Associations of marijuana with markers of chronic lung disease in people living with HIV.

OBJECTIVES: The relationship between marijuana use and markers of chronic lung disease in people living with HIV (PLWH) is poorly understood. METHODS: We performed a cross-sectional analysis of the Examinations of HIV-Associated Lung Emphysema (EXHALE) study, including 162 HIV-positive patients and 138 participants without HIV. We modelled marijuana exposure as: (i) current daily or weekly marijuana smoking vs. monthly or less often; or (ii) cumulative marijuana smoking (joint-years). Linear and logistic regression estimated associations between marijuana exposure and markers of lung disease, adjusted for tobacco smoking and other factors. RESULTS: In PLWH, current daily or weekly marijuana use was associated with a larger forced vital capacity (FVC), larger total lung capacity and increased odds of radiographic emphysema compared with marijuana non-smokers in adjusted models; these associations were not statistically significant in participants without HIV. Marijuana joint-years were associated with higher forced expiratory volume in 1 s and FVC in PLWH but not with emphysema. CONCLUSIONS: In PLWH, marijuana smoking was associated with higher lung volumes and potentially with radiographic emphysema. No consistently negative associations were observed between marijuana and measures of chronic lung health.

Depression and all-cause mortality risk in HIV-infected and HIV-uninfected US veterans: a cohort study.

OBJECTIVES: The contribution of depression to mortality in adults with and without HIV infection is unclear. We hypothesized that depression increases mortality risk and that this association is stronger among those with HIV infection. METHODS: Veterans Aging Cohort Study (VACS) data were analysed from the first clinic visit on or after 1 April 2003 (baseline) to 30 September 2015. Depression definitions were: (1) major depressive disorder defined using International Classification of Diseases, Ninth Revision (ICD-9) codes; (2) depressive symptoms defined as Patient Health Questionnaire (PHQ)-9 scores ≥ 10. The outcome was all-cause mortality. Covariates were demographics, comorbid conditions and health behaviours. RESULTS: Among 129 140 eligible participants, 30% had HIV infection, 16% had a major depressive disorder diagnosis, and 24% died over a median follow-up time of 11 years. The death rate was 25.3 [95% confidence interval (CI) 25.0-25.6] deaths per 1000 person-years. Major depressive disorder was associated with mortality [hazard ratio (HR) 1.04; 95% CI 1.01, 1.07]. This association was modified by HIV status (interaction P-value = 0.02). In HIV-stratified analyses, depression was significantly associated with mortality among HIV-uninfected veterans but not among those with HIV infection. Among those with PHQ-9 data (n = 7372), 50% had HIV infection, 22% had PHQ-9 scores ≥ 10, and 28% died over a median follow-up time of 12 years. The death rate was 27.3 (95% CI 26.1-28.5) per 1000 person-years. Depressive symptoms were associated with mortality (HR 1.16; 95% CI 1.04, 1.28). This association was modified by HIV status (interaction P-value = 0.05). In HIV-stratified analyses, depressive symptoms were significantly associated with mortality among veterans with HIV infection but not among those without HIV infection. CONCLUSIONS: Depression was associated with all-cause mortality. This association was modified by HIV status and method of depression ascertainment.

The impact of prescribed opioids on CD4 cell count recovery among HIV-infected patients newly initiating antiretroviral therapy.

OBJECTIVES: Certain prescribed opioids have immunosuppressive properties, yet their impact on clinically relevant outcomes, including antiretroviral therapy (ART) response among HIV-infected patients, remains understudied. METHODS: Using the Veterans Aging Cohort Study data, we conducted a longitudinal analysis of 4358 HIV-infected patients initiating ART between 2002 and 2010 and then followed them for 24 months. The primary independent variable was prescribed opioid duration, categorized using pharmacy data as none prescribed, short-term (< 90 days) and long-term (≥ 90 days). Outcomes included CD4 cell count over time. Analyses adjusted for demographics, comorbid conditions, ART type and year of initiation, and overall disease severity [ascertained with the Veterans Aging Cohort Study (VACS) Index]. Sensitivity analyses examined whether effects varied according to baseline CD4 cell count, achievement of viral load suppression, and opioid properties (i.e. dose and known immunosuppressive properties). RESULTS: Compared to those with none, patients with short-term opioids had a similar increase in CD4 cell count (mean rise per year: 74 vs. 68 cells/µL; P = 0.11), as did those with long-term prescribed opioids (mean rise per year: 74 vs. 75 cells/µL; P = 0.98). In sensitivity analysis, compared with no opioids, the effects of short-term prescribed opioids were statistically significant among those with a baseline CD4 cell count ≥ 500 cells/µL (mean rise per year: 52 cells/µL for no opioids vs. 20 cells/µL for short-term opioids; P = 0.04); findings were otherwise unchanged. CONCLUSIONS: Despite immunosuppressive properties intrinsic to opioids, prescribed opioids appeared to have no effect on CD4 cell counts over 24 months among HIV-infected patients initiating ART.

Impact of defined clinical population and missing data on temporal trends in HIV viral load estimation within a health care system.

OBJECTIVES: Community viral load (CVL) estimates vary based on analytic methods. We extended the CVL concept and used data from the Veterans Health Administration (VA) to determine trends in the health care system viral load (HSVL) and its sensitivity to varying definitions of the clinical population and assumptions regarding missing data. METHODS: We included HIV-infected patients in the Veterans Aging Cohort Study, 2000-2010, with at least one documented CD4 count, HIV-1 RNA or antiretroviral prescription (n = 37 318). We created 6-month intervals including patients with at least one visit in the past 2 years. We assessed temporal trends in clinical population size, patient clinical status and mean HSVL and explored the impact of varying definitions of the clinical population and assumptions about missing viral load. RESULTS: The clinical population size varied by definition, increasing from 16 000-19 000 patients in 2000 to 23 000-26 000 in 2010. The proportion of patients with suppressed HIV-1 RNA increased over time. Over 20% of patients had no viral load measured in a given interval or the past 2 years. Among patients with a current HIV-1 RNA, mean HSVL decreased from 97 800 HIV-1 RNA copies/mL in 2000 to 2000 copies/mL in 2010. When current HIV-1 RNA data were unavailable and the HSVL was recalculated using the last available HIV-1 RNA, HSVL decreased from 322 300 to 9900 copies/mL. HSVL was underestimated when using only current data in each interval. CONCLUSIONS: The CVL concept can be applied to a health care system, providing a measure of health care quality. Like CVL, HSVL estimates depend on definitions of the clinical population and assumptions about missing data.

Prevalence and correlates of obstructive sleep apnoea among patients with and without HIV infection.

OBJECTIVES: In HIV-uninfected populations, obstructive sleep apnoea (OSA) is commonly associated with cardiovascular disease, metabolic syndrome, and cognitive impairment. These comorbidities are common in HIV-infected patients, but there are scarce data regarding OSA in HIV-infected patients. Therefore, we examined the prevalence and correlates of OSA in a cohort of HIV-infected and uninfected patients. METHODS: An observational cohort study was carried out. Electronic medical record and self-report data were examined in patients enrolled in the Veterans Aging Cohort Study (VACS) between 2002 and 2008 and followed until 2010. The primary outcome was OSA diagnosis, determined using International Classification of Diseases, 9th edition (ICD-9) codes, in HIV-infected compared with uninfected individuals. We used regression analyses to determine the association between OSA diagnosis, symptoms and comorbidities in adjusted models. RESULTS: Of 3683 HIV-infected and 3641 uninfected patients, 143 (3.9%) and 453 (12.4%) had a diagnosis of OSA (p<0.0001), respectively. HIV-infected patients were more likely to report symptoms associated with OSA such as tiredness and fatigue. Compared with uninfected patients with OSA, HIV-infected patients with OSA were younger, had lower body mass indexes (BMIs), and were less likely to have hypertension. In models adjusting for these traditional OSA risk factors, HIV infection was associated with markedly reduced odds of OSA diagnosis (odds ratio 0.48; 95% confidence interval 0.39-0.60). CONCLUSIONS: HIV-infected patients are less likely to receive a diagnosis of OSA. Future studies are needed to determine whether the lower prevalence of OSA diagnoses in HIV-infected patients is attributable to decreased screening and detection or to a truly decreased likelihood of OSA in the setting of HIV infection.

Intention to adhere to HIV treatment: a patient-centred predictor of antiretroviral adherence.

OBJECTIVES: Despite the effectiveness of highly active antiretroviral therapy (HAART), HIV remains a major cause of mortality in the USA, largely as a result of poor HIV treatment adherence. In this study we assessed the association between five patient-centred factors and adherence to HIV treatment. METHODS: We surveyed 244 adults at two HIV clinics in Houston, Texas between October 2009 and April 2010. Participants were given a questionnaire and their charts were reviewed for clinical data. Survey items assessed the following factors: self-assessed HIV knowledge, awareness of disease biomarkers, intention to adhere to HIV treatment, health literacy and decision-making style. The primary outcome measure was HAART adherence during the previous month. Logistic regressions were performed to calculate the effect of each factor on adherence. RESULTS: All participants had HIV/AIDS and were on HAART at enrolment. Eight per cent of participants were female, 57% were African-American and 16% were Hispanic. Mean age was 58.1 years. Sixty-eight per cent were adherent to HAART during the last month. On univariate analysis, a preference for wanting choices, correct knowledge of recent HIV viral load level, and intention to adhere to HIV treatment were significantly associated with adherence. On multivariate analysis, only intention to adhere to HIV treatment remained statistically significant after adjusting for other factors (odds ratio 2.2; 95% confidence interval 1.1 to 4.3). CONCLUSIONS: Intention to adhere to HIV treatment was significantly associated with self-reported adherence to HAART. Interventions that bolster patients' intentions to adhere to HIV treatment during clinical encounters may improve adherence to HAART and HIV control.

Hazardous drinking and its association with homelessness among veterans in care.

BACKGROUND: While scholarship on alcohol use and homelessness has focused on the impact of alcohol abuse and dependence, little is known about the effects of lower levels of misuse such as hazardous use. Veterans receiving care in the Department of Veterans Affairs Health Care System (VA) constitute a population that is vulnerable to alcohol misuse and homelessness. This research examines the effects of hazardous drinking on homelessness in the Veterans Aging Cohort Study, a sample of 2898 older veterans (mean age=50.2), receiving care in 8 VAs across the country. METHODS: Logistic regression models examined the associations between (1) hazardous drinking at baseline and homelessness at 1-year follow-up, (2) transitions into and out of hazardous drinking from baseline to follow-up and homelessness at follow-up, and (3) transitioning to hazardous drinking and transitioning to homelessness from baseline to follow-up during that same time-period. RESULTS: After controlling for other correlates including alcohol dependence, hazardous drinking at baseline increased the risk of homelessness at follow-up (adjusted odds ratio [AOR]=1.39, 95% confidence interval [CI]=1.02, 1.88). Transitioning to hazardous drinking more than doubled the risk of homelessness at follow-up (AOR=2.42, 95% CI=1.41, 4.15), while more than doubling the risk of transitioning from being housed at baseline to being homeless at follow-up (AOR=2.49, 95% CI=1.30, 4.79). CONCLUSIONS: Early intervention that seeks to prevent transitioning into hazardous drinking could increase housing stability among veterans. Brief interventions which have been shown to be effective at lower levels of alcohol use should be implemented with veterans in VA care.

Towards a combined prognostic index for survival in HIV infection: the role of 'non-HIV' biomarkers.

BACKGROUND: As those with HIV infection live longer, 'non-AIDS' condition associated with immunodeficiency and chronic inflammation are more common. We ask whether 'non-HIV' biomarkers improve differentiation of mortality risk among individuals initiating combination antiretroviral therapy (cART). METHODS: Using Poisson models, we analysed data from the Veterans Aging Cohort Study (VACS) on HIV-infected veterans initiating cART between 1 January 1997 and 1 August 2002. Measurements included: HIV biomarkers (CD4 cell count, HIV RNA and AIDS-defining conditions); 'non-HIV' biomarkers (haemoglobin, transaminases, platelets, creatinine, and hepatitis B and C serology); substance abuse or dependence (alcohol or drug); and age. Outcome was all cause mortality. We tested the discrimination (C statistics) of each biomarker group alone and in combination in development and validation data sets, over a range of survival intervals, and adjusting for missing data. RESULTS: Of veterans initiating cART, 9784 (72%) had complete data. Of these, 2566 died. Subjects were middle-aged (median age 45 years), mainly male (98%) and predominantly black (51%). HIV and 'non-HIV' markers were associated with each other (P < 0.0001) and discriminated mortality (C statistics 0.68-0.73); when combined, discrimination improved (P < 0.0001). Discrimination for the VACS Index was greater for shorter survival intervals [30-day C statistic 0.86, 95% confidence interval (CI) 0.80-0.91], but good for intervals of up to 8 years (C statistic 0.73, 95% CI 0.72-0.74). Results were robust to adjustment for missing data. CONCLUSIONS: When added to HIV biomarkers, 'non-HIV' biomarkers improve differentiation of mortality. When evaluated over similar intervals, the VACS Index discriminates as well as other established indices. After further validation, the VACS Index may provide a useful, integrated risk assessment for management and research.

Hepatitis C virus infection-related morbidity and mortality among patients with human immunodeficiency virus infection.

Hepatitis C virus (HCV) has emerged as a major pathogen among patients with human immunodeficiency virus (HIV). Morbidity and mortality were compared among 263 patients with HIV alone, 166 patients with HIV and HCV, and 60 patients with HCV alone (mean duration of follow-up, 2 years and 10 months). No differences in HIV loads and CD4 cells counts were observed between the HIV and HIV/HCV groups. Alanine aminotransferase levels were higher (52 U/L versus 35 U/L; P<.05) and albumin levels were lower (3.5 g/dL versus 3.8 g/dL; P <.02) among coinfected patients than they were among patients with HIV alone. Liver decompensation developed in 10% of patients with HIV/HCV coinfection. In contrast, no liver-related deaths or decompensation occurred in patients without coinfection (P<.05). Of the patients with HIV alone, 7% died, compared with 11% of the coinfected patients (P<.02); 47% of the deaths in the latter group were due to liver-related causes. In summary, HCV infection causes increased morbidity and mortality in patients with HIV infection.

IgG responses to protein-conjugated pneumococcal capsular polysaccharides in persons who are genetically incapable of responding to unconjugated polysaccharides.

We have previously shown that the capacity to make IgG to pneumococcal capsular polysaccharides (PCPs) is inherited as an autosomal, mixed codominant trait. The purpose of this study was to determine whether this genetically determined unresponsiveness could be overcome by injection of protein-conjugated pneumococcal vaccines. Seven healthy adults who had failed to produce IgG to five or more of 10 representative PCPs after receiving pneumococcal vaccine and whose parents, siblings, and/or offspring had a similar lack of responsiveness received a series of protein-conjugated polysaccharide vaccines. Excellent IgG responses to most of the PCPs tested were eventually observed in five of the seven subjects after they received octavalent diphtheria toxoid-conjugated vaccine. Administration of certain protein-conjugated PCPs leads to IgG responses in some persons who lack the capacity to respond to unconjugated PCPs.

Human antibodies elicited by a pneumococcal vaccine express idiotypic determinants indicative of V(H)3 gene segment usage.

Human immunodeficiency virus (HIV)-infected persons manifest decreased antibody responses to pneumococcal polysaccharide vaccines. Since human antibody responses to polysaccharides are often restricted, the molecular structure of antibodies elicited by a 23-valent pneumococcal vaccine was analyzed. Anti-idiotypic reagents were used to detect V(H)1, V(H)3, and V(H)4 gene usage by antibodies to pneumococcal capsular polysaccharides in HIV-uninfected and HIV-infected subjects by ELISA. HIV-uninfected persons generated beta-mercaptoethanol-sensitive and -resistant antibodies to pneumococcal capsular polysaccharides expressing V(H)3 determinants recognized by the D12, 16.84, and B6 monoclonal antibodies; antibodies expressing V(H)1 determinants were not detected, and V(H)4 determinants were expressed by beta-mercaptoethanol-sensitive antibodies only; and HIV-infected subjects had significantly lower capsular polysaccharide-specific and V(H)3-positive antibody responses. These findings confirm decreased antibody responses to pneumococcal vaccination in HIV-infected persons and suggest that their poor responses may result from HIV-associated depletion of restricted B cell subsets.

Molecular epidemiology of bartonella infections in patients with bacillary angiomatosis-peliosis.

BACKGROUND: Bacillary angiomatosis and bacillary peliosis are vascular proliferative manifestations of infection with species of the genus bartonella that occur predominantly in patients infected with the human immunodeficiency virus. Two species, B. henselae and B. quintana, have been associated with bacillary angiomatosis, but culture and speciation are difficult, and there has been little systematic evaluation of the species-specific disease characteristics. We studied 49 patients seen over eight years who were infected with bartonella species identified by molecular techniques and who had clinical lesions consistent with bacillary angiomatosis-peliosis. METHODS: In this case-control study, a standardized questionnaire about exposures was administered to patients with bacillary angiomatosis-peliosis and to 96 matched controls. The infecting bartonella species were determined by molecular techniques. RESULTS: Of the 49 patients with bacillary angiomatosis-peliosis, 26 (53 percent) were infected with B. henselae and 23 (47 percent) with B. quintana. Subcutaneous and lytic bone lesions were strongly associated with B. quintana, whereas peliosis hepatis was associated exclusively with B. henselae. Patients with B. henselae infection were identified throughout the study period and were epidemiologically linked to cat and flea exposure (P< or =0.004), whereas those with B. quintana were clustered and were characterized by low income (P=0.003), homelessness (P = 0.004), and exposure to lice (P= 0.03). Prior treatment with macrolide antibiotics appeared to be protective against infection with either species. CONCLUSIONS: B. henselae and B. quintana, the organisms that cause bacillary angiomatosis-peliosis, are associated with different epidemiologic risk factors and with predilections for involvement of different organs.

BOX-polymerase chain reaction-based DNA analysis of nonserotypeable Streptococcus pneumoniae implicated in outbreaks of conjunctivitis.

Nonserotypeable isolates predominate in epidemic conjunctivitis caused by Streptococcus pneumoniae. Previous evaluations of outbreaks of pneumococcal conjunctivitis have relied on epidemiologic factors and the nontypeability of the isolates to infer that a single clone was involved. In the present study, BOX-polymerase chain reaction DNA analysis was used to characterize nonserotypeable S. pneumoniae isolated by conjunctival culture during a recent conjunctivitis outbreak and to compare these isolates with those from outbreaks described earlier. The recent outbreak was caused by a single pneumococcal clone. Outbreaks in separate parts of the United States in 1980-1981 were all caused by the same clone. Cluster analysis revealed a high degree of genetic relatedness among isolates causing conjunctivitis compared with that among other nonserotypeable S. pneumoniae, with the closest relatedness being found among the 1996 and 1980-1981 conjunctival isolates.

Colonization by Streptococcus pneumoniae among human immunodeficiency virus-infected adults: prevalence of antibiotic resistance, impact of immunization, and characterization by polymerase chain reaction with BOX primers of isolates from persistent S. pneumoniae carriers.

Pharyngeal colonization by Streptococcus pneumoniae was evaluated in 103 human immunodeficiency virus (HIV)-infected subjects (<200 CD4 cells/microL, 57; > or = 200 CD4 cells/microL, 46) and 39 non-HIV-infected controls who were participants in a vaccine study. At baseline, 7%, 20%, and 10% of subjects in the <200 and > or = 200 CD4 cell groups and in the control group were colonized with S. pneumoniae: Rates at 6 months were 23%, 22%, and 0%, respectively. Of 34 isolates from HIV-infected subjects, 25 were penicillin-resistant and 19 were resistant to > or = 3 antimicrobials; of 8 isolates from controls, 1 was resistant. Resistance to trimethoprim-sulfamethoxazole was significantly higher among HIV-infected subjects with <200 CD4 cells/microL than in those with more CD4 cells. Polymerase chain reaction DNA analysis with BOX primers demonstrated that 12 HIV-infected subjects were persistently colonized with the same S. pneumoniae strain for > or = 1 month compared with none of the controls. HIV-infected subjects were more likely to be persistent pneumococcal carriers and to carry antibiotic-resistant isolates than were non-HIV-infected subjects.

Genetic regulation of the capacity to make immunoglobulin G to pneumococcal capsular polysaccharides.

BACKGROUND: Genetic regulation of immunoglobulin G(IgG) responses to pneumococcal capsular polysaccharides (PPS), has been demonstrated in mice but not in humans. Earlier studies from this laboratory showed that healthy adults have a varying capacity to generate IgG antibody to PPS; this study sought to determine whether this capacity is genetically controlled. METHODS: A 23-valent pneumococcal vaccine was administered to 72 unrelated White adults, 4 nuclear families, and 61 members of an extended Ashkenazic Jewish family. Selected individuals later received one or more doses of the vaccine and/or a single dose of protein-conjugated PPS. Four to six weeks after each vaccination, IgG to PPS was measured by ELISA. Immunoglobulin allotypes and HLA types were determined by standard techniques. RESULTS: After vaccination, 53% of the 72 unrelated White adults had measurable levels of IgG antibody to all of 10 PPS studied (high-level responders), 36% had IgG to 6-9 PPS, and 11% had IgG to < or = 5 of 10 PPS (low-level responders). Persons who did not make IgG to an individual PPS also failed to make IgM or IgA to that antigen. Low-level responders had reduced mean IgG levels to PPS to which they did make IgG; nevertheless, their total serum concentrations of IgG, IgG2, IgA, and IgM were normal, and each made IgG2 to at least one PPS, all indicating that a global defect in Ig production was not responsible. The responder status of offspring was highly associated with that of their parents. Segregation analysis of 61 Ashkenazic family members revealed that the capacity to generate anti-PPS IgG was inherited in a mixed, codominant fashion. Repeated vaccination or administration of protein-conjugated PPS did not elicit measurable IgG in nonresponders. The HLA type was not associated with antibody responses. An association between IgG level and Gm(23)+ allotype was observed in unrelated Whites but not in Ashkenazic Jews. CONCLUSIONS: Thus, humans exhibit a variable capacity to respond to PPS. This response is hereditable in a mixed, codominant fashion. The absence of IgG to a PPS, even after antigen is presented in a protein-conjugate form, may reflect a genetically mediated failure to recognize polysaccharide antigens. Since persons who respond to fewer PPS also have lower levels of IgG to PPS to which they do respond, genetically determined deficiencies in events that involve proliferation of committed B lymphocytes may also play a role.

Diagnosing and treating cytomegalovirus pneumonia in patients with AIDS.

Because cytomegalovirus (CMV) can be isolated from pulmonary secretions of human immunodeficiency virus (HIV)-infected patients without causing disease, its clinical significance as a cause of pneumonia in this patient population is frequently questioned. In a 22-month period, CMV pneumonia was diagnosed in 17 (8%) of 210 HIV-infected patients who underwent lung biopsy on the basis of microbiological and histologic criteria. The clinical presentations of these patients were nonspecific, including fever (100% of patients), shortness of breath (71%), cough (76%), and Pao2 of < 75 mm Hg (88%). A high correlation in the degree of viral burden in lung biopsy specimens was demonstrated by histologic examination, immunohistochemical analysis, and in situ hybridization. No other pulmonary pathogens were identified for nine patients, whereas other possible causes of pneumonia were present in eight: 11 patients had evidence of extrapulmonary CMV disease at presentation. Most patients initially responded to specific anti-CMV therapy; the overall mean survival +/- SD was 3.1 +/- 2.5 months. CMV should be considered as a possible cause of pneumonia in patients with advanced AIDS especially if CMV infection is documented at other sites.

IgG antibody to pneumococcal capsular polysaccharide in human immunodeficiency virus-infected subjects: persistence of antibody in responders, revaccination in nonresponders, and relationship of immunoglobulin allotype to response.

Human immunodeficiency virus (HIV)-infected persons are less likely than are noninfected persons to respond to vaccination with pneumococcal polysaccharides (PPS). Among those who respond, however, similar IgG levels may be achieved. HIV-infected men immunized with pneumococcal vaccine were classified as high- or low-level responders (IgG > or = 1 microgram/mL for > or = 3 of 5 PPS [high] or for < or = 1 PPS [low]). One and 2 years after immunization, geometric mean IgG levels and the percentages of subjects with IgG levels > or = 1 microgram/mL were similar for HIV-infected and for healthy high-level responders (controls) for all PPS except for serotype 8. Among HIV-infected low-level responders, revaccination with a double dose of pneumococcal vaccine did not stimulate IgG responses. Responsiveness of HIV-infected white patients was significantly associated with the Km(1)- negative allotype. These findings support current general recommended guidelines for administering pneumococcal vaccine to HIV-infected persons. Nonresponders will not benefit from revaccination.