an unacceptable value regardless of effect size for moderately nonadherent patients, and must reduce ARV nonadherence by RR ≤ 0.31 (ARR ≥ 0.69) for severely nonadherent patients. Interventions aimed at behavioral risk factors (e.g.. unhealthy alcohol use) may confer acceptable value (e.g., if ≤$2000 and effect RR ≤ 0.71 [ARR ≥ 0.29]).
ARV adherence interventions with plausible effect sizes may offer favorable value it they cost <$5000 one time or per year. ARV adherence interventions with a favorable value should become more integral components of HIV care.
adherence; AIDS; cost-effectiveness analysis; health services
To determine whether alcohol consumption is associated with cardiovascular disease (CVD) among HIV infected veterans
Using established thresholds for alcohol consumption, we analyzed cross-sectional data from 4743 men 51% HIV infected) from the Veterans Aging Cohort Study, a prospective cohort of HIV infected and demographically similar uninfected veterans. Using logistic regression, we estimated the odds ratio (OR) for the association between alcohol consumption and prevalent CVD.
Among HIV infected and uninfected men respectively, hazardous drinking (33.2% vs. 30.9%,), alcohol abuse and dependence (20.9% vs. 26.2%), and CVD (14.6% vs. 19.8%) were common. Among HIV infected men, hazardous drinking (OR=1.43, 95% confidence interval (CI)=1.05-1.94) and alcohol abuse and dependence (OR=1.55, 95% CI=1.07-2.23) were associated with a higher prevalence of CVD compared with infrequent and moderate drinking. Among HIV uninfected men, past drinkers had a higher prevalence of CVD (OR=1.30, 95% CI=1.01-1.67). For HIV infected and uninfected men, traditional risk factors and kidney disease were associated with CVD.
Among HIV infected men, hazardous drinking and alcohol abuse and dependence were associated with a higher prevalence of CVD compared with infrequent and moderate drinking even after adjusting for traditional CVD risk factors, antiretroviral therapy, and CD 4 count.
alcohol consumption; alcohol abuse; alcohol dependence; HIV infection; cardiovascular disease; Veterans
The highly conserved macromolecular synthesis operon (MMSO) contains both dnaG (primase) and sigA (primary sigma factor). However, in previously evaluated gram-positive species, the MMSO is divergent upstream of dnaG. The MMSO of Bacillus subtilis contains three open reading frames (ORFs) that are differentially regulated by multiple promoters. In conjunction with studies to determine the expression profile of dnaG, the MMSO of Staphylococus epidermidis was characterized.
The ORFs of S. epidermidis were compared to the previously described MMSO of B. subtilis and two additional ORFs in S. epidermidis, serp1129 and serp1130, were identified. The largest transcript, 4.8 kb in length, was expressed only in exponential growth and encompassed all four ORFs (serp1130, serp1129, dnaG, and sigA). A separate transcript (1.5 kb) comprising serp1130 and serp1129 was expressed in early exponential growth. Two smaller transcripts 1.3 and 1.2 kb in size were detected with a sigA probe in both exponential and post-exponential phases of growth. Western blot analysis correlated with the transcriptional profile and demonstrated that Serp1129 was detected only in the exponential phase of growth. Computational analysis identified that Serp1130 contained a CBS motif whereas Serp1129 contained an ATP/GTP binding motif. Functional studies of Serp1129 demonstrated that it was capable of binding both ATP and GTP. Comparisons with a sigB:dhfr mutant revealed that the 1.3 kb sigA transcript was regulated by a σB-dependent promoter.
These studies demonstrated that the S. epidermidis 1457 MMSO contains two ORFs (serp1129 and serp1130) not described within the B. subtilis MMSO and at least three promoters, one of which is σβ-dependent. The transcriptional regulation of sigA by σB provides evidence that the staphylococcal σB-dependent response is controlled at both the transcriptional and post-transcriptional level. The conservation of serp1129 across multiple gram-positive organisms and its capability to bind ATP and GTP support the need for further investigation of its role in bacterial growth.
Antiretroviral therapy (ART) has substantially altered the fate of HIV-infected people, transforming the infection from an invariably fatal disease to a chronic condition manageable by pharmacotherapy. However, in order for ART to be effective, patients must adhere strictly to an often-demanding treatment regimen. Alcohol consumption may impact survival of HIV-infected patients through a variety of pathways. Some of these are not related to the effectiveness of ART (e.g., alcohol-induced immunosuppression that exacerbates the HIV-related immunosuppression, increased hepatotoxicity, and increased mortality from non–HIV-related causes). However, some pathways mediating alcohol’s negative effect on survival are related to ART effectiveness. In particular, alcohol consumption may reduce adherence to ART, leading to decreased ART effectiveness and, ultimately, increased HIV-related mortality. Both clinical data and computer simulations have yielded information about the impact of alcohol consumption on medication adherence in both HIV-infected and noninfected patients. The findings suggest that alcohol-related nonadherence may account for a substantial amount of preventable mortality among HIV-infected patients. These findings may have clinical implications with respect to optimal treatment for HIV-infected patients who also consume alcohol.
Alcohol consumption; human immunodeficiency virus (HIV); HIV treatment; antiretroviral therapy; medication adherence; immunosuppression
Many people at risk for or already infected with HIV abuse alcohol, contributing to the difficulties in preventing the spread of the infection and treating infected patients. Thus, alcohol-abusing patients may delay testing for HIV, accessing appropriate medical care, and initiating antiretroviral therapy (ART), which may hasten disease progression to full-blown AIDS. Alcohol abuse also increases the risk of HIV infection by promoting risky behaviors and counteracting efforts to minimize the risk of infection, prevent transmission of the virus to others once exposure has occurred, and reduce the risk of progression and organ or tissue injury after infection. In HIV-infected people undergoing treatment, concurrent alcohol abuse often renders treatment ineffective because patients frequently fail to adhere to the strict treatment regimens necessary to achieve control of the infection. Moreover, alcohol may interact with ART medications and exacerbate adverse effects of these medications. Future research needs to better integrate behavioral and biological research to identify strategies to prevent the spread of HIV infection in alcohol-abusing populations as well as focus on translational research to effectively implement promising approaches on a large scale.
Alcohol consumption; alcohol abuse; alcohol and other drug effects and consequences; risk factors; risky sexual behavior; human immunodeficiency virus; acquired immune deficiency syndrome
HIV remains a major cause of preventable morbidity and mortality in Kenya. The effects of behaviors that accompany unhealthy alcohol consumption are a pervasive risk factor for HIV transmission and progression. Our objective was to estimate the portion of HIV infections attributable to unhealthy alcohol use and to evaluate the impact of hypothetical interventions directed at unhealthy alcohol use on HIV infections and deaths.
We estimated outcomes over a time horizon of 20 years using a computer simulation of the Kenyan population. This computer simulation integrates a compartmental model of HIV transmission with a mechanistic model of HIV progression that was previously validated in sub-Saharan Africa. Integration of the transmission and progression models allows simultaneous consideration of alcohol's effects on HIV transmission and progression (e.g., lowering antiretroviral adherence may increase transmission risk by elevating viral load, and may simultaneously increase progression by increasing the likelihood of AIDS). The simulation considers important aspects of heterogeneous sexual mixing patterns, including assortativeness of partners by age and activity level, age-discordant relationships, and high activity subgroups. Outcomes included number of new HIV infections, number of AIDS deaths, and infectivity (number of new infections per infected person per year).
Our model estimated that the effects of behaviors accompanying unhealthy alcohol consumption are responsible for 13.0% of new HIV infections in Kenya. An alcohol intervention with effectiveness similar to that observed in a published randomized controlled trial of a cognitive-behavioral therapy-based intervention in Kenya (45% reduction in unhealthy alcohol consumption) could prevent nearly half of these infections, reducing their number by 69,858 and reducing AIDS deaths by 17,824 over 20 years. Estimates were sensitive to assumptions with respect to the magnitude of alcohol's underlying effects on condom use, antiretroviral therapy adherence, and sexually transmitted infection prevalence.
A substantial number of new HIV infections in Kenya are attributable to unhealthy alcohol use. An alcohol intervention with the effectiveness observed in a published randomized controlled trial has the potential to reduce infections over 20 years by nearly 5% and avert nearly 18,000 deaths related to HIV.
Unhealthy Alcohol Use; HIV Prevention; HIV/AIDS; Sub-Saharan Africa