[Show abstract][Hide abstract] ABSTRACT: Immunoglobulin (Ig)G levels are important for antibody vaccine responses and IgG subclass deficiencies have been associated with severe 2009 influenza A (H1N1) infections. Studies have demonstrated variations in immune responses to the H1N1 vaccine, but the aetiology of this is unknown. We determined the associations between pre-vaccination overall and influenza-specific IgG subclass levels and 2009 H1N1-specific antibody responses post-vaccination (robust versus poor at day 28) stratified by human immunodeficiency virus (HIV) status. Logistic regression models were utilized to evaluate whether pre-vaccination IgG subclass levels were associated with the antibody response generated post-vaccination. We evaluated 48 participants as part of a clinical study who were stratified by robust versus poor post-vaccination immune responses. Participants had a median age of 35 years; 92% were male and 44% were Caucasian. HIV-infected adults had a median CD4 count of 669 cells/mm(3) , and 79% were receiving highly active anti-retroviral therapy. HIV-infected participants were more likely to have IgG2 deficiency (<240 mg/dl) than HIV-uninfected individuals (62% versus 4%, P < 0·001). No association of pre-vaccination IgG subclass levels (total or influenza-specific) and the antibody response generated by HIN1 vaccination in either group was found. In summary, pre-vaccination IgG subclass levels did not correlate with the ability to develop robust antibody responses to the 2009 influenza A (H1N1) monovalent vaccine. IgG2 deficiencies were common among HIV-infected individuals but did not correlate with poor influenza vaccine responses. Further investigations into the aetiology of disparate vaccine responses are needed.
[Show abstract][Hide abstract] ABSTRACT: Cardiovascular disease is an increasing concern among HIV-infected persons and their providers. We determined if fatty liver disease is a marker for underlying coronary atherosclerosis among HIV-infected persons.
We performed a cross-sectional study in HIV-infected adults to evaluate the prevalence of and factors, including fatty liver disease, associated with subclinical coronary atherosclerosis. All participants underwent computed tomography for determination of coronary artery calcium (CAC; positive defined as a score >0) and fatty liver disease (defined as a liver-to-spleen ratio <1.0). Factors associated with CAC were determined using multivariate logistic regression models.
We included in the study 223 HIV-infected adults with a median age of 43 years [interquartile range (IQR) 36-50 years]; 96% were male and 49% were Caucasian. The median CD4 count was 586 cells/μL and 83% were receiving antiretroviral medications. Seventy-five (34%) had a positive CAC score and 29 (13%) subjects had fatty liver disease. Among those with CAC scores of 0, 1-100 and >100, the percentage with concurrent fatty liver disease was 8, 18 and 41%, respectively (P=0.001). In the multivariate model, CAC was associated with increasing age [odds ratio (OR) 4.3 per 10 years; P<0.01], hypertension (OR 2.6; P<0.01) and fatty liver disease (OR 3.8; P<0.01).
Coronary atherosclerosis as detected using CAC is prevalent among young HIV-infected persons. The detection of fatty liver disease among HIV-infected adults should prompt consideration of assessment for underlying cardiovascular disease and risk factor reduction.
HIV Medicine 09/2011; 12(8):463-71. DOI:10.1111/j.1468-1293.2010.00904.x · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vaccination provides long-term immunity to hepatitis A virus (HAV) among the general population, but there are no such data regarding vaccine durability among human immunodeficiency virus (HIV)-infected adults.
We retrospectively studied HIV-infected adults who had received 2 doses of HAV vaccine. We analyzed blood specimens taken at 1 year, 3 years, and, when available, 6-10 years postvaccination. HAV immunoglobulin G (IgG) values of ≥10 mIU/mL were considered seropositive.
We evaluated specimens from 130 HIV-infected adults with a median age of 35 years and a median CD4 cell count of 461 cells/mm(3) at or before time of vaccination. Of these, 49% had an HIV RNA load <1000 copies/mL. Initial vaccine responses were achieved in 89% of HIV-infected adults (95% confidence interval [CI], 83%-94%), compared with 100% (95% CI, 99%-100%) of historical HIV-uninfected adults. Among initial HIV-infected responders with available specimens, 90% (104 of 116; 95% CI, 83%-95%) remained seropositive at 3 years and 85% (63 of 74; 95% CI, 75%-92%) at 6-10 years. Geometric mean concentrations (GMCs) among HIV-infected adults were 154, 111, and 64 mIU/mL at 1, 3, and 6-10 years, respectively, compared with 1734, 687, and 684 mIU/mL among HIV-uninfected persons. Higher GMCs over time among HIV-infected adults were associated with lower log(10) HIV RNA levels (β = -.12, P = .04).
Most adults with well-controlled HIV infections had durable seropositive responses up to 6-10 years after HAV vaccination. Suppressed HIV RNA levels are associated with durable HAV responses.
The Journal of Infectious Diseases 06/2011; 203(12):1815-23. DOI:10.1093/infdis/jir180 · 5.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) exhibit antiviral activity against human immunodeficiency virus type 1 (HIV-1) in vitro and may modulate the immune response to HIV infection. Studies evaluating the antiviral activity of statins have yielded conflicting results.
We conducted a randomized, double-blind, placebo-controlled crossover trial to investigate the effect of atorvastatin on HIV-1 RNA (primary objective) and cellular markers of immune activation (secondary objective). HIV-infected individuals not receiving antiretroviral therapy were randomized to receive either 8 weeks of atorvastatin (80 mg) or placebo daily. After a 4-6 week washout phase, participants switched treatment assignments. The study had 80% power to detect a 0.3 log(10) decrease in HIV-1 RNA level. Expression of CD38 and HLA-DR on CD4(+) and CD8(+) T cells was used to measure immune activation.
Of 24 randomized participants, 22 completed the study. Although HIV-1 RNA level was unaffected by the intervention (-0.13 log(10) copies/mL; P = .85), atorvastatin use resulted in reductions in circulating proportions of CD4(+) HLA-DR(+) (-2.5%; P = .02), CD8(+) HLA-DR(+) (-5%; P = .006), and CD8(+) HLA-DR(+) CD38(+) T cells (-3%; P = .03). Reductions in immune activation did not correlate with declines in serum levels of low-density lipoprotein cholesterol.
Short-term use of atorvastatin was associated with modest but statistically significant reductions in the proportion of activated T lymphocytes.
The Journal of Infectious Diseases 03/2011; 203(6):756-64. DOI:10.1093/infdis/jiq115 · 5.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human immunodeficiency virus (HIV)-infected persons are at risk for severe influenza infections. Although vaccination against the H1N1 pandemic influenza strain is recommended, currently there are no data on the durability of post-vaccination antibody responses in this population.
HIV-infected and HIV-uninfected adults (18-50 years old) received a single dose of monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009H1N1). Antibody levels to the 2009 H1N1 pandemic strain were determined at day 0, day 28, and 6 months by hemagglutination-inhibition assay. A seroprotective response was a post-vaccination titer of ≥1:40 among those with a pre-vaccination level of ≤1:10. Geometric mean titers (GMT) and factors associated with higher levels were also evaluated.
We studied 127 participants with a median age of 35 (interquartile range (IQR) 28, 42) years. Among the HIV-infected arm (n=63), the median CD4 count was 595 (IQR 476, 819)cells/mm(3) and 83% were receiving HAART. Thirty-five percent of all participants had a pre-vaccination level of >1:10. HIV-infected compared to HIV-uninfected adults were less likely to generate a seroprotective response at day 28 (54% vs. 75%, adjusted OR 0.23, p=0.021) or have a durable response at 6 months post-vaccination (28% vs. 56%, adjusted OR 0.19, p=0.005). Additionally, although pre-vaccination GMT were similar in both arms (median 7 vs. 8, p=0.11), the GMT at 6 months was significantly lower among HIV-infected versus HIV-uninfected adults (median 20 vs. 113, p=0.003). Among HIV-infected persons, younger age (p=0.035) and receipt of HAART (p=0.028) were associated with higher GMTs at 6 months.
Despite vaccination, most HIV-infected adults do not generate durable seroprotective antibody responses to the 2009 influenza A (H1N1) virus, and hence may remain vulnerable to infection. In addition to HAART use, more immunogenic vaccines are likely needed for improving protection against influenza in this population.
[Show abstract][Hide abstract] ABSTRACT: Limited data exist on the immunogenicity of the 2009 influenza A (H1N1) vaccine among immunocompromised persons, including those with human immunodeficiency virus (HIV) infection.
We compared the immunogenicity and tolerability of a single dose of the monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009H1N1) between HIV-infected and HIV-uninfected adults 18-50 years of age. The primary end point was an antibody titer of ≥ 1:40 at day 28 after vaccination in those with a prevaccination level of ≤ 1:10, as measured by hemagglutination-inhibition assay. Geometric mean titers, influenza-like illnesses, and tolerability were also evaluated.
One hundred thirty-one participants were evaluated (65 HIV-infected and 66 HIV-uninfected patients), with a median age of 35 years (interquartile range, 27-42 years). HIV-infected persons had a median CD4 cell count of 581 cells/mm(3) (interquartile range, 476-814 cells/mm(3)) , and 82% were receiving antiretroviral medications. At baseline, 35 patients (27%) had antibody titers of >1:10. HIV-infected patients (29 [56%] of 52), compared with HIV-uninfected persons (35 [80%] of 44), were significantly less likely to develop an antibody response (odds ratio, .20; P = .003). Changes in the median geometric mean titer from baseline to day 28 were also significantly lower in HIV-infected patients than in HIV-uninfected persons (75 vs 153; P = .001). Five influenza-like illnesses occurred (2 cases in HIV-infected persons), but none was attributable to the 2009 influenza H1N1 virus. The vaccine was well tolerated in both groups.
Despite high CD4 cell counts and receipt of antiretroviral medications, HIV-infected adults generated significantly poorer antibody responses, compared with HIV-uninfected persons. Future studies evaluating a 2-dose series or more-immunogenic influenza A (H1N1) vaccines among HIV-infected adults are needed (ClinicalTrials.gov NCT00996970).
[Show abstract][Hide abstract] ABSTRACT: Erectile dysfunction (ED) and hypogonadism are increasingly recognized conditions, however, the prevalence and etiologies of these conditions among HIV-infected men remain unclear. We studied 300 HIV-infected men who completed standardized questionnaires regarding sexual function and hypogonadal symptoms. An early morning testosterone test was performed; patients with a low serum testosterone level (defined by <300 ng/dL), underwent additional blood tests to determine the etiology of the hypogonadism. The participants' mean age was 39 years (range, 19-72); 61% were Caucasian; 24%, African American; 9%, Hispanic; and 5% other. Participants had been HIV-positive for a mean of 9 years (range, 0.5-20) with a mean CD4 count of 522 cells/mm(3) (range, 1-1531). Sixty percent were receiving antiretroviral therapy. ED was reported by 61.4%; of those with ED, 32% did not have a rigid enough erection for penetration, and 46% were unable to sustain an erection for the completion of intercourse. In the multivariate analysis, increasing age (odds ratio [OR] 1.4 for a 5-year increment, p < 0.001) and depression (OR 2.64, p < 0.0001) were associated with ED. A higher current CD4 count was protective (OR 0.80 for each 100 cells/mm(3), p = 0.004). Only 25% of patients with ED had utilized a phosphodiesterase-5-inhibitor for treatment. Seventeen percent of the 300 men were hypogonadal; there was no correlation between hypogonadism and ED. Increasing age and a higher body mass index (BMI) were positively associated with hypogonadism, while smoking was negatively associated (OR 0.44, p = 0.02). All patients with low testosterone had secondary hypogonadism. There was no association between ED or hypogonadism with the current, past, or cumulative use of HIV medications.
AIDS PATIENT CARE and STDs 01/2007; 21(1):9-19. DOI:10.1089/apc.2006.0071 · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are increasingly described conditions in the general population, but there are currently no data regarding these conditions in HIV-infected persons without co-infection with hepatitis C virus. Methods: Clinic patients from a military HIV clinic with low rates of hepatitis C were prospectively enrolled to examine the prevalence and predictors of steatosis and abnormal liver function tests (LFTs) among HIV patients. A questionnaire regarding medication use and social/behavioral habits was performed along with a BMI assessment, LFTs, and liver ultrasound (US). Those with abnormal LFTs had a full laboratory panel to include iron studies, ceruloplasmin, autoimmunity panel, alpha-1 antitrypsin, and serum alcohol level to ascertain the etiology of the abnormality. A liver biopsy was performed for those with steatosis or liver disease of unclear etiology. Statistical analyses included Fishers exact and rank sum testing; multivariate models utilized backward stepwise logistic regression. Results: 60/200 (30%) had abnormal LFTs, most which were grade 1 (1.25-2.5x normal). The mean age of patients was 39 years (range, 20-68) with a mean CD4 count of 541 (18-1448 cells/mm3); 74% had received HAART. Of those with elevated LFTs, 7 (12%) were HbsAg positive, 2 (3%) hepatitis C seropositive, and one (2%) had probable hemochromatosis. In the multivariate model, past HAART use (OR 5.6, p=0.002), alcohol use (OR 1.1, p=0.01), and increased BMI (OR 1.1, p=0.03) were predictive of abnormal LFTs. Thirty percent (44/148) had steatosis on US; 41/44 (93%) met the criteria for NAFLD. Based on liver biopsy findings, US had a sensitivity of 83%, specificity of 90%, and PPV of 94% for detecting steatosis. 25% of patients had fibrosis on biopsy. Only 22% of those with steatosis had abnormal LFTs, but 90% had hepatomegaly. Predictors of steatosis in the multivariate model included BMI (OR 1.92 per 5 unit increase, p=0.01) with a trend towards d4T use (OR 1.7, p=0.13). BMI and waist circumference were correlated (r=0.73, p
[Show abstract][Hide abstract] ABSTRACT: Background: HIV-infected men have an increased rate of hypogonadism. There are no data regarding the rate of bone density abnormalities in this group. We evaluated prevalence and predictors of osteopenia/osteoporosis among hypogonadal men with HIV.
Methods: All adult HIV-infected men in our clinic (n=450) were offered study enrollment to evaluate for hypogonadism. Each participant had evaluation for early morning testosterone level. Those with hypogonadism were offered bone density testing with DEXA scans. Osteopenia was defined as a T-score -1 to -2.5 SD, and <-2.5 as osteoporosis. Statistical analysis included Fisher’s exact and rank sum tests. Multivariate logistic models were constructed.
Results: 300 patients were enrolled; the mean age of 39 years (range 19-72); 15% were greater than 50 years old. Mean duration of HIV was 9 years and mean CD4 count was 522 cells/mm3. Sixty percent were receiving antiretroviral therapy; 35% were on a protease inhibitor. Mean BMI was 26.7 (range 15.6-42.1). Fifty (17%) men were hypogonadal (<300 ng/dl) and 48 (16%) additional patients had borderline testosterone levels (300-400 ng/dl). Nineteen of the hypogonadal men had a DEXA scan; 48% had osteoporosis (32%) or osteopenia (16%). Those with osteopenia/osteoporosis had a lower estradiol level (36 vs. 60 pg/ml)) than those with normal bone density (p=0.03); there were no differences in demographics, CD4 counts, or ART/PI therapy.
Conclusion: Osteoporosis and osteopenia are common among HIV-infected men with hypogonadism with a prevalence rate of 50% in our small sample. Low estrogen levels, along with low testosterone levels, are associated with a low bone density as measured by DEXA in this population. HIV-positive patients diagnosed with hypogonadism should be concurrently screened for osteoporosis.
Infectious Diseases Society of America 2006 Annual Meeting; 10/2006
[Show abstract][Hide abstract] ABSTRACT: Background: HSV2 influences both HIV transmission and acquisition, but its affect on HIV progression is unclear. We evaluated the impact of HSV2 on HIV progression in a large HIV cohort.
Methods: HIV-infected persons were tested for HSV2 using a type specific serologic assay. Demographics, hepatitis serologies, time to antiretroviral medications (CD4 count <350 or 18%), CD4 counts and HIV viral loads (VLs) for 3 years were collected. HIV seroconverters were defined by a negative HIV test within two years of their first positive test. HSV2 seropositive patients were compared to seronegative patients using Fisher’s exact and rank sum tests. Differences in the rate of CD4 and VL changes over time were analyzed.
Results: 200 (55%) of 367 HIV patients were HSV2 seropositive. Those with HSV2 were older (p<0.001) and hepatitis B core antibody positive (p=0.004) compared to HSV2 negatives. The baseline CD4 count was not significantly different between those with and without HSV2. However, HSV2 seropositive compared to seronegative patients had a greater decline in CD4 counts from baseline to 1 year (130 CD4 cell difference, p=0.003) and at 3 years (142 CD4 cell difference, p=0.03). VL’s showed a nonsignificant trend toward higher values (0.1 log increase at 1 year, and 0.6 at 3 years) among those with HSV2. 219 (60%) patients were documented HIV seroconverters; similar CD4 and VL changes were noted in this group. The percentage of HSV2 patients requiring HIV medications at <1 year or at 3 years after HIV diagnosis was not significantly different from those without HSV2.
Conclusion: HSV2 co-infection results in a greater decline in the CD4 counts during early HIV infection. The clinical significance of this findings is unclear, since the time to initiating ART was not significantly altered.
Infectious Diseases Society of America 2006 Annual Meeting; 10/2006
[Show abstract][Hide abstract] ABSTRACT: Background: As HIV-infected patients live longer and may be exposed to potentially nephrotoxic medications, there may be an increasing likelihood of renal dysfunction. We evaluated the prevalence and predictors of renal dysfunction among HIV patients.
Methods: We reviewed creatinine values of 303 HIV patients with >38,200 months of follow-up. Creatinine clearance (CrCl) using the Cockroft-Gault formula and MDRD were calculated. CrCl values were compared using T tests; predictors for declining renal function were analyzed using linear regression models.
Results: The 303 patients had a mean age of 40.1 years (range 20-70) and a mean duration of HIV of 10.5 years. HIV patients’ mean current CrCl (107.3 ml/min) was lower than the baseline CrCl at time of HIV diagnosis (112.3) (p=0.001), but consistent with the reduction in CrCl in the general population with aging. Predictors of a greater decline in CrCl included increasing age (p=0.002), race (p=0.044), hypertension (p=0.007), and tenofovir use (p=0.009). Years of HIV infection was not predictive. In the multivariate analysis, race, hypertension and tenofovir remained significant. We evaluated CrCl values before and after 2 years of HAART and there were no significant changes (112.7 vs. 112.9 ml/min). There was a significant decline in the CrCl of -9.3 ml/min (112.3 vs. 103.0, p<0.001) during a mean of 2 years of tenofovir use with 16% of patients developing a CrCl<80ml/min and 72% loosing some renal function with tenofovir treatment.
Conclusion: Creatinine clearance decreased in HIV patients at a similar rate compared to the general population suggesting that HIV does not significantly increase the rate of renal dysfunction. Modifiable predictors of a greater decline in renal function among HIV patients include hypertension and tenofovir use.
Infectious Diseases Society of America 2006 Annual Meeting; 10/2006
[Show abstract][Hide abstract] ABSTRACT: Hepatitis A is a major health risk for many human immunodeficiency virus (HIV)-infected individuals. Vaccination is a potentially attractive measure to reduce the incidence of hepatitis A among this population, but data on its safety and immunogenicity are incomplete.
Ninety HIV-uninfected adults received an inactivated hepatitis A vaccine (VAQTA; Merck), and 90 HIV-infected subjects were randomized, in double-blind fashion, to receive either the vaccine or placebo. The HIV-infected subjects were stratified by CD4 cell count, with 45 subjects having CD4 cell counts of > or =300 cells/mm3 and 45 subjects having CD4 cell counts of <300 cells/mm3. Vaccine was given at weeks 0 and 24 of the study.Results. Seroconversion rates at week 28 of the study were 94% among the HIV-infected subjects and 100% among the HIV-uninfected control subjects. HIV-infected subjects with CD4 cell counts of <300 cells/mm3 had a seroconversion rate of 87%, and HIV-infected subjects with CD4 cell counts of > or =300 cells/mm3 had a seroconversion rate of 100%. The vaccine was generally well tolerated, and no adverse effect on either HIV load or CD4 cell count was found.
Hepatitis A vaccine was both immunogenic and safe among HIV-infected subjects.
[Show abstract][Hide abstract] ABSTRACT: The immunologic correlates associated with control of viremia in HIV disease are poorly understood. We hypothesized that structured antiviral drug treatment interruptions could be utilized to better understand the relationship between HIV-specific immunity and viral replication. We thus examined the effects of two 8 weeks antiviral structured treatment interruptions (STIs) in a cohort of HIV-1 chronically infected individuals on highly active antiretroviral treatment (HAART) with (n = 13) and without (n = 12) therapeutic HIV immunizations. In this study, we observed that p24 gag antigen (np24) stimulated MIP-1beta levels and T helper immune responses prior to antiviral drug discontinuation were associated with control of viremia. Stronger and earlier production of gag peptide stimulated gamma interferon was observed in the immunized group during the structured antiviral drug interruptions. These results support the concept that HIV-specific immune responses are associated with control of viremia. Further study of immune-based therapies that enhance HIV-specific immunity is warranted.