No neurocognitive advantage for immediate antiretroviral treatment in adults with greater than 500 CD4+ T-cell counts

OBJECTIVE: To compare the effect of immediate versus deferred antiretroviral treatment (ART) on neuropsychological test performance in treatment-naive HIV-positive adults with more than 500 CD4 cells/µl. DESIGN: Randomized trial. METHODS: The START parent study randomized participants to commence immediate versus deferred ART until CD4 less than 350 cells/µl. The START Neurology substudy used eight neuropsychological tests, at baseline, months 4, 8, 12 and annually, to compare groups for changes in test performance. Test results were internally standardized to z-scores. The primary outcome was the average of the eight test z-scores (QNPZ-8). Mean changes in QNPZ-8 from baseline were compared by intent-to-treat using longitudinal mixed models. Changes from baseline to specific time points were compared using ANCOVA models. RESULTS: The 592 participants had a median age of 34 years; median baseline CD4 count was 629 cells/µl; the mean follow-up was 3.4 years. ART was used for 94 and 32% of accrued person-years in the immediate and deferred groups, respectively. There was no difference between the immediate and deferred ART groups in QNPZ-8 change through follow-up [-0.018 (95% CI -0.062 to 0.027, P = 0.44)], or at any visit. However, QNPZ-8 scores increased in both arms during the first year, by 0.22 and 0.24, respectively (P < 0.001 for increase from baseline). CONCLUSION: We observed substantial improvement in neurocognitive test performance during the first year in both study arms, underlining the importance of using a control group in studies assessing neurocognitive performance over time. Immediate ART neither benefitted nor harmed neurocognitive performance in individuals with CD4 cell counts above 500 cells/µl

No neurocognitive advantage for immediate antiretroviral treatment in adults with greater than 500 CD4+ T-cell counts.

OBJECTIVE: To compare the effect of immediate versus deferred antiretroviral treatment (ART) on neuropsychological test performance in treatment-naive HIV-positive adults with more than 500 CD4 cells/µl. DESIGN: Randomized trial. METHODS: The START parent study randomized participants to commence immediate versus deferred ART until CD4 less than 350 cells/µl. The START Neurology substudy used eight neuropsychological tests, at baseline, months 4, 8, 12 and annually, to compare groups for changes in test performance. Test results were internally standardized to z-scores. The primary outcome was the average of the eight test z-scores (QNPZ-8). Mean changes in QNPZ-8 from baseline were compared by intent-to-treat using longitudinal mixed models. Changes from baseline to specific time points were compared using ANCOVA models. RESULTS: The 592 participants had a median age of 34 years; median baseline CD4 count was 629 cells/µl; the mean follow-up was 3.4 years. ART was used for 94 and 32% of accrued person-years in the immediate and deferred groups, respectively. There was no difference between the immediate and deferred ART groups in QNPZ-8 change through follow-up [-0.018 (95% CI -0.062 to 0.027, P = 0.44)], or at any visit. However, QNPZ-8 scores increased in both arms during the first year, by 0.22 and 0.24, respectively (P < 0.001 for increase from baseline). CONCLUSION: We observed substantial improvement in neurocognitive test performance during the first year in both study arms, underlining the importance of using a control group in studies assessing neurocognitive performance over time. Immediate ART neither benefitted nor harmed neurocognitive performance in individuals with CD4 cell counts above 500 cells/µl.

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

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. Cryptococcus 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.

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.

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

Low prevalence of neurocognitive impairment in early diagnosed and managed HIV-infected persons.

OBJECTIVE: To describe the prevalence of neurocognitive impairment (NCI) among early diagnosed and managed HIV-infected persons (HIV+) compared to HIV-negative controls. METHODS: We performed a cross-sectional study among 200 HIV+ and 50 matched HIV-uninfected (HIV-) military beneficiaries. HIV+ patients were categorized as earlier (<6 years of HIV, no AIDS-defining conditions, and CD4 nadir >200 cells/mm(3)) or later stage patients (n = 100 in each group); both groups were diagnosed early and had access to care. NCI was diagnosed using a comprehensive battery of standardized neuropsychological tests. RESULTS: HIV+ patients had a median age of 36 years, 91% were seroconverters (median window of 1.2 years), had a median duration of HIV of 5 years, had a CD4 nadir of 319, had current CD4 of 546 cells/mm(3), and 64% were on highly active antiretroviral therapy (initiated 1.3 years after diagnosis at a median CD4 of 333 cells/mm(3)). NCI was diagnosed among 38 (19%, 95% confidence interval 14%-25%) HIV+ patients, with a similar prevalence of NCI among earlier and later stage patients (18% vs 20%, p = 0.72). The prevalence of NCI among HIV+ patients was similar to HIV- patients. CONCLUSIONS: HIV+ patients diagnosed and managed early during the course of HIV infection had a low prevalence of NCI, comparable to matched HIV-uninfected persons. Early recognition and management of HIV infection may be important in limiting neurocognitive impairment.

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

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 (ßCTX) 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 ßCTX 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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.