Publications by authors named "Mollie Roediger"

28 Publications

  • Page 1 of 1

Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy: Findings from the START Bone Mineral Density Substudy, a Randomized Trial.

J Bone Miner Res 2017 Sep 26;32(9):1945-1955. Epub 2017 Jun 26.

St Vincent's Hospital, Sydney, Australia.

Both HIV infection and antiretroviral therapy (ART) are associated with lower bone mineral density (BMD) and increased fracture risk. Because the relative contributions of ART and untreated HIV to BMD loss are unclear, it is important to quantify the effect of ART on bone. We compared the effect of early ART initiation (CD4 >500 cells/μL) with deferred ART on change in BMD in the START Bone Mineral Density substudy, a randomized trial evaluating the effect of immediate ART initiation versus deferring ART (to CD4 <350 cells/μL). BMD was measured annually at the lumbar spine and hip by dual-energy X-ray absorptiometry (DXA). Percent change in BMD by treatment assignment (intent-to-treat analysis) was estimated using longitudinal mixed models and linear regression. Baseline and follow-up DXA scans were available for 399 (195 immediate, 204 deferred) participants (median age 32 years, 80% non-white, 26% women, median CD4 count 642 cells/μL). ART (most commonly including tenofovir and efavirenz) was used for 95% and 18% of follow-up in the immediate and deferred ART groups, respectively. Through 2.2 years mean follow-up, immediate ART resulted in greater BMD declines than deferred ART at the hip (-2.5% versus -1.0%; difference -1.5%, 95% confidence interval [CI] -2.2 to -0.8, p < 0.001) and spine (-1.9% versus -0.4%; difference -1.6%, 95% CI -2.2 to -1.0, p < 0.001). BMD declines were greatest in the first year of ART. In the immediate ART group, spine BMD stabilized after year 1, whereas hip BMD declined progressively over 2 years. After year 1, BMD changes were similar in the immediate and deferred groups. No clinical, HIV-related, or ART characteristic predicted greater BMD loss in either group. All HIV treatment guidelines now recommend ART initiation at HIV diagnosis because of the reduced risk of serious clinical outcomes. Better understanding of the longer-term consequences of the observed reductions in BMD is needed.

Clinical Trials Registration: NCT00867048. © 2017 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555813PMC
September 2017

Evolving Failures in the Delivery of Human Immunodeficiency Virus Care: Lessons From a Ugandan Meningitis Cohort 2006-2016.

Open Forum Infect Dis 2017 19;4(2):ofx077. Epub 2017 Apr 19.

Department of Medicine, University of Minnesota Medical School, Minneapolis.

Background: Because of investments in human immunodeficiency virus (HIV) care in sub-Saharan Africa, the number of people aware of their status and receiving antiretroviral therapy (ART) has increased; however, HIV/acquired immune deficiency syndrome (AIDS) mortality still remains high.

Methods: We performed retrospective analysis of 3 sequential prospective cohorts of HIV-infected Ugandan adults presenting with AIDS and meningitis from 2006 to 2009, 2010 to 2012, and 2013 to 2016. Participants were categorized as follows: (1) unknown HIV status; (2) known HIV without ART; (3) known HIV with previous ART. We further categorized 2006 and 2013 cohort participants by duration of HIV-status knowledge and of ART receipt.

Results: We screened 1353 persons with suspected meningitis. was the most common pathogen (63%). Over the decade, we observed an absolute increase of 37% in HIV status knowledge and 59% in antecedent ART receipt at screening. The 2006 cohort participants were new/recent HIV diagnoses (65%) or known HIV but not receiving ART (35%). Many 2013 cohort participants were new/recent HIV diagnoses (34%) and known HIV with <1 month ART (20%), but a significant proportion were receiving ART 1-4 months (11%) and >4 months (30%). Four percent of participants discontinued ART. From 2010 to 2016, meningitis cases per month increased by 33%.

Conclusions: Although improved HIV screening and ART access remain much-needed interventions in resource-limited settings, greater investment in viral suppression and opportunistic infection care among the growing HIV-infected population receiving ART is essential to reducing ongoing AIDS mortality.
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http://dx.doi.org/10.1093/ofid/ofx077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451663PMC
April 2017

Spinal Cord Stimulation (SCS)-The Implantable Systems Performance Registry (ISPR).

Neuromodulation 2016 Dec 12;19(8):857-863. Epub 2016 Oct 12.

Casa Colina Centers for Rehabilitation, Pomona, CA, USA.

Objectives: The Implantable Systems Performance Registry (ISPR) was created to monitor the product performance of Medtronic Spinal Cord Stimulation (SCS) and implanted intrathecal drug infusion systems available in the United States.

Materials And Methods: Data were collected on 2605 patients from 44 centers from various geographic regions across the United States implanting and following patients with SCS systems between June 25, 2004 and January 31, 2014. Actuarial life table methods are used to estimate device performance over time. Of the 2605 patients, 1490 (57.2%) were female, 1098 (42.1%) were male and 17 (0.7%) did not provide gender data. The average age at enrollment was 56.3 years (range: 4-97, SD = 14.3) and average follow-up time was 20.1 months (SD = 22.5).

Results: Currently the estimates of device survival from neurostimulator-related events exceed 97% for all neurostimulator models across the applicable follow-up time points and all applicable extension models had greater than 95% survival from extension events. The majority of product performance events were lead-related. At 5 years of follow-up, all applicable lead families, with the exception of the Pisces-Quad LZ family, had greater than 75% survival from lead events.

Conclusions: The ISPR is designed to serve as an ongoing source of system and device-related information with a focus on "real-world" safety and product performance. ISPR data continue to be used to guide future product development efforts aimed at improving product reliability and quality.
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http://dx.doi.org/10.1111/ner.12477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5157722PMC
December 2016

Intrathecal Drug Delivery Systems (IDDS): The Implantable Systems Performance Registry (ISPR).

Neuromodulation 2016 Dec 12;19(8):848-856. Epub 2016 Oct 12.

Medtronic, plc, Minneapolis, MN, USA.

Objectives: The ISPR was initially created to monitor the product performance of Medtronic implanted intrathecal drug infusion and spinal cord systems available in the United States.

Materials And Methods: Data were collected from 50 representative sites implanting and following patients with intrathecal drug delivery systems across the United States between August 7, 2003 and January 31, 2014. Device performance over time was estimated using life table survival methods.

Results: Of the 6093 patients enrolled in the ISPR, 3405 (55.9%) were female and 2675 (43.9%) were male, and 13 (0.2%) did not provide gender data. The average age at enrollment was 52.9 years (SD =17.6 years) and average follow-up time was 29.6 months. Currently, the estimates of device survival from pump-related events exceed 90% for all pump models across the applicable follow-up time points. The majority of product performance events were catheter-related. At 5 years of follow-up, all applicable catheter models, with the exception of revised not as designed or grafted not as designed catheters, had greater than 81% survival from catheter-related events.

Conclusions: The ISPR is designed to serve as an ongoing source of system and device-related information with a focus on "real-world" safety and product performance. ISPR data continue to be used to guide future product development efforts aimed at improving product reliability and quality.
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http://dx.doi.org/10.1111/ner.12524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5157772PMC
December 2016

Relationship between inflammatory and coagulation biomarkers and cardiac autonomic function in HIV-infected individuals.

Biomark Med 2014 ;8(9):1073-83

Center for Integrative Medicine, Wake Forest Baptist Health, Winston Salem, NC, USA.

Aim: To examine the relationship between inflammatory and coagulation biomarkers and cardiac autonomic function (CAF) as measured by heart rate variability in persons with HIV.

Materials & Methods: This analysis included 4073 HIV-infected persons from the Strategies for Management of Antiretroviral Therapy study. We examined the association between IL-6, high-sensitivity C-reactive protein (hsCRP) and D-dimer with heart rate variability measures (SDNN and rMSSD), both cross-sectionally and longitudinally.

Results: Cross-sectional analysis revealed significant inverse associations between IL-6, hsCRP and d-dimer with SDNN and rMSSD (p < 0.01 for all comparisons). However, longitudinal analysis failed to show a significant association between baseline IL-6, hsCRP and d-dimer with change in CAF over time.

Conclusion: Cross-sectionally, higher levels of inflammatory and coagulation biomarkers were associated with lower levels of CAF in the Strategies for Management of Antiretroviral Therapy trial. Although deterioration in CAF was observed during followup, baseline levels of inflammatory and coagulation markers were not predictive of the decline in CAF over time.
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http://dx.doi.org/10.2217/bmm.14.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278423PMC
July 2015

Race/ethnicity and HAART initiation in a military HIV infected cohort.

AIDS Res Ther 2014 Jan 24;11(1):10. Epub 2014 Jan 24.

Department of Preventive Medicine and Biometrics, Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Background: Prior studies have suggested that HAART initiation may vary by race/ethnicity. Utilizing the U.S. military healthcare system, which minimizes confounding from healthcare access, we analyzed whether timing of HAART initiation and the appropriate initiation of primary prophylaxis among those at high risk for pneumocystis pneumonia (PCP) varies by race/ethnicity.

Methods: Participants in the U.S. Military HIV Natural History Study from 1998-2009 who had not initiated HAART before 1998 and who, based on DHHS guidelines, had a definite indication for HAART (CD4 <200, AIDS event or severe symptoms; Group A), an indication to consider HAART (including CD4 <350; Group B) or electively started HAART (CD4 >350; Group C) were analyzed for factors associated with HAART initiation. In a secondary analysis, participants were also evaluated for factors associated with starting primary PCP prophylaxis within four months of a CD4 count <200 cells/mm3. Multiple logistic regression was used to compare those who started vs. delayed therapy; comparisons were expressed as odds ratios (OR).

Results: 1262 participants were evaluated in the analysis of HAART initiation (A = 208, B = 637, C = 479 [62 participants were evaluated in both Groups A and B]; 94% male, 46% African American, 40% Caucasian). Race/ethnicity was not associated with HAART initiation in Groups A or B. In Group C, African American race/ethnicity was associated with lower odds of initiating HAART (OR 0.49, p = 0.04). Race and ethnicity were also not associated with the initiation of primary PCP prophylaxis among the 408 participants who were at risk.

Conclusions: No disparities in the initiation of HAART or primary PCP prophylaxis according to race/ethnicity were seen among those with an indication for therapy. Among those electively initiating HAART at the highest CD4 cell counts, African American race/ethnicity was associated with decreased odds of starting. This suggests that free healthcare can potentially overcome some of the observed disparities in HIV care, but that unmeasured factors may contribute to differences in elective care decisions.
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http://dx.doi.org/10.1186/1742-6405-11-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3922739PMC
January 2014

Determinants of developing widened spatial QRS-T angle in HIV-infected individuals: results from the Strategies for Management of Antiretroviral Therapy [SMART] Study.

J Electrocardiol 2014 Mar-Apr;47(2):264-71. Epub 2013 Dec 4.

Department of Internal Medicine, Secion on Cardiology, Wake Forest School of Medicine, Winston Salem, NC, USA; Epidemiological Cardiology Research Center (EPICARE), Wake Forest School of Medicine, Winston Salem, NC, USA. Electronic address:

Background: A widened electrocardiographic spatial QRS-T angle has been shown to be predictive of cardiovascular disease in HIV-infected individuals. However, determinants and risk factors of developing widened QRS-T angle over time in this population remain unknown.

Methods And Results: Spatial QRS-T angle was automatically measured from standard electrocardiogram of 1444 HIV-infected individuals without baseline widened spatial QRS-T angle from the Strategies for Management of Antiretroviral Therapy [SMART], a clinical trial comparing two antiretroviral treatment strategies [Drug Conservation (DC) vs. Viral Suppression (VS)]. Conditional logistic regression analysis was used to examine the association between baseline characteristics and incident widened spatial QRS-T angle (a new angle>93° in males and>74° in females). During 2544 person-years of follow-up, 199 participants developed widened angle at a rate of 7.8 per 100 person-years. In unadjusted models, female sex, black race (vs. white), DC treatment strategy, current and past smokers (vs. never), history of alcohol abuse, greater body mass index, history of diabetes and higher levels of hs-C-reactive protein were associated with incident widened spatial QRS-T angle. When these variables were entered together in the same model with adjustment for demographics and treatment strategy, DC treatment strategy [OR (95% CI): 1.50 (1.09, 2.07)], female gender [1.69 (1.17, 2.45)], current and past smoking (vs. never) [2.49 (1.63, 3.81) and 1.93 (1.21, 3.09), respectively], and diabetes [2.28 (1.33, 3.91)] predicted incident widened spatial QRS-T angle.

Conclusions: Drug conservation treatment strategy, female gender, smoking, and diabetes are independently predictive of incident widened spatial QRS-T angle in HIV-infected individuals.
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http://dx.doi.org/10.1016/j.jelectrocard.2013.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951578PMC
November 2014

Improved neurocognitive test performance in both arms of the SMART study: impact of practice effect.

J Neurovirol 2013 Aug 14;19(4):383-92. Epub 2013 Aug 14.

Coordinating Center for Biometric Research, University of Minnesota, Minneapolis, MN 55414, USA.

We evaluated factors associated with improvement in neurocognitive performance in 258 HIV-infected adults with baseline CD4 lymphocyte counts above 350 cells/mm³ randomized to intermittent, CD4-guided antiretroviral therapy (ART) (128 participants) versus continuous therapy (130) in the Neurology substudy of the Strategies for Management of Antiretroviral Therapy trial. Participants were enrolled in Australia, North America, Brazil, and Thailand, and neurocognitive performance was assessed by a five-test battery at baseline and month 6. The primary outcome was change in the quantitative neurocognitive performance z score (QNPZ-5), the average of the z scores of the five tests. Associations of the 6-month change in test scores with ART use, CD4 cell counts, HIV RNA levels, and other factors were determined using multiple regression models. At baseline, median age was 40 years, median CD4 cell count was 513 cells/mm³, 88 % had plasma HIV RNA ≤ 400 copies/mL, and mean QNPZ-5 was -0.68. Neurocognitive performance improved in both treatment groups by 6 months; QNPZ-5 scores increased by 0.20 and 0.13 in the intermittent and continuous ART groups, respectively (both P < 0.001 for increase and P = 0.26 for difference). ART was used on average for 3.6 and 5.9 out of the 6 months in the intermittent and continuous ART groups, respectively, but the increase in neurocognitive test scores could not be explained by ART use, changes in CD4, or plasma HIV RNA, which suggests a practice effect. The impact of a practice effect after 6 months emphasizes the need for a control group in HIV studies that measure intervention effects using neurocognitive tests similar to ours.
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http://dx.doi.org/10.1007/s13365-013-0190-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963803PMC
August 2013

Protease inhibitors and cardiac autonomic function in HIV-infected patients: a cross-sectional analysis from the Strategies for Management of Antiretroviral Therapy (SMART) Trial.

BMJ Open 2013 Mar 6;3(3). Epub 2013 Mar 6.

Epidemiological Cardiology Research Center (EPICARE), Division of Public Health Sciences Wake Forest School of Medicine, Division of Public Health Sciences, Winston Salem, North Carolina, USA.

Objective: To compare cardiac autonomic function as measured by heart rate variability for HIV-infected participants taking protease inhibitors (PIs) with those taking a non-nucleoside reverse transcriptase inhibitor without a PI (NNRTI-no PI) regimen.

Design: Cross-sectional analysis.

Setting: Multicentre study.

Participants: 2998 participants (average age 44 years, 28% females) enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) trial.

Primary Outcome Measures: Heart rate and two heart rate variability measures (the SD of all filtered RR intervals over the length of the recording (SDNN) and the root mean square of successive differences in normal RR intervals (rMSSD)).

Results: At study entry, 869 participants were taking a boosted PI (PI/r), 579 a non-boosted PI and 1550 an NNRTI-no PI. Median values (IQR) of heart rate, SDNN and rMSSD were: 68 (60-75) beats/min (bpm), 21 (13-33) ms, 22 (13-35) ms in the PI/r group, 68 (60-75) bpm, 21 (13-33) ms and 21 (14-33) ms in the non-boosted PI group and 69 (62-77) bpm, 20 (13-31) ms and 21(13-33) ms in the NNRTI-no PI group. After adjustment for baseline factors, for those given PI/r and non-boosted PI, heart rate was 2.2 and 2.8 bpm, respectively, lower than the NNRTI-no PI group (p<0.001 for both). On the other hand, compared with the NNRTI-no PI group, log SDNN and log rMSSD were significantly greater for those in the non-boosted PI (p values for baseline adjusted differences in log-transformed SDNN and rMSSD were 0.004 and 0.001) but not for those in the PI/r group at the 0.01 α-level.

Conclusions: Compared to an NNRTI-no PI regimen, heart rate was lower for those taking a PI/r or non-boosted PI and heart rate variability was greater, reflecting better cardiac autonomic function, for those taking a non-boosted PI regimen but not PI/r.
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http://dx.doi.org/10.1136/bmjopen-2012-002523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612790PMC
March 2013

Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy.

J Bone Miner Res 2013 Jun;28(6):1264-74

The Alfred Hospital and Monash University, Melbourne, Australia.

Bone mineral density (BMD) declines significantly in HIV patients on antiretroviral therapy (ART). We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy (SMART) trial and determined whether early changes in markers predicted subsequent change in BMD. For 202 participants (median age 44 years, 17% female, 74% on ART) randomized to continuous or intermittent ART, plasma markers of inflammation and bone turnover were evaluated at baseline and months 4 and 12; BMD at the spine (dual-energy X-ray absorptiometry [DXA] and computed tomography) and hip (DXA) was evaluated annually. Compared with the continuous ART group, mean bone-specific alkaline phosphatase (bALP), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), N-terminal cross-linking telopeptide of type 1 collagen (NTX), and C-terminal cross-linking telopeptide of type 1 collagen (βCTX) decreased significantly in the intermittent ART group, whereas RANKL and the RANKL:osteoprotegerin (OPG) ratio increased (all p ≤ 0.002 at month 4 and month 12). Increases in bALP, osteocalcin, P1NP, NTX, and βCTX at month 4 predicted decrease in hip BMD at month 12, whereas increases in RANKL and the RANKL:OPG ratio at month 4 predicted increase in hip and spine BMD at month 12. This study has shown that compared with continuous ART, interruption of ART results in a reduction in markers of bone turnover and increase in BMD at hip and spine, and that early changes in markers of bone turnover predict BMD changes at 12 months.
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http://dx.doi.org/10.1002/jbmr.1861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657331PMC
June 2013

Identification of an abbreviated test battery for detection of HIV-associated neurocognitive impairment in an early-managed HIV-infected cohort.

PLoS One 2012 8;7(11):e47310. Epub 2012 Nov 8.

HIV Neurobehavioral Research Program, San Diego, California, United States of America.

Background: HIV-associated neurocognitive disorders (HAND) remain prevalent despite improved antiretroviral treatment (ART), and it is essential to have a sensitive and specific HAND screening tool.

Methods: Participants were 200 HIV-infected US military beneficiaries, managed early in the course of HIV infection, had few comorbidities, and had open access to ART. Participants completed a comprehensive, seven-domain (16-test), neuropsychological battery (∼120 min); neurocognitive impairment (NCI) was determined using a standardized score derived from demographically adjusted T-scores (global deficit score ≥0.5). Restricting the estimated administration time of the screening battery to < = 20 minutes, we examined the sensitivity and specificity of detecting NCI for all possible combinations of 2-, 3-, and 4- tests from the comprehensive battery.

Results: Participants were relatively healthy (median CD4 count: 546 cells/mm(3)) with 64% receiving ART. Prevalence of NCI was low (19%). The best 2-test screener included the Stroop Color Test and the Hopkins Verbal Learning Test-Revised (11 min; sensitivity = 73%; specificity = 83%); the best 3-test screener included the above measures plus the Paced Auditory Serial Addition Test (PASAT; 16 min; sensitivity = 86%; specificity = 75%). The addition of Action Fluency to the above three tests improved specificity (18 min; sensitivity = 86%; specificity = 87%).

Conclusions: Combinations of widely accepted neuropsychological tests with brief implementation time demonstrated good sensitivity and specificity compared to a time intensive neuropsychological test battery. Tests of verbal learning, attention/working memory, and processing speed are particularly useful in detecting NCI. Utilizing validated, easy to administer, traditional neuropsychological tests with established normative data may represent an excellent approach to screening for NCI in HIV.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0047310PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493574PMC
April 2013

Electrocardiographic spatial QRS-T angle and incident cardiovascular disease in HIV-infected patients (from the Strategies for the Management of Antiretroviral Therapy [SMART] study).

Am J Cardiol 2013 Jan 9;111(1):118-24. Epub 2012 Oct 9.

Department of Internal Medicine, Section on Cardiology, Wake Forest School of Medicine, Winston Salem, NC, USA.

Widening of the electrocardiographic (ECG) spatial QRS-T angle has been predictive of cardiovascular disease (CVD) events in the general population. However, its prognostic significance in human immunodeficiency virus (HIV)-infected patients remains unknown. The spatial QRS-T angle was derived from the baseline resting 12-lead electrocardiogram of 4,453 HIV-infected patients aged 43.5 ± 9.3 years from the Strategies for Management of Antiretroviral Therapy (SMART) trial. CVD events were identified during a median follow-up of 28.7 months. Quartiles of the spatial QRS-T angle was calculated for men and women separately, and values in the upper quartile were considered as a widened angle (values >74° for women and >93° for men). A multivariate Cox proportional hazards analysis was used to examine the association between a widened baseline spatial QRS-T angle and incident CVD events. During 11,965 person-years of follow-up, 152 CVD events occurred at a rate of 1.27 events/100 person-years. The rate of CVD events in those with a widened spatial QRS-T angle was almost double the rate in those with a normal spatial QRS-T angle (rate ratio 1.94, 95% confidence interval 1.40 to 2.69; p <0.001). In a model adjusted for study treatment arm, demographics, CVD risk factors, HIV characteristics, inflammatory markers, and other ECG abnormalities, a widened spatial QRS-T angle was associated with a >50% increased risk of CVD events compared to a normal spatial QRS-T angle (hazard ratio 1.53, 95% confidence interval 1.07 to 2.17; p = 0.02). No interaction was seen by SMART trial arm (p value for interaction = 0.37) or gender (p value for interaction = 0.84). In conclusion, a widened spatial QRS-T angle was independently predictive of CVD events in HIV-infected patients receiving antiretroviral therapy. This highlights the potential role of routine electrocardiography as a simple noninvasive CVD risk-screening tool in HIV-infected patients.
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http://dx.doi.org/10.1016/j.amjcard.2012.08.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525800PMC
January 2013

Prevalence and factors associated with sleep disturbances among early-treated HIV-infected persons.

Clin Infect Dis 2012 May 19;54(10):1485-94. Epub 2012 Mar 19.

Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.

Background: Sleep disturbances are reportedly common among persons infected with human immunodeficiency virus (HIV), but recent data, including comparisons with HIV-uninfected persons, are limited.

Methods: We performed a cross-sectional study among early-treated HIV-infected military beneficiaries (n = 193) to determine the prevalence and factors associated with insomnia (Pittsburgh Sleep Quality Index [PSQI]) and daytime sleepiness (Epworth Sleepiness Scale [ESS]). Data were compared with HIV-uninfected persons (n = 50) matched by age, sex, race or ethnicity, and military rank.

Results: Forty-six percent of HIV-infected persons had insomnia (PSQI >5), and 30% reported daytime drowsiness (ESS ≥10). The prevalence of insomnia and daytime sleepiness was not significantly higher compared with the HIV-uninfected group (38% [P = .30] and 20% [P = .18], respectively). In the multivariate model, factors associated with insomnia among HIV infected patients included depression (odds ratio [OR], 16.8; 95% confidence interval [CI], 2.0-142.1; P = .01), increased waist size (OR, 2.7; 95% CI, 1.4-5.1; P = .002), and fewer years of education (OR, 0.8; 95% CI, .7-.95; P = .006). Neurocognitive impairment (diagnosed in 19% of HIV-infected participants) was not associated with insomnia; however, HIV-infected persons with insomnia were 3.1-fold more likely to have a decline in activities of daily living than those without insomnia (23% vs 9%; P = .01). Only 18% of HIV-infected persons reported using a sleep medication at least weekly.

Conclusions: HIV-infected persons have a high prevalence of insomnia, but among an early-treated cohort this rate was not significantly higher compared with HIV-uninfected persons. Factors associated with insomnia among HIV-infected patients include depression and increased waist size. Prompt diagnosis and treatment of sleep disturbances are advocated and may improve quality of life.
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http://dx.doi.org/10.1093/cid/cis192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334363PMC
May 2012

Hepatitis B virus coinfection negatively impacts HIV outcomes in HIV seroconverters.

J Infect Dis 2012 Jan 5;205(2):185-93. Epub 2011 Dec 5.

Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences.

Background: Understanding the impact of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) coinfection has been limited by heterogeneity of HIV disease. We evaluated HBV coinfection and HIV-related disease progression in a cohort of HIV seroconverters.

Methods: Participants with HIV diagnosis seroconversion window of ≤ 3 years and serologically confirmed HBV infection (HB) status were classified at baseline into 4 HB groups. The risk of clinical AIDS/death in HIV seroconverters was calculated by HB status.

Results: Of 2352 HIV seroconverters, 474 (20%) had resolved HB, 82 (3%) had isolated total antibody to hepatitis B core antigen (HBcAb), and 64 (3%) had chronic HB. Unadjusted rates (95% confidence intervals [CIs]) of clinical AIDS/death for the HB-negative, resolved HB, isolated HBcAb, and chronic HB groups were 2.43 (2.15-2.71); 3.27 (2.71-3.84); 3.75 (2.25-5.25); and 5.41 (3.41-7.42), respectively. The multivariable risk of clinical AIDS/death was significantly higher in the chronic HB group compared to the HB-negative group (hazard ratio [HR], 1.80; 95% CI, 1.20-2.69); while the HRs were increased but nonsignificant for those with resolved HB (HR, 1.17; 95% CI, .94-1.46) and isolated HBcAb (HR, 1.14; 95% CI, .75-1.75).

Conclusions: HBV coinfection has a significant impact on HIV outcomes. The hazard for an AIDS or death event is almost double for those with chronic HB compared, with HIV-monoinfected persons.
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http://dx.doi.org/10.1093/infdis/jir720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244364PMC
January 2012

Development of chronic hepatitis B virus infection in hepatitis B surface antigen negative HIV/HBV co-infected adults: a rare opportunistic illness.

J Med Virol 2011 Sep;83(9):1537-43

Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Infectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, Texas.

Changes in serologic status in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infected individuals with either isolated anti-HBc or resolved HBV infection have been reported, but the frequency of clinically meaningful long-term serologic changes is not well-defined. This study therefore, examined longitudinal serologic status for hepatitis B surface antigen (HBsAg)-negative HIV/HBV co-infected participants in a large cohort. Among 5,222 cohort participants, 347 (7%) were initially isolated anti-HBc positive, and 1,073 (21%) had resolved HBV infection (concurrently reactive for anti-HBc and anti-HBs). Thirty-three (10%) of the 347 participants with isolated anti-HBc were later positive for HBsAg at least once, compared with 3 (0.3%) of those with resolved HBV (P < 0.001). A total of 14 participants became persistently positive for HBsAg and were thus classified as having late-onset chronic HBV infection at a median of 3.7 years after initial HBV diagnosis. For those initially with HBsAg-negative HIV/HBV co-infection, the rate of late-onset chronic HBV infection was 1.39/1,000 person-years. Those with late-onset chronic HBV infection experienced significant decreases in CD4 cell counts (P = 0.002) with a mean of 132 cells/µl at the time of late-onset chronic HBV infection, but no factor distinguished those who were positive for HBsAg only once from those that developed late-onset chronic HBV infection. Over a median of 2.9 years following late-onset chronic HBV infection, 3 of 14 subsequently lost HBsAg. The occurrence of late-onset chronic HBV infection in HBsAg negative HIV/HBV co-infected adults appears to be one important, albeit rare, clinical event seen almost exclusively in those with isolated anti-HBc and low CD4 cell count.
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http://dx.doi.org/10.1002/jmv.22155DOI Listing
September 2011

Impact of weight on immune cell counts among HIV-infected persons.

Clin Vaccine Immunol 2011 Jun 27;18(6):940-6. Epub 2011 Apr 27.

Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.

Prior studies have shown that weight may impact immune cell counts. However, few data exist about the relationship of weight and immune cell counts among HIV-infected patients. We examined documented HIV seroconverters (mean window, 15.7 months) in a prospective U.S. Military HIV Natural History Study (1 January 1986 to 20 January 2010). We estimated the association of the time-updated body mass index (BMI) category with changes in immune cell counts from HIV diagnosis across time (mean follow-up of 5.1 years) using multiply adjusted longitudinal linear mixed-effects models. Of 1,097 HIV seroconverters, 448 (41%) were overweight and 93 (8%) were obese at HIV diagnosis. Immune cell counts at HIV diagnosis did not significantly differ by BMI category. In the longitudinal models for those diagnosed before the advent of the highly active antiretroviral therapy (HAART) era, mean postdiagnosis decreases in the white cell count, total lymphocyte count, CD4 count, CD4 percentage, and CD4/CD8 ratio were less as the BMI category increased (all with P values of <0.05). Among HIV seroconverters diagnosed in the HAART era, obese compared to normal-weight patients had significantly smaller increases in CD4 counts, CD4 percentages, and the CD4/CD8 ratio (all with P values of <0.05). Similar findings were also noted among underweight versus normal-weight patients. In conclusion, although BMI was not associated with immune cell levels at the time of HIV diagnosis, weight appears to affect immune cells counts over the course of infection. In the HAART era, being either underweight or obese was associated with smaller increases in several important immune cell levels, including the CD4/CD8 ratio.
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http://dx.doi.org/10.1128/CVI.00020-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122603PMC
June 2011

Long-term safety and serologic response to measles, mumps, and rubella vaccination in HIV-1 infected adults.

Vaccine 2011 Apr 23;29(16):2874-80. Epub 2011 Feb 23.

Brooke Army Medical Center, San Antonio, TX, United States.

We analyzed HIV viral load (VL) and CD4 count changes, and antibody responses following MMR vaccination of individuals in the U.S. Military HIV Natural History Study cohort. Cases receiving at least one dose of MMR vaccine after HIV diagnosis were matched 1:2 to HIV-positive controls not receiving the vaccine. Baseline was defined as time of vaccination for cases and indexed and matched to the time post-HIV diagnosis for controls. Changes in CD4 count and VL at 6, 12, 18 and 24 months were compared between cases and controls using a general linear model. Available sera from cases were tested for MMR seropositivity at baseline and post-vaccination at 6, 12, 18, and 24 months. Overall mean CD4 count change from baseline through 24 months was 20 (±23) cells/μL greater for cases than controls (p=0.39). Similar non-significant changes in CD4 cell count were seen in the subset of those not on HAART at baseline. VL changes were small and similar between groups (mean differential change -0.04 (±0.18) log(10) copies/mL; p=0.84). Of 21 vaccinated participants with baseline serologic testing, 14 (67%) were reactive to measles, 19 (91%) to mumps, and 20 (95%) to rubella. Three (43%) of 7 participants nonreactive to measles developed measles IgG; for mumps, 1 (50%) of 2 developed mumps IgG; for rubella, 1 (100%) developed rubella IgG. MMR vaccination did not result in detrimental immunologic or virologic changes through 24 months post-vaccination.
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http://dx.doi.org/10.1016/j.vaccine.2011.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073409PMC
April 2011

Boosted protease inhibitors and the electrocardiographic measures of QT and PR durations.

AIDS 2011 Jan;25(3):367-77

Epidemiological Cardiology Research Center, Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston Salem, North Carolina 27104, USA.

Background: There are contradictory reports regarding the effects of protease inhibitors on the ECG measures of QT and PR interval durations. The effect of interrupting use of protease inhibitors on QT and PR progression is also unknown.

Methods: This analysis included 3719 participants from the Strategies for Management of Antiretroviral Therapy (SMART) study, of whom 1879 were randomized to receive intermittent antiretroviral therapy (ART) (drug conservation group), whereas the rest received these drugs continuously (viral suppression group). Linear regression analysis was used to compare four ritonavir-boosted protease inhibitor (protease inhibitor/r) regimens [saquinavir (SQV/r), lopinavir (LPV/r), atazanavir (ATV/r), and other protease inhibitor/r], and nonboosted protease inhibitor regimens with nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens for Bazett's (QTcB) and Fredericia's (QTcF) heart rate corrected QT and PR. Changes in QTcB, QTcF, and PR after 12 and 24 months of randomization were compared in the drug conservation group and viral suppression group.

Results: Average levels of QTcB, QTcF, and PR duration at entry were 415, 406, and 158 ms. At study entry, 49% of participants were taking an NNRTI (no protease inhibitor)-based regimen and 31% were prescribed a boosted protease inhibitor, the most common being LPV/r. After adjustment for baseline factors, QTcB and QTcF levels did not vary by boosted protease inhibitor group (P = 0.26 and P = 0.34, respectively). For those given any of the boosted protease inhibitors, QTcB was 1.5 ms lower than the NNRTI group (P = 0.04). Both boosted and nonboosted protease inhibitor-containing regimens were significantly associated (P < 0.01 for each) with longer PR intervals compared to the NNRTI group. After adjustment, the difference between boosted protease inhibitors and the NNRTI group was 5.11 ms (P < 0.01); for nonboosted protease inhibitors, this difference was 3.00 ms (P < 0.01). Following ART interruption, PR duration declined for both the boosted and nonboosted protease inhibitor groups and compared to the viral suppression group, significant changes in PR interval were observed 24 months after ART interruption of boosted protease inhibitors (P < 0.01).

Conclusion: Different protease inhibitor-based regimens have a similar, minimal effect on QT compared to NNRTI-based regimens. All protease inhibitor-based regimens (boosted and nonboosted) were associated with prolongation of PR, and interruption of protease inhibitor regimens reduced the prolonged PR duration. Further research is needed to confirm the findings of this study and assess the clinical relevance of the differences.
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http://dx.doi.org/10.1097/QAD.0b013e328341dcc0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111078PMC
January 2011

Prevalence and prognostic significance of ECG abnormalities in HIV-infected patients: results from the Strategies for Management of Antiretroviral Therapy study.

J Electrocardiol 2011 Nov-Dec;44(6):779-85. Epub 2010 Dec 8.

Epidemiological Cardiology Research Center, Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, NC 27104, USA.

Background: It remains debated whether to include resting electrocardiogram (ECG) in the routine care of human immunodeficiency virus (HIV)-infected patients.

Methods: This analysis included 4518 HIV-infected patients (28% women and 29% blacks) from the Strategies for Management of Antiretroviral Therapy study, a clinical trial aimed to compare 2 HIV treatment strategies. ECG abnormalities were classified using the Minnesota Code. Cox proportional hazards analysis was used to examine the association between baseline ECG abnormalities and incident cardiovascular disease (CVD).

Results: More than half of the participants (n = 2325, or 51.5%) had either minor or major ECG abnormalities. Minor ECG abnormalities (48.6%) were more common than major ECG abnormalities (7.7%). During a median follow-up of 28.7 months, 155 participants (3.4%) developed incident CVD. After adjusting for the study-treatment arms, the presence of major, minor, and either minor or major ECG abnormalities was significantly predictive of incident CVD (hazard ratio [95% confidence interval]: 2.76 [1.74-4.39], P < .001; 1.58 [1.14-2.20], P = .006; 1.57 [1.14-2.18], P = .006, respectively). However, after adjusting for demographics, CVD risk factors, and HIV characteristics (full model), presence of major ECG abnormalities were still significantly predictive of CVD (1.83 [1.12-2.97], P = .015) but not minor or major abnormalities taken together (1.26 [0.89-1.79], P = .18; 1.25 [0.89-1.76], P = .20, respectively). Individual ECG abnormalities that significantly predicted CVD in the fully adjusted model included major isolated ST-T abnormalities, major prolongation of QT interval, minor isolated ST-T, and minor isolated Q-QS abnormalities.

Conclusion: Nearly 1 in 2 of the HIV-infected patients in our study had ECG abnormalities; 1 in 13 had major ECG abnormalities. Presence of ECG abnormalities, especially major ECG abnormalities, was independently predictive of incident CVD. These results suggest that the ECG could provide a convenient risk-screening tool in HIV-infected patients.
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http://dx.doi.org/10.1016/j.jelectrocard.2010.10.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060290PMC
February 2012

The association of ethnicity with antibody responses to pneumococcal vaccination among adults with HIV infection.

Vaccine 2010 Nov 29;28(48):7583-8. Epub 2010 Sep 29.

Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.

Ethnicity may be associated with the incidence of pneumococcal infections and the frequency of protective vaccine responses. Earlier studies have suggested that HIV-infected persons of black ethnicity develop less robust immune responses to pneumococcal vaccination that may relate to their higher incidence of invasive disease. We evaluated the association of ethnicity with capsule-specific antibody responses to pneumococcal revaccination, with either the pneumococcal conjugate (PCV) or polysaccharide (PPV) vaccines among 188 HIV-infected adults. The proportion of the 77 African Americans (AA) and 111 Caucasians with comparable virologic and immunologic parameters who achieved a positive immune response (≥2-fold rise in capsule-specific IgG from baseline with post-vaccination value ≥1 μg/mL for ≥2 of 4 serotypes) at day 60 after revaccination was similar (43% vs. 49%, respectively, p=0.65). Results were also similar when vaccine types (PPV and PCV) were examined separately. Mean changes in log(10) transformed IgG levels from baseline to days 60 and 180 post-vaccination were also not significantly different between AA and Caucasians. In summary, in this ethnically diverse cohort with equal access to care, we did not observe differential antibody responses between AA and Caucasian HIV-infected adults after pneumococcal revaccination.
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http://dx.doi.org/10.1016/j.vaccine.2010.09.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981674PMC
November 2010

A randomized clinical trial comparing revaccination with pneumococcal conjugate vaccine to polysaccharide vaccine among HIV-infected adults.

J Infect Dis 2010 Oct;202(7):1114-25

Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, National Naval Medical Center, Bethesda, Maryland 92134-1005, USA.

Background: The risk of pneumococcal disease persists, and antibody responses to revaccination with the 23-valent polysaccharide vaccine (PPV) are low among human immunodeficiency virus (HIV)-infected adults. We determined whether revaccination with the 7-valent pneumococcal conjugate vaccine (PCV) would enhance these responses.

Methods: In a randomized clinical trial, we compared the immunogenicity of revaccination with PCV ( n = 131) or PPV (n = 73) among HIV-infected adults (median CD4 cell count, 533 cells/mm(3)) who had been vaccinated with PPV 3-8 years earlier. HIV-uninfected adults (n = 25) without prior pneumococcal vaccination received 1 dose of PCV. A positive response was defined as a >or=2-fold increase (from baseline to day 60) in capsule-specific immunoglobulin G, with a postvaccination level >or=1000 ng/mL for at least 2 of the 4 serotypes.

Results: HIV-infected persons demonstrated a higher frequency of positive antibody responses to PCV than to PPV (57% vs 36%) (P = .004) and greater mean changes in the immunoglobulin G concentration from baseline to day 60 for serotypes 4, 9V, and 19F (P < .05, for all), but not for serotype 14. However, by day 180, both outcomes were similar. Responses to PCV were greater in frequency and magnitude for all serotypes in HIV-uninfected adults, compared with those in HIV-infected adults.

Conclusions: Among persons with HIV infection, revaccination with PCV was only transiently more immunogenic than PPV, and responses were inferior to those in HIV-uninfected subjects with primary vaccination. Pneumococcal vaccines with more robust and sustained immunogenicity are needed for HIV-infected adults. Clinical trial registration. ClinicalTrials.gov identifier NCT00622843.
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http://dx.doi.org/10.1086/656147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2932785PMC
October 2010

Increasing rates of obesity among HIV-infected persons during the HIV epidemic.

PLoS One 2010 Apr 9;5(4):e10106. Epub 2010 Apr 9.

Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.

Background: The prevalence and factors associated with overweight/obesity among human immunodeficiency virus (HIV)-infected persons are unknown.

Methods: We evaluated prospective data from a U.S. Military HIV Natural History Study (1985-2004) consisting of early diagnosed patients. Statistics included multivariate linear regression and longitudinal linear mixed effects models.

Results: Of 1682 patients, 2% were underweight, 37% were overweight, and 9% were obese at HIV diagnosis. Multivariate predictors of a higher body mass index (BMI) at diagnosis included more recent year of HIV diagnosis, older age, African American race, and earlier HIV stage (all p<0.05). The majority of patients (62%) gained weight during HIV infection. Multivariate factors associated with a greater increase in BMI during HIV infection included more recent year of diagnosis, lower BMI at diagnosis, higher CD4 count, lower HIV RNA level, lack of AIDS diagnosis, and longer HIV duration (all p<0.05). Nucleoside agents were associated with less weight gain; other drug classes had no significant impact on weight change in the HAART era.

Conclusions: HIV-infected patients are increasingly overweight/obese at diagnosis and during HIV infection. Weight gain appears to reflect improved health status and mirror trends in the general population. Weight management programs may be important components of HIV care.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0010106PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856157PMC
April 2010

Obesity among HIV-infected persons: impact of weight on CD4 cell count.

AIDS 2010 Apr;24(7):1069-72

Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.

To assess the effect of obesity on CD4 cell counts, we estimated the association of time-updated BMI categories with CD4 changes among 1001 documented HIV seroconverters. During the pre-highly active antiretroviral therapy (HAART) era, a higher BMI was associated with less reduction in CD4 cell counts over time. However during the HAART era, obese versus normal weight patients had smaller increases in CD4 cell counts (+69 versus +116 cells, P = 0.01). Lower CD4 cell counts may now be another adverse consequence of obesity.
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http://dx.doi.org/10.1097/QAD.0b013e328337fe01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2878190PMC
April 2010

Natural history of colonization with gram-negative multidrug-resistant organisms among hospitalized patients.

Infect Control Hosp Epidemiol 2010 Apr;31(4):330-7

Uniformed Services University of the Health Sciences, Infectious Disease Clinical Research Program, Bethesda, Maryland, USA.

Objective: To determine the anatomic sites and natural history of colonization with gram-negative multidrug-resistant organisms (MDROs).

Design: Prospective, longitudinal cohort study.

Setting: Walter Reed Army Medical Center, a 236-bed tertiary care center in Washington, DC.

Patients: Deployed subjects (ie, inpatients medically evacuated from Iraq or Afghanistan) or nondeployed subjects admitted to the same hospital.

Methods: Consenting patients had 6 anatomic sites cultured every 3 days for 2 weeks and then weekly. Gram-negative organisms resistant to 3 or more classes of antibiotics were considered MDROs. Isolates were genotyped using pulsed-field gel electrophoresis. Clinical data, data on antibiotic use, and clinical culture results were collected.

Results: Of 60 deployed subjects, 14 (23%) were colonized with an MDRO at admission, and 13 (22%) had incident colonization during hospitalization. The groin was the most sensitive anatomic site for detecting MDRO colonization, and all but one subject remained colonized for the duration of their hospitalization. Sixty percent of subjects with incident Acinetobacter colonization and 25% of subjects with incident Klebsiella colonization had strains that were related to those isolated from other subjects. Of 60 nondeployed subjects, 5 (8%) were colonized with an MDRO at admission; all had recent healthcare contact, and 1 nondeployed subject had an isolate related to a strain recovered from a deployed subject.

Conclusions: Colonization with gram-negative MDROs is common among patients with war-related trauma admitted to a military hospital and also occurs among nondeployed patients with recent healthcare contact. The groin is the most sensitive anatomic site for active surveillance, and spontaneous decolonization is rare.
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http://dx.doi.org/10.1086/651304DOI Listing
April 2010

The impact of nelfinavir exposure on cancer development among a large cohort of HIV-infected patients.

J Acquir Immune Defic Syndr 2009 Jul;51(3):305-9

Infectious Disease Clinical Research Program/TriService AIDS Clinical Consortium, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Background: Preclinical studies suggest that the antiretroviral agent, nelfinavir mesylate (NFV), may have antineoplastic properties. The relationship between NFV and cancer incidence among HIV-infected patients is unknown.

Methods: We evaluated the impact of NFV on cancer development in a large cohort of HIV-infected persons with 108 cancer events during 13,421 person-years of follow-up. Using multivariate time-updated Cox proportional hazard models, the risk of cancer among those receiving NFV were compared to those on non-NFV antiretroviral regimens.

Results: The risk of cancer among those receiving NFV was similar to those on non-NFV antiretroviral regimens (hazard ratio 1.0, 95% confidence interval 0.5, 1.7, P = 0.90). We also examined AIDS-defining and non-AIDS-defining cancers separately and found no significant associations between NFV use and cancer risk. Antiretroviral use, with or without a protease inhibitor (PI) component, was associated with a reduced risk of AIDS-defining cancers compared with no antiretroviral therapy; however, the risk of cancer was the same among those using PI or PI-sparing regimens.

Discussion: Despite reports that NFV may have tumoricidal activity, we found no significant relationship between NFV or PI use compared with other antiretrovirals and the risk of developing cancer among a large cohort of HIV-infected persons.
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http://dx.doi.org/10.1097/QAI.0b013e3181aa13c7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720269PMC
July 2009

Increasing age at HIV seroconversion from 18 to 40 years is associated with favorable virologic and immunologic responses to HAART.

J Acquir Immune Defic Syndr 2008 Sep;49(1):40-7

Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Background: Studies evaluating the effect of age on response to highly active antiretroviral therapy (HAART) have been limited by their inability to control for duration of human immunodeficiency virus (HIV) infection. We examined the effect of age at HIV seroconversion on response to HAART.

Methods: A retrospective analysis of a longitudinal US military cohort of HIV-infected subjects. Time to and maintenance of viral suppression, rate of CD4 cell increase, and rate of progression to acquired immunodeficiency syndrome or death were compared across age groups using time-to-event methods.

Results: Five hundred sixty-three HIV-infected adults who seroconverted after January 1, 1996, and started HAART were included. Increasing age at seroconversion was significantly associated with faster time to viral suppression (P = 0.002). Increasing age also correlated with duration of suppression, with a 35% reduction in risk of viral rebound for every 5-year increase in age above 18 years (hazard ratio: 0.65, 95% confidence interval 0.55 to 0.75). The rate of CD4 cell increase from 6 to 84 months post-HAART was significantly greater in those who seroconverted at older ages (P = 0.0002). Rates of progression to acquired immunodeficiency syndrome or death did not differ between groups.

Conclusions: Increasing age at seroconversion was associated with shorter time to and longer maintenance of viral suppression and a faster increase in CD4 cell count.
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http://dx.doi.org/10.1097/QAI.0b013e31817bec05DOI Listing
September 2008

Pneumonia in HIV-infected persons: increased risk with cigarette smoking and treatment interruption.

Am J Respir Crit Care Med 2008 Sep 10;178(6):630-6. Epub 2008 Jul 10.

Infectious Diseases (151B), Veterans Affairs Medical Center, 50 Irving Street, NW, Washington, DC 20422, USA.

Rationale: Bacterial pneumonia is a major cause of morbidity for HIV-infected persons and contributes to excess mortality in this population.

Objectives: To evaluate the frequency and risk factors for occurrence of bacterial pneumonia in the present era of potent antiretroviral therapy.

Methods: We evaluated data from a randomized trial of episodic antiretroviral therapy. The study, Strategies for Management of Antiretroviral Therapy, enrolled 5,472 participants at 318 sites in 33 countries. Study patients had more than 350 CD4 cells at baseline. Diagnosis of bacterial pneumonia was confirmed by a blinded clinical-events committee.

Measurements And Main Results: During a mean follow-up of 16 months, 116 participants (2.2%) developed at least one episode of bacterial pneumonia. Patients randomized to receive episodic antiretroviral therapy were significantly more likely to develop pneumonia than patients randomized to receive continuous antiretroviral therapy (hazard ratio, 1.55; 95% confidence interval, 1.07-2.25; P = 0.02). Cigarette smoking was a major risk factor: Current-smokers had more than an 80% higher risk of pneumonia compared with never-smokers (hazard ratio, 1.82; 95% confidence interval, 1.09-3.04; P = 0.02). Participants who were on continuous HIV treatment and were current smokers were three times more likely to develop bacterial pneumonia than nonsmokers. Current smoking status was significant, but a past history of smoking was not.

Conclusions: Bacterial pneumonia is a major source of morbidity, even for persons on potent antiretroviral therapy, including those with high CD4 cells. Efforts to reduce this illness should stress the importance of uninterrupted antiretroviral therapy and attainment and/or maintenance of nonsmoking status.
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http://dx.doi.org/10.1164/rccm.200804-617OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542436PMC
September 2008

The impact of episodic CD4 cell count-guided antiretroviral therapy on quality of life.

J Acquir Immune Defic Syndr 2008 Feb;47(2):185-93

Denver Public Health Department and the Department of Medicine, University of Colorado Health Sciences Center, Denver, CO, USA.

Objective: To evaluate the effect of episodic antiretroviral therapy on quality of life (QOL).

Design: This was a substudy of the Strategies of Management of Antiretroviral Therapy study, in which patients were randomized to continuous versus CD4 cell count-guided episodic antiretroviral therapy. QOL assessments included an analog scale for current health and the Short-Form 12 Item Survey, a standard abbreviated QOL instrument.

Results: A total of 1225 patients had QOL assessments over a mean follow-up time of 2.4 years. Most (76%) were on antiretroviral therapy at enrollment; the median CD4 lymphocyte count was 575 (interquartile range: 455 to 784) cells/mm3; and mean current health was 75 on a scale from 0 to 100, and 50% reported very good or excellent general health. Through follow-up, whenever QOL outcomes differed, the results were inferior among patients in the episodic therapy group compared with the continuous therapy group (current health, Physical Health Component Score [both P = 0.05], general health perceptions, physical functioning, and energy [all P = 0.03]). HIV disease progression (opportunistic disease or death) was more common in the episodic therapy arm and was preceded by marked declines in QOL, but excluding participants with disease progression had minimal effect on QOL comparisons.

Conclusion: CD4 count-guided episodic use of antiretroviral therapy resulted in inferior QOL compared with continuous therapy.
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http://dx.doi.org/10.1097/QAI.0b013e31815acaa4DOI Listing
February 2008
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