Howard Libman

Primary Care Guidelines for the Management of Persons Infected with Human Immunodeficiency Virus: 2009 Update by the HIV Medicine Association of the Infectious Diseases Society of America

Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America. These updated guidelines replace those published in 2004. The guidelines are intended for use by health care providers who care for HIV-infected patients or patients who may be at risk for acquiring HIV infection. Since 2004, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve. However, with fewer complications and increased survival, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself and its treatment. HIV-infected persons should be managed and monitored for all relevant age- and gender-specific health problems. New information based on publications from the period 2003-2008 has been incorporated into this document.

Alcohol Consumption and HIV Disease Progression

Objective:To assess the relation between alcohol consumption and laboratory markers of HIV disease progression. Methods:We prospectively assessed CD4 cell counts, HIV RNA levels, and alcohol consumption for up to 7 years in 595 HIV-infected persons with alcohol problems recruited between 1997 and 2003. We investigated the relation of these markers of HIV disease progression to alcohol consumption using longitudinal regression models controlling for known prognostic factors, including adherence and depressive symptoms, and stratified by antiretroviral therapy (ART) use. Results:Among subjects who were not on ART, heavy alcohol consumption was associated with a lower CD4 cell count (adjusted mean decrease of 48.6 cells/μL compared with abstinence; P = 0.03) but not with higher log10 HIV RNA. Among subjects who were on ART, heavy alcohol consumption was not associated with a lower CD4 cell count or higher log10 HIV RNA. Conclusions:Heavy alcohol consumption has a negative impact on the CD4 cell count in HIV-infected persons not receiving ART. In addition to the known deleterious effects of alcohol on ART adherence, these findings suggest that avoiding heavy alcohol consumption in patients not on ART may have a beneficial effect on HIV disease progression.

Delays in protease inhibitor use in clinical practice

AbstractOBJECTIVE: To determine the clinical factors associated with delayed protease inhibitor initiation. DESIGN: Chart review and telephone survey. SETTING: General medicine practice at an academic medical center in Boston, Mass. PATIENTS: One hundred ninety patients living with HIV and a viral load of more than 10,000 copies/ml. MEASUREMENTS AND MAIN RESULTS: The main outcome measurement was time to first protease inhibitor prescription after first elevated HIV viral load (>10,000 copies/ml). In this cohort, 190 patients had an elevated viral load (median age 39; 87% male; 12% history of injection drug use; 63% AIDS; 53% with depression; 17% history of pneumocystis pneumonia; 54% CD4 <200). In Cox proportional hazards modeling, significant univariate correlates for delayed protease inhibitor initiation were higher CD4 cell count (hazard ratio [HR] 2.38 for CD4 200–500 compared with <200, 95% confidence interval [CI] 1.59, 3.57; and HR 8.33 for CD4 >500; 95% CI 2.63, 25.0), higher viral load (HR 0.43 for each 10-fold increase; 95% CI 0.31, 0.59), injection drug use (HR 2.08; 95% CI 1.05, 4.17), AIDS (HR 0.24; 95% CI 0.15, 0.36), and history of pneumocystis pneumonia (HR 0.32; 95% CI 0.21, 0.49). In multivariate models adjusted for secular trends in protease inhibitor use, factors significantly associated with delay of protease inhibitor initiation (p<.05) were higher CD4 cell count (for CD4 200–500, HR 2.63; 95% CI 1.61, 4.17; for CD4 >500, HR 11.11; 95% CI 3.57, 33.33), higher viral load (HR 0.66 for each 10-fold increase; 95% CI 0.45, 0.98), history of pneumocystis pneumonia (HR 0.57; 95% CI 0.37, 0.90), history of depression (HR 1.49; 95% CI 1.03, 2.13), and history of injection drug use (HR 2.70; 95% CI 1.35, 5.56). CONCLUSIONS: HIV-infected patients with higher CD4 cell counts or a history of depression or history of injection drug use have significant and lengthy delays of protease inhibitor therapy. Although some delays may be clinically appropriate, enhancement of provider and patient education might prove beneficial. Further research should examine reasons for delays in protease inhibitor initiation and their appropriateness.

Factors associated with initiation of primary medical care for HIV-infected persons☆

PURPOSE To examine the degree of immune dysfunction of human immunodeficiency virus (HIV)-infected patients at the time of presentation and to identify factors associated with early and late initial primary medical care for HIV infection as measured by CD4+ lymphocyte count. PATIENTS AND METHODS Two hundred fifty-one consecutive outpatients without prior primary care for HIV infection were assessed at a municipal hospital HIV intake clinic (derivation group). Sociodemographic and clinical variables were examined for their association with CD4+ cell count on presentation in bivariate and stepwise linear regression analyses. Variables of interest were examined in 123 similar patients at a second site to assess the generalizability of our findings (validation group). RESULTS In the derivation group, 30% of patients presented for initial primary care with CD4+ cell counts less than 200/mm3, 51% had counts from 201/mm3 to 500/mm3, and only 19% had counts greater than 500/mm3. Twenty-seven percent of patients had delayed seeking medical care for longer than 1 year and 12%, for more than 2 years after an initial positive HIV serologic evaluation. Three variables were significant and independent predictors of CD4+ cell count on presentation: Haitian ethnicity (P = 0.05) and HIV-related symptoms (P = 0.005) were associated with lower CD4+ cell counts; and female sex (P = 0.009) was associated with higher CD4+ cell counts. With HIV-related symptoms excluded from the model, a history of cocaine use was also a significant predictor for higher CD4+ cell count (P = 0.02). In the validation group, which included few Haitians, results for female sex and HIV-related symptoms showed a similar association. CONCLUSIONS Most HIV-infected patients presented for primary care with advanced immune dysfunction. A substantial percentage of patients waited over a year to initiate medical care after testing positive for HIV. Haitian patients presented later for primary HIV care as measured by CD4+ cell count. Women presented with significantly higher CD4+ cell counts than did men. Since few characteristics examined could clearly identify the majority of late-presenting HIV-infected patients, improved general and targeted efforts are needed to link all HIV-infected people with primary medical care before the development of advanced disease.

Recent drug use, homelessness and increased short-term mortality in HIV-infected persons with alcohol problems

Objective:To assess the impact of recent heavy alcohol use, heroin/cocaine use, and homelessness on short-term mortality in HIV-infected persons. Methods:Survival in a longitudinal cohort of 595 HIV-infected persons with alcohol problems was assessed at 6-month intervals in 1996–2005. The time-varying main independent variables were heavy alcohol use (past 30 days), heroin/cocaine use (past 6 months), and homelessness (past 6 months). Date of death was determined using the Social Security Death Index. Outcomes were limited to deaths occurring within 6 months of last assessment to ensure recent assessments of the main independent variables. Cox proportional hazards models were fit to the data. Results:Death within 6 months of their last assessment occurred in 31 subjects (5.2%). Characteristics at study entry included mean age 41 years, 25% female, 41% African-American, 24% with CD4 cell count < 200 cells/μl; 41% taking antiretroviral therapy, 30% heavy alcohol use, 57% heroin or cocaine use, and 28% homelessness. Heroin or cocaine use [hazard ratio (HR), 2.43; 95% confidence interval (CI), 1.12–5.30)] and homelessness (HR, 2.92; 95% CI, 1.32–6.44), but not heavy alcohol use (HR, 0.57; 95% CI, 0.23–1.44), were associated with increased mortality in analyses adjusted for age, injection drug use ever, CD4 cell count, and current antiretroviral therapy. Conclusions:Recent heroin or cocaine use and homelessness are associated with increased short-term mortality in HIV-infected patients with alcohol problems. Optimal management of HIV-infected patients requires regular assessments for drug use and homelessness and improved access to drug treatment and housing.

Factors associated with discontinuation of antiretroviral therapy in HIV-infected patients with alcohol problems

Abstract Although mortality rates among HIV-infected populations have declined with the advent of combination antiretroviral therapy (ART), patients with substance use disorders have benefited less from these therapies. While adherence to ART has been well studied, less is known about factors associated with discontinuation of ART. The aim of this study is to investigate predictors of discontinuation of ART in HIV-infected patients with alcohol problems, focusing on their substance use and depressive symptoms. The study cohort (n=266) was prospectively assessed with biannual standardised interviews between 2001 and 2005. Four predictor variables (cocaine, heroin, heavy alcohol use and substantial depressive symptoms) were assessed six months prior to the outcome (ART discontinuation). Longitudinal logistic regression models examined the association between predictor variables and ART discontinuation adjusting for age, gender, race/ethnicity, homelessness, CD4, HIV RNA and HIV Symptom Index. Subjects were 77% male; 43% black; 22% homeless; 45% used cocaine; 20% used heroin; 29% had heavy alcohol use; and 40% had substantial depressive symptoms. Discontinuation occurred in 135 (17%) of the observations (n=743). In bivariate analyses, cocaine use, heroin use and depressive symptoms were significantly associated with ART discontinuation but heavy alcohol use was not. In the multivariable model, substantial depressive symptoms (adjusted odds ratio (AOR)=1.66; 95% confidence interval (CI): 1.04, 2.65) but not cocaine (AOR=1.28; 95%CI: 0.76, 2.16) or heroin use (AOR=1.27 95%CI: 0.66, 2.44), remained significantly associated with ART discontinuation. Among HIV-infected adults with alcohol problems, depressive symptoms, but not substance use, predicted subsequent ART discontinuation. Recognition and treatment of depressive symptoms in this population may result in better maintenance of ART and its associated clinical benefits.

The impact of alcohol use on depressive symptoms in human immunodeficiency virus-infected patients

AIMS To examine the impact of alcohol use on depressive symptoms in human immunodeficiency virus (HIV)-infected patients. DESIGN Data were collected at 6-month intervals and analyzed to evaluate the association between alcohol dependence and consumption on depressive symptoms using longitudinal mixed-effects regression models controlling for specified covariates. MEASUREMENTS The two independent variables were current alcohol dependence assessed using the Composite International Diagnostic Interview (CIDI) and past month consumption (heavy versus not heavy drinking) using a validated calendar-based method. The primary outcome was depressive symptoms as measured by the Center for Epidemiologic Studies Depression Scale (CES-D). PARTICIPANTS HIV-infected adults with current or past alcohol problems. FINDINGS Alcohol dependence and heavy alcohol use were significantly associated with higher CES-D scores in unadjusted models. In adjusted analyses, the association of current alcohol dependence persisted [mean difference in CES-D was 3.49 for dependence versus non-dependence; 95% confidence interval (CI): 1.76-5.22]; however, the effect of heavy drinking was no longer statistically significant (mean difference in CES-D was 1.04 for heavy versus not heavy drinking; 95% CI: -0.24-2.32). CONCLUSIONS Alcohol use is associated with more depressive symptoms in HIV-infected patients with alcohol problems. This association remains significant after adjusting for potential confounders only when alcohol use meets the criteria for alcohol dependence.

Awareness of Hepatitis C Diagnosis is Associated with Less Alcohol Use Among Persons Co-Infected with HIV

BACKGROUND AND OBJECTIVEIt is unknown whether testing HIV-infected individuals for hepatitis C virus (HCV) and informing them of their HCV status impacts subsequent alcohol use. We hypothesized that HIV-infected individuals with current or past alcohol problems who reported being told they had HCV were more likely to 1) abstain from alcohol and 2) not drink unhealthy amounts compared to individuals who had not been told.DESIGN, PARTICIPANTS, AND MEASUREMENTSData from a prospective, observational cohort study (HIV-Longitudinal Interrelationships of Viruses and Ethanol) were used to assess the association between awareness of having HCV at baseline and subsequent abstinence and not drinking unhealthy amounts as reported at 6-month follow-up intervals. General estimating equations logistic regression was used to account for the correlation from using repeated observations from the same subject over time. We adjusted for age, sex, race, homelessness, injection drug use, depressive symptoms, and having abnormal liver tests.RESULTSParticipants who reported being told they had HCV were more likely to report abstaining from alcohol (AOR = 1.60; 95% CI: 1.13 to 2.27) and not drinking unhealthy amounts (AOR = 1.46; 95% CI: 1.01 to 2.11).CONCLUSIONSAmong patients infected with HIV who had a history of alcohol problems, reporting being told one had HCV was associated with greater abstinence from alcohol and less unhealthy amounts of drinking.

Alcohol Consumption and Lipodystrophy in HIV-infected Adults with Alcohol Problems

Lipodystrophy is a common long-term complication of HIV infection that may lead to decreased quality of life and less adherence to antiretroviral therapy (ART). A complete understanding of the etiology of HIV-associated lipodystrophy has not yet been achieved, although factors related to the virus, per se, and use of ART appear to be related. Alcohol use is common among HIV-infected patients and has biological effects on fat distribution, yet alcohols relationship to HIV-associated lipodystrophy has not been examined. The goal of this clinical study was to assess the effect of alcohol consumption on lipodystrophy in HIV-infected adults with alcohol problems. This was a prospective study (2001-2006) of 289 HIV-infected persons with alcohol problems. The primary outcome was self-reported lipodystrophy, which was assessed at one time point (median 29 months after enrollment). Alcohol use was assessed every 6 months and classified as: abstinent at all interviews; > or = 1 report of moderate drinking but no heavy drinking; 1 or 2 reports of heavy drinking; or > or = 3 reports of heavy drinking. Multivariable logistic regression models were fit to the data. Fifty-two percent (150/289) of subjects reported lipodystrophy. Alcohol consumption was: 34% abstinent at all interviews; 12% > or = 1 report of moderate drinking, but no heavy drinking; 34% 1-2 reports of heavy drinking; and 20% > or = 3 reports of heavy drinking. Although not statistically significant, subjects with alcohol use had a higher odds of lipodystrophy (adjusted odds ratios and 95% confidence interval: > or = 1 report of moderate drinking, 2.36 [0.89, 6.24]; 1-2 reports of heavy drinking, 1.34 [0.69, 2.60]; > or = 3 reports of heavy drinking, 2.07 [0.90, 4.73]). Alcohol use may increase the odds of developing HIV-associated lipodystrophy among subjects with alcohol problems. However, larger studies are needed to fully elucidate the role and impact of alcohol consumption on the development of this common long-term complication of HIV infection and its treatment.

Hepatitis C Infection is Associated with Depressive Symptoms in HIV-Infected Adults with Alcohol Problems

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