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1.  Predictors of the Isolated Hepatitis B Core Antibody Pattern in HIV-Infected and -Uninfected Men in the Multicenter AIDS Cohort Study 
The isolated hepatitis B core antibody (anti-HBc) pattern was generally stable, associated with human immunodeficiency virus and hepatitis C virus infection, and most commonly transitioned to or from a pattern of past infection. The isolated anti-HBc pattern likely represents resolved hepatitis B virus infection with low or undetected anti-HBs.
Background. The significance of hepatitis B core antibody (anti-HBc) without hepatitis B surface antigen (HBsAg) or hepatitis B surface antibody (anti-HBs) is unclear.
Methods. This cohort study included men enrolled in the Multicenter AIDS Cohort to determine clinical and laboratory predictors of isolated anti-HBc.
Results. A total of 2286 subjects (51% human immunodeficiency virus [HIV]–infected) were followed over 3.9 years. Overall, 16.9% (387) had at least 1 visit with isolated anti-HBc. The isolated anti-HBc pattern was stable 84% of the time, and transitioned to or from a pattern of past infection (anti-HBc and anti-HBs). Isolated anti-HBc was associated with HIV infection (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.73–2.79) and hepatitis C virus (HCV; OR, 4.21; 95% CI; 2.99–5.91). The HCV association was stronger for chronic HCV infection (OR, 6.76; 95% CI, 5.08–8.99) than for cleared HCV (OR, 3.03; 95% CI, 1.83–5.03). HIV infection, chronic HCV, and cleared HCV infection all remained associated with isolated anti-HBc in multivariable models (OR, 1.74; 95% CI, 1.33–2.29; OR, 6.24; 95% CI, 4.62–8.42; and OR, 2.77; 95% CI, 1.65–4.66, respectively). Among HIV-infected subjects, highly active antiretroviral therapy was negatively associated (OR, 0.79; 95% CI, .66–.95) with isolated anti-HBc.
Conclusions. Isolated anti-HBc is associated with HIV and HCV coinfection, especially active HCV replication, and most commonly occurs as a transition to or from the pattern of natural immunity (anti-HBc and anti-HBs). The isolated anti-HBc pattern likely represents resolved HBV infection with low or undetected anti-HBs.
PMCID: PMC3552525  PMID: 23090927
hepatitis B core antibody; human immunodeficiency virus; hepatitis C; highly active antiretroviral therapy
2.  Acute HIV-1 Seroconversion with an Unusual Plasma Biomarker Profile 
Clinical and Vaccine Immunology : CVI  2013;20(11):1774-1777.
An unusual case of acute primary HIV-1 infection in a man with a high plasma viral load, a 51-fold increase in C-reactive protein, and antibodies against only gp160 is described. Numerous serum cytokine concentrations were elevated during HIV-1 seroconversion.
PMCID: PMC3837784  PMID: 24006141
3.  Lower Adiponectin is Associated with Subclinical Cardiovascular Disease among HIV-infected Men 
AIDS (London, England)  2014;28(6):901-909.
To examine if altered levels of adipokines, adipose-derived peptides associated with myocardial infarction in the general population, may contribute to subclinical coronary atherosclerosis in HIV-infected persons.
Nested cohort study.
We studied HIV-infected(HIV+) and HIV-uninfected(HIV−) men in the Multicenter AIDS Cohort Study with noncontrast CT to measure coronary artery calcium and regional adiposity; 75% additionally underwent coronary CT angiography to measure plaque composition and stenosis. Adiponectin and leptin levels were assessed. Multiple regression models were used to assess associations between adipokine levels and HIV disease parameters, regional adiposity, and plaque adjusted for age, race, HIV serostatus and CVD risk factors (RFs).
Significant findings were limited to adiponectin. HIV+ men (n=493) had lower adiponectin levels than HIV− men (n=250) after adjusting for CVD RFs (p<0.0001), which became non-significant after adjustment for abdominal visceral and thigh subcutaneous adipose tissue. Among HIV+ men, lower adiponectin levels were associated with higher CD4+ T cell counts (p= 0.004), longer duration of antiretroviral therapy (p= 0.006) and undetectable HIV RNA levels (p = 0.04) after adjusting for age, race and CVD RFs; only CD4+ cell count remained significant after further adjustment for adipose tissue. In both groups, lower adiponectin levels were associated with increased odds of coronary stenosis > 50% (p <0.007). Lower adiponectin levels were associated with increased extent of plaque in HIV+ and of mixed plaque in HIV− men.
Adiponectin levels were lower in HIV-infected men and related to the severity of subclinical atherosclerosis, independent of traditional CVD risk factors.
PMCID: PMC3967406  PMID: 24401646
Adipokines; adiponectin; leptin; heart; subclinical coronary atherosclerosis; metabolic side effects of HIV infection; coronary CT angiography; cardiac CT
4.  Readmissions at a Public Safety Net Hospital 
PLoS ONE  2014;9(3):e91244.
We aimed to determine factors related to avoidability of 30-day readmissions at our public, safety net hospital in the United States (US).
We prospectively reviewed medical records of adult internal medicine patients with scheduled and unscheduled 30-day readmissions. We also interviewed patients if they were available. An independent panel used pre-specified, objective criteria to adjudicate potential avoidability.
Of 153 readmissions evaluated, 68% were unscheduled. Among these, 67% were unavoidable, primarily due to disease progression and development of new diagnoses. Scheduled readmissions accounted for 32% of readmissions and most (69%) were clinically appropriate and unavoidable. The scheduled but avoidable readmissions (31%) were attributed largely to limited resources in our healthcare system.
Most readmissions at our public, safety net hospital were unavoidable, even among our unscheduled readmissions. Surprisingly, one-third of our overall readmissions were scheduled, the majority reflecting appropriate management strategies designed to reduce unnecessary hospital days. The scheduled but avoidable readmissions were due to constrained access to non-emergent, expensive procedures that are typically not reimbursed given our system’s payor mix, a problem which likely plague other safety net systems. These findings suggest that readmissions do not necessarily reflect inadequate medical care, may reflect resource constraints that are unlikely to be addressable in systems caring for a large burden of uninsured patients, and merit individualized review.
PMCID: PMC3949745  PMID: 24618829
5.  Factors Affecting Glomerular Filtration Rate, as Measured by Iohexol Disappearance, in Men with or at Risk for HIV Infection 
PLoS ONE  2014;9(2):e86311.
Formulae used to estimate glomerular filtration rate (GFR) underestimate higher GFRs and have not been well-studied in HIV-infected (HIV(+)) people; we evaluated the relationships of HIV infection and known or potential risk factors for kidney disease with directly measured GFR and the presence of chronic kidney disease (CKD).
Cross-sectional measurement of iohexol-based GFR (iGFR) in HIV(+) men (n = 455) receiving antiretroviral therapy, and HIV-uninfected (HIV(−)) men (n = 258) in the Multicenter AIDS Cohort Study.
iGFR was calculated from disappearance of infused iohexol from plasma. Determinants of GFR and the presence of CKD were compared using iGFR and GFR estimated by the CKD-Epi equation (eGFR).
Median iGFR was higher among HIV(+) than HIV(−) men (109 vs. 106 ml/min/1.73 m2, respectively, p = .046), and was 7 ml/min higher than median eGFR. Mean iGFR was lower in men who were older, had chronic hepatitis C virus (HCV) infection, or had a history of AIDS. Low iGFR (≤90 ml/min/1.73 m2) was associated with these factors and with black race. Other than age, factors associated with low iGFR were not observed with low eGFR. CKD was more common in HIV(+) than HIV(−) men; predictors of CKD were similar using iGFR and eGFR.
iGFR was higher than eGFR in this population of HIV-infected and -uninfected men who have sex with men. Presence of CKD was predicted equally well by iGFR and eGFR, but associations of chronic HCV infection and history of clinically-defined AIDS with mildly decreased GFR were seen only with iGFR.
PMCID: PMC3917840  PMID: 24516530
6.  Morning free and total testosterone in HIV-infected men: implications for the assessment of hypogonadism 
Hypogonadism is common among HIV-infected men, even among men receiving antiretroviral therapy (ART). Our objective in this study was to determine the prevalence of biochemical hypogonadism among HIV-infected men compared with HIV-uninfected controls. We also examined the use of free testosterone (FT) and total testosterone (TT) measurements in the assessment of biochemical hypogonadism in HIV-infected and –uninfected men.
This was a cross-sectional analysis from the Multicenter AIDS Cohort Study (MACS). TT levels were measured from archived serum using liquid chromatography-tandem mass spectrometry. FT was calculated from TT and sex hormone-binding globulin (SHBG) (measured by radioimmunoassay) using the Vermeulen equation. Biochemical hypogonadism was defined as having low TT, low FT, or both.
Of 945 men in the MACS Cardiovascular Substudy, T assays were not performed in 89 because of insufficient/no stored serum (n = 18) or use of T replacement therapy (TRT) (n = 71). 530 men had morning (AM) T measurements; 364 (68.7%) were HIV-infected. The prevalence of biochemical hypogonadism was similar in HIV-infected (34/364 = 9.3%) and HIV-uninfected (12/166 = 7.2%) men. Prevalence of hypogonadism, when men on TRT (n = 71) were included in the group of hypogonadal men, was higher in HIV-infected (104/434 = 24.0%) compared with HIV-uninfected (13/167 = 7.8%) men (p < 0.0001). Of 34 HIV-infected men with biochemical hypogonadism not on TRT, 11 (32.4%) had normal TT, but low FT. Of 12 HIV-uninfected men with biochemical hypogonadism not on TRT, none were in this category (p = 0.04) – all had low TT.
The prevalence of biochemical hypogonadism in our sample of HIV-infected men was approximately 10%, with a substantial proportion of these men having a normal TT, but low FT. The measurement of AM FT, rather than TT, in the assessment of hypogonadism in HIV-infected men will likely increase diagnostic sensitivity and should be recommended.
PMCID: PMC3900935  PMID: 24450960
Testosterone; Sex hormone binding globulin; HIV; Hypogonadism
7.  The Impact of Impaired Kidney Function and HIV Infection on the Risk of Anemia 
AIDS Research and Human Retroviruses  2012;28(12):1666-1671.
Chronic kidney disease and HIV infection both independently increase the risk of anemia. It is not known if individuals with both HIV infection and kidney dysfunction are at greater than expected risk of anemia resulting from the combined effect of these factors. Men from the Multicenter AIDS Cohort Study with AIDS-free time after 1996 were included in the analysis if they had an initial hemoglobin value greater than 13 g/dl and available serum creatinine measurements for the estimation of glomerular filtration rate. Hemoglobin data were fit parametrically using a linear mixed effects model and effects of medication use on hemoglobin levels were removed using censoring methods. The effect of both HIV infection and glomerular filtration rate less than 60 ml/min/1.73 m2 on the mean hemoglobin value was assessed. The risk of having anemia (hemoglobin level falling below 13 g/dl) was estimated. There were 862 HIV-infected and 1,214 HIV-uninfected men who contributed to the analysis. Hemoglobin values across all 17,341 person-visits, adjusting for age, were generally lower in HIV-infected AIDS-free men with impaired kidney function by −0.22 g/dl (95% CI: −0.42, −0.03) compared to men with either HIV infection or impaired kidney function, but not both. HIV-infected AIDS-free men with impaired kidney function have a higher risk of anemia by 1.2% compared to HIV-uninfected men with normal kidney function. Comorbid conditions and medication use did not explain this increase in risk. HIV infection and impaired kidney function have a combined impact on lowering hemoglobin levels, resulting in a higher risk of anemia.
PMCID: PMC3505063  PMID: 22632256
8.  Use of Cardiac CT Angiography Imaging in an Epidemiology Study – the Methodology of the Multicenter AIDS Cohort Study Cardiovascular Disease Substudy 
The methodology for use of cardiac CT angiography (CTA) in low risk populations is not well defined. In order to present a reference for future studies, we present CTA methodology that is being used in an epidemiology study- the Multicenter AIDS Cohort Study (MACS).
The Multicenter AIDS Cohort Study (MACS) is an on-going multicenter prospective, observational cohort study. The MACS Cardiovascular Disease substudy plans to enroll 800 men (n= 575 HIV seropositive and n= 225 HIV seronegative) age 40-75 years for coronary atherosclerosis imaging using cardiac CTA. The protocol includes heart rate (HR) optimization with beta blockers; use of proper field of view; scan length limitation; prospective ECG-gating using the lowest beam voltage possible. All scans are evaluated for presence, extent, and composition of coronary atherosclerosis, left atrial volumes, left ventricular volume and mass and non-coronary cardiac pathology.
The first 498 participants had an average radiation dose of 2.5±1.6 milliSieverts (mSv) for the cardiac CTA study. Overall quality of scans was fair to excellent in 98.6% of studies. There were three significant adverse events- two allergic reactions to contrast and one subcutaneous contrast extravasation.
Cardiac CTA was safe and afforded a low effective radiation exposure to these asymptomatic research participants and provides valuable cardiovascular endpoints for scientific analysis. The cardiac CTA methodology described here may serve as a reference for use in future epidemiology studies aiming to assess coronary atherosclerosis and cardiac anatomy in low risk populations while minimizing radiation exposure.
PMCID: PMC3673004  PMID: 23376648
CT angiography; radiation dose; epidemiological study
9.  Subclinical coronary atherosclerosis, HIV infection and antiretroviral therapy: Multicenter AIDS Cohort Study 
AIDS (London, England)  2008;22(13):1589-1599.
To evaluate the association of HIV infection and cumulative exposure to highly active antiretroviral therapy (HAART) with the presence and extent of coronary artery calcification (CAC).
A cross-sectional study of 947 male participants (332 HIV-seronegative, 84 HAART-naive and 531 HAART-experienced HIV-infected) from the Multicenter AIDS Cohort Study.
The main outcome was CAC score calculated as the geometric mean of the Agatston scores of two computed tomography replicates. Presence of CAC was defined as calcification score above 10, and extent of CAC by the score for those with CAC present. Multivariable regression was used to evaluate the association between HIV infection and HAART and presence and extent of calcification.
Increasing age was most strongly associated with both prevalence and extent of CAC for all study groups. After adjustment for age, race, family history, smoking, high-density lipoprotein-C, low-density lipoprotein-C and hypertension, HIV infection (odds ratio, 1.35; 95% confidence interval, 0.70, 2.61) and long-term HAART use (odds ratio, 1.33; 95% confidence interval, 0.87, 2.05) increased the odds for presence of CAC. In contrast, after adjustment for these covariates, the extent of CAC was lower among HAART users. Among those not taking lipid-lowering therapy, HAART usage of at least 8 years was associated with significantly reduced CAC scores (relative CAC score, 0.43; 95% confidence interval, 0.24, 0.79).
HAART use may have different effects on the presence and extent of coronary calcification. Although prevalence of calcification was marginally increased among long-term HAART users, the extent of calcification was significantly reduced among HAART users compared with HIV-seronegative controls.
PMCID: PMC3633463  PMID: 18670218
10.  HIV Monoinfection Is Associated With Increased Aspartate Aminotransferase-to-Platelet Ratio Index, a Surrogate Marker for Hepatic Fibrosis 
The Journal of Infectious Diseases  2012;205(6):1005-1013.
Background. Although liver disease commonly causes morbidity and mortality among human immunodeficiency virus (HIV)–infected individuals, data are limited on its prevalence in HIV monoinfection. We used the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate marker of hepatic fibrosis to characterize liver disease in the Multicenter AIDS Cohort Study.
Methods. Men were categorized based on their HIV and viral hepatitis status: uninfected (n = 1170), HIV monoinfected (n = 509), viral hepatitis monoinfected (n = 74), and HIV–viral hepatitis coinfected (n = 66).
Results. The median APRI in the HIV-monoinfected group was similar to that in the hepatitis-monoinfected group (0.42 vs 0.43; P > .05), higher than in the uninfected group (0.42 vs 0.27; P < .001) but lower than in the coinfected group (0.42 vs 1.0; P < .001). On multivariable analysis, HIV infection (1.39-fold increase [FI]; P < .001), viral hepatitis infection (1.52-FI; P < .001), and the interaction between HIV and viral hepatitis infections were independently associated with a higher APRI (1.57-FI; P < .001). Among the HIV-infected men, viral hepatitis coinfection (2.34-FI; P < .001), HIV RNA ≥100 000 copies/mL (1.26-FI; P = .007), and CD4 count ≤200 cells/mL (1.23-FI; P = .022) were independently associated with a higher APRI.
Conclusions. HIV and viral hepatitis are independently associated with an increased APRI. Further studies are needed to understand the biological basis for the association between HIV and liver disease.
PMCID: PMC3282573  PMID: 22291196
11.  Sex Hormones, Insulin Resistance, and Diabetes Mellitus among Men with or at Risk for HIV Infection 
To examine the relationship of free testosterone (FT) and sex hormone-binding globulin (SHBG) with insulin resistance and diabetes mellitus (DM) in HIV disease.
Cross-sectional analysis from 322 HIV-uninfected and 534 HIV-infected men in the Multicenter AIDS Cohort Study.
The main outcomes were DM and Homeostasis model assessment–insulin resistance (HOMA-IR). DM was defined as fasting serum glucose (FG) ≥ 126 or self-reported DM and use of DM medications. Homeostasis model assessment–insulin resistance (HOMA-IR) was calculated from FG and fasting insulin.
Compared with HIV-uninfected men in our sample, HIV-infected men were younger, with lower BMI, and more often black. HIV-infected men had lower FT (p < 0.001) and higher SHBG (p < 0.0001). The adjusted odds ratio for DM was 1.98 (95% CI 1.04–3.78); mean adjusted log HOMA-IR was 0.21 units higher in HIV-infected men (p < 0.0001). Log SHBG, but not log FT, was associated with DM (OR = 0.44, 95% CI 0.25, 0.80) in both groups. Log FT and log SHBG were inversely related to insulin resistance (p < 0.05 for both) independent of HIV.
Compared to HIV-uninfected men, HIV-infected men had lower FT, higher SHBG, and more insulin resistance and DM. Lower FT and lower SHBG were associated with insulin resistance regardless of HIV serostatus. This suggests that sex hormones play a role in the pathogenesis of glucose abnormalities among HIV-infected men.
PMCID: PMC3175332  PMID: 21705912
Testosterone; Sex Hormone-Binding Globulin; Insulin Resistance; Diabetes Mellitus; HIV
12.  Serologic responses to Pneumocystis Proteins in Human Immunodeficiency Virus Patients With and Without Pneumocystis jirovecii Pneumonia 
Immune responses to Pneumocystis jirovecii are not well understood in HIV infection, but antibody responses to proteins may be useful as a marker of Pneumocystis risk or presence of Pneumocystis pneumonia (PcP).
Retrospective analysis of a prospective cohort
Enzyme-linked immunosorbent assays of antibodies to recombinant Pneumocystis proteins of major surface glycoprotein fragments (MsgC1, C3, C8, and C9) and of antibody titers to recombinant kexin protein (KEX1) were performed on three sequential serum samples up to 18 months prior to and three samples after first AIDS-defining illness from Multicenter AIDS Cohort Study participants and compared between those who had PcP or a non-PcP AIDS-defining illness.
Fifty-four participants had PcP and 47 had a non-PcP AIDS-defining illness. IgG levels to MsgC fragments were similar between groups prior to first AIDS-defining illness, but the PcP group had higher levels of IgG to MsgC9 (median units/ml 50.2 vs. 22.2, p=0.047) post-illness. Participants with PcP were more likely to have an increase in MsgC3 (OR 3.9, p=0.02), MsgC8 (OR 5.5, p=0.001), and MsgC9 (OR 4.0, p=0.007). The PcP group was more likely to have low KEX1 IgG prior to development of PcP (OR 3.6, p=0.048) independent of CD4 cell count and to have an increase in high IgG titers to KEX1 after PcP.
HIV-infected individuals develop immune responses to both Msg and kexin proteins after PcP. Low KEX1 IgG titers may be a novel marker of future PcP risk before CD4 cell count has declined below 200 cells/μl.
PMCID: PMC3150634  PMID: 21372726
HIV; Acquired Immunodeficiency Syndrome; Pneumocystis; serology
13.  A Controlled Investigation of Optimal Internal Medicine Ward Team Structure at a Teaching Hospital 
PLoS ONE  2012;7(4):e35576.
The optimal structure of an internal medicine ward team at a teaching hospital is unknown. We hypothesized that increasing the ratio of attendings to housestaff would result in an enhanced perceived educational experience for residents.
Harbor-UCLA Medical Center (HUMC) is a tertiary care, public hospital in Los Angeles County. Standard ward teams at HUMC, with a housestaff∶attending ratio of 5∶1, were split by adding one attending and then dividing the teams into two experimental teams containing ratios of 3∶1 and 2∶1. Web-based Likert satisfaction surveys were completed by housestaff and attending physicians on the experimental and control teams at the end of their rotations, and objective healthcare outcomes (e.g., length of stay, hospital readmission, mortality) were compared.
Nine hundred and ninety patients were admitted to the standard control teams and 184 were admitted to the experimental teams (81 to the one-intern team and 103 to the two-intern team). Patients admitted to the experimental and control teams had similar age and disease severity. Residents and attending physicians consistently indicated that the quality of the educational experience, time spent teaching, time devoted to patient care, and quality of life were superior on the experimental teams. Objective healthcare outcomes did not differ between experimental and control teams.
Altering internal medicine ward team structure to reduce the ratio of housestaff to attending physicians improved the perceived educational experience without altering objective healthcare outcomes.
PMCID: PMC3330818  PMID: 22532860
14.  Hepatitis B and long-term HIV outcomes in co-infected HAART recipients 
AIDS (London, England)  2009;23(14):1881-1889.
Chronic hepatitis B (CH-B) is common among HIV-infected individuals and increases liver-related mortality in the absence of highly active antiretroviral therapy (HAART). The impact of CH-B on long-term HAART outcomes has not been fully characterized.
To address this question, HAART initiators enrolled in the Multicenter AIDS Cohort Study (MACS) were retrospectively analyzed. Subjects were classified by hepatitis B category based on serology at the time of HAART initiation. The association of CH-B with mortality, AIDS defining illnesses, CD4 rise, and HIV suppression was assessed using regression analysis.
Of 816 men followed for a median of 7 years on HAART, 350 were never HBV infected, 357 had past infection, 45 had CH-B, and 64 were only core-antibody positive. Despite HAART, AIDS-related mortality was the most common cause of death (8.3/1000 person-years (PYs)). It was highest in those with CH-B (17/1000 PYs, 95% CI 7.3, 42) and lowest among never HBV infected (2.9/1000 PYs, 95% CI 1.4, 6.4). In a multivariable model, patients with CH-B had a 2.7-fold higher incidence of AIDS-related mortality compared to those never infected (P=0.08). Non-AIDS-related mortality was also highest among those with CH-B (22/1000 PYs), primarily due to liver disease (compared to never infected, adjusted HR 4.1, p=0.04). There was no significant difference in AIDS defining events, HIV RNA suppression, and CD4 increase.
In HIV-infected patients receiving long-term HAART, HBV status did not influence HIV suppression or CD4 increase. However, mortality was highest among those with CH-B and was mostly due to liver disease despite HBV-active HAART.
PMCID: PMC2861825  PMID: 19550291
hepatitis B; HIV; HAART; CD4; mortality; isolated core hepatitis B
15.  Interaction between RANTES promoter variant and CCR5Δ32 favors recovery from hepatitis B 
Recovery from acute hepatitis B virus (HBV) infection occurs in 95% of adult-acquired infections. A 32-base pair deletion in CCR5 (CCR5Δ32), which encodes for a nonfunctional receptor, increases the likelihood of recovery. Using 181 subjects with persistent HBV infection and 316 who had recovered, we tested the hypothesis that an epistatic interaction between functional polymorphisms in RANTES (a CCR5 ligand) and CCR5 impacts recovery. Specific models designed to assess individual contributions of compound genotypes demonstrated that the only combination associated with recovery from an HBV infection was RANTES -403A with CCR5Δ32 (OR 0.36, P= 0.02). Since the phenotypic consequence of -403A is reported to be higher levels of RANTES, we propose a model where excess RANTES in combination with low CCR5 favor recovery from an HBV infection, which will require validation through functional testing. “This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third party. The final, citable version of record can be found at”
PMCID: PMC2650505  PMID: 19017985
Viral infection; chemokines; human
16.  Sexual activity and Kaposi’s sarcoma among HIV-1 and HHV-8 coinfected men 
Annals of epidemiology  2008;18(7):517-521.
There is notable heterogeneity in the progression to Kaposi’s Sarcoma (KS) among men coinfected with HIV-1 and HHV-8; additional determinants of KS likely exist. Here, we explore sexual activity as a proxy for a sexually transmitted determinant beyond HIV-1 and HHV-8.
The association between sexual activity and incident KS was estimated using data from 1,354 HIV-1 and HHV-8 coinfected homosexual men followed for up to 10 years in the Multicenter AIDS Cohort Study.
As expected, white race, low CD4 cell count and acquiring HHV-8 after HIV-1 infection increased, while smoking decreased, the hazard of KS. The unadjusted hazard of KS among those with high sexual activity was 0.68 relative to the hazard of those with low sexual activity (95% confidence interval [CI]: 0.49, 0.93), and was somewhat muted after adjustment for characteristics measured at study entry (i.e. race, smoking, CD4 cell count, infection order, history of sexual activity, and sexually transmitted diseases). However, adjustment for time-varying covariates, particularly CD4 cell count, resulted in a nullification of the association (adjusted hazard ratio = 1.06; 95% CI: 0.77, 1.48).
Once HIV-1 and HHV-8 coinfection is established in homosexual men, progression to KS does not appear to be due to a third pathogen transmitted by sexual activity.
PMCID: PMC2587441  PMID: 18504143
HIV-1; HHV-8; Kaposi’s sarcoma; sexual activity
17.  Fat distribution and longitudinal anthropometric changes in HIV-infected men with and without clinical evidence of lipodystrophy and HIV-uninfected controls: A substudy of the Multicenter AIDS Cohort Study 
Fat abnormalities are common among HIV-infected persons, but few studies have compared regional body fat distribution, including visceral fat, in HIV-infected and HIV-uninfected persons and their subsequent trajectories in body composition over time.
Between 1999 and 2002, 33 men with clinical evidence of lipodystrophy (LIPO+), 23 HIV-infected men without clinical evidence of lipodytrophy (LIPO-), and 33 HIV-uninfected men were recruited from the four sites of the Multicenter AIDS Cohort Study (MACS). Participants underwent dual-energy x-ray absorptiometry, quantitative computerized tomography of the abdomen and thigh, and circumference measurements of the waist, hip and thigh. Circumference measurements at each semi-annual MACS visit between recruitment and 2008 were used to compare average annual anthropometric changes in the 3 groups.
Body mass index (BMI) was lower in LIPO+ men than in the LIPO- men and the HIV- uninfected controls (BMI: 23.6 ± 0.4 vs 26.8 ± 1.5 vs 28.7 ± 0.9 kg/m2, respectively, p < 0.001). The average amount of visceral adipose tissue (VAT) was similar in all three groups (p = 0.26), but after adjustment for BMI, VAT was higher in the LIPO+ group (169 ± 10 cm2) compared to the LIPO- men (129 ± 12 cm2, p = 0.03) and the HIV-uninfected group (133 ± 11 cm2, p = 0.07). Subcutaneous adipose tissue (thigh, abdomen) and total extremity fat were less in the HIV-infected men (LIPO+ and LIPO-) than in the HIV-uninfected men. Over an average of 6 years of follow-up, waist circumference increased at a faster rate in LIPO+ group, compared to the LIPO- men (0.51 cm/year vs 0.08 cm/year, p = 0.02) and HIV-uninfected control men (0.21 cm/year, p = 0.06). The annual changes in hip and thigh circumferences were similar in all three groups
Subcutaneous lipoatrophy was observed in HIV-infected patients, even those without clinical evidence of lipodystrophy, compared to age-matched HIV-uninfected men. Despite markedly lower BMI, HIV-infected men with lipodystrophy had a similar amount of VAT as HIV-uninfected men and tended to have more rapid increases in waist circumference over 6 years of follow-up. These longitudinal increases in waist circumference may contribute to the development of cardiovascular risk in HIV-infected patients with lipodystrophy.
PMCID: PMC2686733  PMID: 19439092
18.  Genetic Protection against Hepatitis B Virus Conferred by CCR5Δ32: Evidence that CCR5 Contributes to Viral Persistence▿  
Journal of Virology  2006;81(2):441-445.
Recovery from acute hepatitis B virus (HBV) infection requires a broad, vigorous T-cell response, which is enhanced in mice when chemokine receptor 5 (CCR5) is missing. To test the hypothesis that production of a nonfunctional CCR5 (CCR5Δ32 [a functionally null allele containing a 32-bp deletion]) increases the likelihood of recovery from hepatitis B in humans, we studied 526 persons from three cohorts in which one person with HBV persistence was matched to two persons who recovered from an HBV infection. Recovery or persistence was determined prior to availability of lamivudine. We determined genotypes for CCR5Δ32 and for polymorphisms in the CCR5 promoter and in coding regions of the neighboring genes, chemokine receptor 2 (CCR2) and chemokine receptor-like 2 (CCRL2). Allele and haplotype frequencies were compared among the 190 persons with viral recovery and the 336 with persistence by use of conditional logistic regression. CCR5Δ32 reduced the risk of developing a persistent HBV infection by nearly half (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33 to 0.83; P = 0.006). This association was virtually identical in persons with and without a concomitant human immunodeficiency virus infection. Of the nine individuals who were homozygous for the deletion, eight recovered from infection (OR, 0.25; 95% CI, 0.03 to 1.99; P = 0.19). None of the other neighboring polymorphisms examined were associated with HBV outcome. These data demonstrate a protective effect of CCR5Δ32 in recovery from an HBV infection, provide genetic epidemiological evidence for a role of CCR5 in the immune response to HBV, and suggest a potential therapeutic treatment for patients persistently infected with HBV.
PMCID: PMC1797425  PMID: 17079285

Results 1-18 (18)