A Novel Score to Predict Esophageal Varices in Patients with Compensated Advanced Chronic Liver Disease.

BACKGROUND AND AIMS: Several criteria have been described to noninvasively predict the presence of high-risk esophageal varices in patients with compensated advanced chronic liver disease (cACLD). However, a recent study showed that treatment with ß blockers could increase decompensation-free survival in patients with clinically significant portal hypertension, thereby making it important to predict the presence of any esophageal varices. We aimed to develop a simple scoring system to predict any esophageal varices. METHODS: We retrospectively reviewed patients who had vibration-controlled transient elastography (VCTE) at Cook County Hospital, Chicago, USA. Patients with cACLD and liver stiffness measurement (LSM) ≥ 10 kPa with esophagogastroduodenoscopy performed within one year of VCTE were analyzed. We generated a novel score to predict esophageal varices, using the beta coefficient of predictive variables. The score was validated in an external cohort at the University of Iowa Hospital, USA. RESULTS: There were 372 patients in the development cohort and 200 patients in the validation cohort. LSM, platelet count, and albumin were identified as predictors of esophageal varices and were included for generating the Cook County score as "platelet count * - 0.0155872 + VCTE score * 0.0387052 + albumin * - 0.8549209." The area under receiver operating curve for our score was 0.86 for any varices and 0.85 for high risk varices and avoided more endoscopies than the expanded Baveno VI criteria while maintaining a very low miss rate (negative predictive value > 99%). CONCLUSION: We propose a new, highly accurate, and easy-to-use scoring system to predict the presence of not only high-risk but any esophageal varices in patients with cACLD.

Retracted: Electronic Clinical Decision Support Intervention to Increase Hepatitis C Screening and Linkage to Care Among Baby Boomers in Urban Safety Net Health Systems.

The article entitled, "Electronic Clinical Decision Support Intervention to Increase Hepatitis C Screening and Linkage to Care Among Baby Boomers in Urban Safety Net Health Systems," by Armstrong et al., published online ahead of print (2019 Oct 8) in Population Health Management [doi: 10.1089/pop.2019.0105], requires a retraction due to duplicate publication in the Journal of Community Medicine & Health Education (JCMHE) in February of 2019, and then in Population Health Management in October of 2019. As it is against the standard protocols of peer review to publish original research in two different journals, Population Health Management is officially retracting the article from its literature. Population Health Management is dedicated to adhering to the policies and best practices of scientific publishing and the community it serves.

Steatosis Rates by Liver Biopsy and Transient Elastography With Controlled Attenuation Parameter in Clinical Experience of Hepatitis C Virus (HCV) and Human Immunodeficiency Virus/HCV Coinfection in a Large US Hepatitis Clinic.

BACKGROUND: Steatosis contributes to liver fibrosis in hepatitis C virus (HCV) and human immunodeficiency virus (HIV)/HCV coinfection. Liver biopsy (LB) is the reference standard for grading steatosis and staging fibrosis, yet recent advances in noninvasive modalities have largely supplanted LB, which may limit recognition of steatosis. We evaluated steatosis rates by LB and transient elastography (TE) with controlled attenuation parameter (CAP) among HCV-infected and HIV/HCV-coinfected patients in a US clinic. METHODS: Patients with chronic HCV infection during pretreatment evaluation by LB (n = 421; December 2001 through May 2014) and TE with CAP (n = 1157; May 2016 through May 2017) were included. Fibrosis and steatosis rates by LB and TE with CAP were stratified by HCV versus HIV/HCV coinfection status. RESULTS: Steatosis was not reported in 26.1% of LBs. Moderate to severe steatosis (grade ≥S2) was detected more often with CAP than with LB (in 24.0% vs 11.4% of patients, respectively). Median CAP values were higher in patients with HCV monoinfection than in those with coinfection (230 vs 215.5 dB/m, respectively; P < .001). With TE, the rate of advanced fibrosis (values F3-F4) was higher in HCV monoinfection than in coinfection (25.9% vs 14.8%, respectively; P <.001). With both LB and TE, advanced fibrosis (F3-F4) was significantly associated with moderate to severe steatosis (S2-S3) in HCV monoinfection compared with HIV/HCV coinfection (33.3% vs 4.4%, respectively for LB [P = 0.003] and 36.0% vs 29.0% for TE [P = 0.008]). CONCLUSIONS: In patients with chronic HCV undergoing liver fibrosis staging, steatosis was detected more often with CAP than LB, with median CAP values higher in HCV monoinfection than HIV/HCV coinfection. Steatosis severity may be increasing in the modern HCV treatment era.

Neopterin is associated with hippocampal subfield volumes and cognition in HIV.

OBJECTIVE: HIV infection sets off an immediate immune response and inflammatory cascade that can lead to neuronal injury and cognitive impairment, but the relationship between immune markers, regional brain volumes, and cognition remains understudied in HIV-infected adults. METHODS: Cross-sectional associations were examined between serum immune markers of activation (neopterin) and inflammation (interleukin [IL]-1ß, IL-6, tumor necrosis factor alpha, and C-reactive protein) with regional brain volumes (cortical, subcortical, total gray matter, hippocampus, and subfields) and cognition in 66 HIV-infected, virally suppressed, adults who underwent 3.0-T MRI as part of the Research Core of the Rush Center of Excellence on Disparities in HIV and Aging. Immune markers were assayed from frozen plasma, values were entered into linear regression models as predictors of regional brain volumes, and interactive effects of immune response and regional brain volumes on cognition were examined. RESULTS: No inflammatory marker was associated with any regional brain volume. Higher neopterin level was associated with lower total hippocampal, presubiculum, and cornu ammonis (CA) subfield volumes. Higher neopterin level and lower total hippocampal volume were independently associated with lower episodic memory, and neopterin level fully mediated the effect of hippocampal atrophy on episodic memory. Higher neopterin levels were associated with lower presubiculum, CA1, and CA4/dentate volumes and lower semantic memory, working memory, and global cognition. CONCLUSION: Immune activation in response to HIV infection, measured by neopterin, has a deleterious and targeted effect on regional brain structure, which can be visualized with clinically available MRI measures of hippocampus and its subfields, and this effect is associated with lower cognitive function.

Effects of Fish Oil on HIV-Related Inflammation and Markers of Immunosenescence: A Randomized Clinical Trial.

OBJECTIVE: To explore the safety and efficacy of fish oil to modulate parameters of inflammation and immunosenescence in HIV-infected older adults. DESIGN: This study uses a randomized, controlled, double-blind clinical trial. SETTING: The study was conducted in an outpatient HIV/AIDS clinic in a large urban Midwestern city in the United States. SUBJECTS: A total of 37 clinically stable HIV-infected adults between the ages of 40 and 70 years of age participated. INTERVENTIONS: Fish oil 1.6 g/day was administered for 12 weeks or placebo. OUTCOME MEASURES: Inflammatory cytokine production, surface markers of immunosenescence, and adverse events were measured. RESULTS: After 12 weeks of supplementation, there were no significant differences between the treatment and control groups on any measures of inflammation or immunosenescence in both CD4+ and CD8+ T lymphocytes. More participants in the treatment group reported adverse gastrointestinal events compared with the control group. CONCLUSIONS: A 12-week supplementation regimen of 1.6 g/day of fish oil did not favorably modulate parameters of inflammation or immune senescence in HIV-infected adults. Future studies should test agents that directly target mechanisms that underlie HIV-related inflammation to determine whether reducing inflammation can reverse immunosenescence.

Vitamin D deficiency and periodontal clinical attachment loss in HIV-seropositive women: A secondary analysis conducted in the Women's Interagency HIV Study (WIHS).

OBJECTIVE: The aim of this study was to test a hypothesized positive association between low vitamin D (VitD) serum levels and the severity of periodontal disease in women with HIV infection. STUDY DESIGN: This was a cross-sectional secondary analysis of data from an oral substudy conducted within the Chicago site of the Women's Interagency HIV Study. Serum VitD levels and clinical attachment loss (CAL) measurements were available for 74 women with HIV infection. VitD levels were treated as both continuous and categorical variables in bivariate and multivariate analyses. Mean clinical attachment loss (mCAL) was determined for each subject by obtaining the averages of measurements taken at 4 sites in each measured tooth. RESULTS: Average age of study participants (n = 74) was 39.6 years (standard deviation 7.2), and the majority were African Americans (70.3%) with VitD deficiency (58.1%). VitD deficiency was positively associated with higher mCAL (P = .012). After adjustment for race, age, smoking, and HIV viral load, an association was found between VitD deficiency and mCAL (Beta 0.438; P = .036). CONCLUSIONS: We identified a previously unreported association between VitD deficiency and mCAL in women with HIV infection. Larger and more inclusive, multisite, longitudinal studies are warranted to investigate whether these findings can be generalized to all individuals with HIV infection in the current treatment era and to determine causality.

Sofosbuvir and Velpatasvir for the Treatment of Hepatitis C Virus in Patients Coinfected With Human Immunodeficiency Virus Type 1: An Open-Label, Phase 3 Study.

BACKGROUND: A safe, simple, effective, and pan-genotypic regimen to treat hepatitis C virus (HCV) infection in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains a medical need. We assessed the efficacy and safety of the NS5B polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir for HCV in patients coinfected with HIV-1. METHODS: This phase 3, open-label, single-arm study at 17 sites in the United States enrolled patients with HCV of any genotype and HIV-1 coinfection, including those with compensated cirrhosis. All patients received sofosbuvir-velpatasvir once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). Efficacy and safety were assessed in all patients receiving at least 1 dose of treatment. RESULTS: Of 106 patients, 91 (86%) were men, 48 (45%) were black, and 19 (18%) had cirrhosis. SVR12 was achieved by 101 of 106 (95% [95% confidence interval {CI}, 89%-99%]) patients: 74 of 78 (95% [95% CI, 87%-99%]) with genotype 1; all 11 (100% [95% CI, 72%-100%]) with genotype 2; 11 of 12 (92% [95% CI, 62%-100%]) with genotype 3; and all 5 (100% [95% CI, 48%-100%]) with genotype 4. All 19 patients with cirrhosis had SVR12. Two patients relapsed, 2 were lost to follow-up, and 1 withdrew consent. Two discontinued treatment due to adverse events and 2 had serious adverse events. The most common adverse events were fatigue (25%), headache (13%), upper respiratory tract infection (8%), and arthralgia (8%). CONCLUSIONS: Sofosbuvir-velpatasvir for 12 weeks was safe and provided high rates of SVR12 in patients coinfected with HCV and HIV-1. CLINICAL TRIALS REGISTRATION: NCT02480712.

TURQUOISE-I Part 1b: Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with Ribavirin for Hepatitis C Virus Infection in HIV-1 Coinfected Patients on Darunavir.

Background: Ombitasvir/paritaprevir/ritonavir with dasabuvir (OBV/PTV/r + DSV) ± ribavirin (RBV) is approved for hepatitis C virus (HCV) genotype 1 (GT1) treatment in HIV-1 coinfected patients. In healthy controls, coadministration of OBV/PTV/r + DSV + darunavir (DRV) lowered DRV trough concentration (Ctrough) levels. To assess the clinical significance of this change, TURQUOISE-I, Part 1b, evaluated the efficacy and safety of OBV/PTV/r + DSV + RBV in coinfected patients on stable, DRV-containing antiretroviral therapy (ART). Methods: Patients were HCV treatment-naive or interferon-experienced, had CD4+ lymphocyte count ≥200 cells/µL or ≥14%, and plasma HIV-1 RNA suppression on once-daily (QD) DRV-containing ART at screening. Patients were randomized to maintain DRV 800 mg QD or switch to twice-daily (BID) DRV 600 mg; all received OBV/PTV/r + DSV + RBV for 12 weeks. Results: Twenty-two patients were enrolled and achieved SVR12. No adverse events led to discontinuation. Coadministration had minimal impact on DRV maximum observed plasma concentration and area under the curve; DRV Ctrough levels were slightly lower with DRV QD and BID. No patient experienced plasma HIV-1 RNA >200 copies/mL during treatment. Conclusions: HCV GT1/HIV-1 coinfected patients on stable DRV-containing ART achieved 100% SVR12 while maintaining plasma HIV-1 RNA suppression. Despite DRV exposure changes, episodes of intermittent HIV-1 viremia were infrequent.

Loneliness in Older Black Adults with Human Immunodeficiency Virus Is Associated with Poorer Cognition.

BACKGROUND: The human immunodeficiency virus (HIV) is associated with cognitive impairment, and loneliness is associated with cognitive decline in old age. Older Black adults with HIV may be at particular risk of loneliness due to stigma and lack of social resources. OBJECTIVE: We tested the hypotheses that (1) older Black adults with HIV would show greater loneliness than older White adults with HIV, and (2) greater loneliness among older Black adults with HIV would be associated with poorer cognitive function. METHODS: A total of 370 participants (177 with HIV, 193 without HIV; mean age 58.8 years, standard deviation 6.2 years; mean education 13.4 years, standard deviation 2.9 years; 73.9% male, 68.9% Black) in a community-based cross-sectional study of the Rush Center of Excellence on Disparities in HIV and Aging (CEDHA) completed a 5-item self-report scale used to measure emotional loneliness and a battery of cognitive measures. RESULTS: Contrary to our expectations, older Black adults indicated less overall loneliness than White adults (ß = -0.3893, SE = 0.1466, p = 0.0087) in models controlling for the effects of age, education, sex, global cognition, and income. However, in models with cognitive function as the outcome, an interaction between race and loneliness was observed, such that older Black adults who indicated greater loneliness showed poorer cognitive function relative to White adults (ß = -0.2736, SE = 0.1138, p = 0.0174). CONCLUSION: Older Black adults with HIV reported less loneliness than older White adults; however, the inverse association between loneliness and cognitive function was stronger in Black than White older adults. Additional work is needed to elucidate the mechanisms underlying this interaction.

Association of cognitive activity and neurocognitive function in blacks and whites with HIV.

OBJECTIVE: Older persons with HIV are at risk for impaired cognition, yet there is limited information on modifiable factors associated with neurocognitive function in this group. DESIGN: This is a cross-sectional observational study of cognitive activities and neurocognitive function. METHODS: We examined the relation between frequency of cognitive activity and current neurocognitive performance in 176 older persons with HIV [70% African American, 76% men; mean age = 58.7 (SD = 5.5); mean education = 13.2 (SD = 2.8)]. RESULTS: In linear regression models adjusted for demographic variables, we found that higher frequency of cognitive activity was associated with better cognition in global cognition, semantic memory, and perceptual speed. Subsequent models that examined the role of race demonstrated that the association was significant only among Blacks for global cognition, episodic memory, working memory, and perceptual speed (interaction of cognitive activity by race: Estimate range = 0.38-0.55; all P < 0.05). CONCLUSION: Greater frequency of cognitive activity is associated with better neurocognitive function in older persons with HIV, particularly older Blacks. Longitudinal studies are needed to assess the relation of cognitive activity to change in neurocognitive function in older persons with HIV.

Short Communication: SCD14 and SCD163 Levels Are Correlated with VACS Index Scores: Initial Data from the Blunted Immune Recovery in CORE Patients with HIV (BIRCH) Cohort.

The relationship between markers of monocyte/macrophage activation (sCD14 and sCD163) and components of the Veterans Aging Cohort Study (VACS) score, which predict mortality in patients with HIV, in immunologic nonresponders (INRs) is not defined. HIV(+) subjects with >12 months of continuous virologic suppression and persistent CD4 <250 cells/mm(3) were enrolled at the CORE Center, Chicago. Subjects had a single visit where history was taken and blood drawn. ELISA assays for sCD14 and sC163 were performed at Blood Systems, CA. Descriptive statistics were performed using SAS. We enrolled 43 subjects with persistent CD4 <250 after a median of 32 months of continuous viral suppression. We found elevated markers of monocyte/macrophage activation; sCD14 and sCD163 correlated with higher VACS scores as well as hepatitis C virus (HCV) coinfection and FIB-4 score, components of the VACS index. In this cohort of immunologic nonresponders, there was a significant correlation between markers of monocyte/macrophage activation and the VACS score. Among components of the VACS index, we did not find a significant association between HCV coinfection and sCD14; however, there was a significant association between HCV coinfection and sCD163.

Acupuncture to Reduce HIV-Associated Inflammation.

Background. HIV infection is associated with systemic inflammation that can increase risk for cardiovascular events. Acupuncture has been shown to have immunomodulatory effects and to improve symptoms in persons with inflammatory conditions. Objective. To test the anti-inflammatory effects of an acupuncture protocol that targets the cholinergic anti-inflammatory pathway (CAIP), a neural mechanism whose activation has been shown to reduce the release of proinflammatory cytokines, in persons with HIV-associated inflammation. Design, Setting, Participants, and Interventions. Double-blind, placebo-controlled clinical trial conducted in an outpatient clinic located in a medically underserved urban neighborhood. Twenty-five clinically-stable HIV-infected persons on antiretroviral therapy were randomized to receive once weekly CAIP-based acupuncture or sham acupuncture. Main Outcome Measures. Outcomes included plasma concentrations of high sensitivity C-reactive protein and D-dimer and fasting lipids. Results. Twenty-five participants completed the protocol (treatment group n = 12, control group n = 13). No adverse events related to the acupuncture protocol were observed. Compared to baseline values, the two groups did not significantly differ in any outcome measures at the end of the acupuncture protocol. Conclusions. CAIP-based acupuncture did not favorably modulate inflammatory or lipid parameters. Additional studies are warranted of CAIP-based protocols of different frequencies/durations.

Risk of breast cancer with CXCR4-using HIV defined by V3 loop sequencing.

OBJECTIVE: Evaluate the risk of female breast cancer associated with HIV-CXCR4 (X4) tropism as determined by various genotypic measures. METHODS: A breast cancer case-control study, with pairwise comparisons of tropism determination methods, was conducted. From the Women's Interagency HIV Study repository, one stored plasma specimen was selected from 25 HIV-infected cases near the breast cancer diagnosis date and 75 HIV-infected control women matched for age and calendar date. HIV-gp120 V3 sequences were derived by Sanger population sequencing (PS) and 454-pyro deep sequencing (DS). Sequencing-based HIV-X4 tropism was defined using the geno2pheno algorithm, with both high-stringency DS [false-positive rate (3.5) and 2% X4 cutoff], and lower stringency DS (false-positive rate, 5.75 and 15% X4 cutoff). Concordance of tropism results by PS, DS, and previously performed phenotyping was assessed with kappa (κ) statistics. Case-control comparisons used exact P values and conditional logistic regression. RESULTS: In 74 women (19 cases, 55 controls) with complete results, prevalence of HIV-X4 by PS was 5% in cases vs 29% in controls (P = 0.06; odds ratio, 0.14; confidence interval: 0.003 to 1.03). Smaller case-control prevalence differences were found with high-stringency DS (21% vs 36%, P = 0.32), lower stringency DS (16% vs 35%, P = 0.18), and phenotyping (11% vs 31%, P = 0.10). HIV-X4 tropism concordance was best between PS and lower stringency DS (93%, κ = 0.83). Other pairwise concordances were 82%-92% (κ = 0.56-0.81). Concordance was similar among cases and controls. CONCLUSIONS: HIV-X4 defined by population sequencing (PS) had good agreement with lower stringency DS and was significantly associated with lower odds of breast cancer.

Relationship of vitamin D, HIV, HIV treatment, and lipid levels in the Women's Interagency HIV Study of HIV-infected and uninfected women in the United States.

Relationships between vitamin D, lipids, HIV infection, and HIV treatment (±antiretroviral therapy [ART]) were investigated with Women's Interagency HIV Study data (n = 1758 middle-aged women) using multivariable regression. Sixty-three percent of women had vitamin D deficiency. Median 25-hydroxyvitamin D (25-OH vitamin D) was highest in HIV-infected + ART-treated women (17 ng/mL; P < .001) and was the same in HIV-uninfected or HIV-infected women without ART (14 ng/mL). Vitamin D levels were lower if efavirenz (EFV) was included in ART (15 versus 19 ng/mL; P < .001). The most common lipid abnormality was high triglycerides (≥200 mg/dL) in HIV-infected + ART-treated women (13% versus 7% of HIV-infected without ART and 5% of HIV-uninfected; P < .001), with a positive relationship between 25-OH vitamin D and triglycerides (95% confidence interval 0.32-1.69; P < .01). No relationships between 25-OH vitamin D and cholesterol were detected. Vitamin D deficiency is common irrespective of HIV status but influenced by HIV treatment. Similarly, vitamin D levels were positively related to triglycerides only in ART-treated HIV-infected women and unrelated to cholesterol.

Virologic response, early HIV-1 decay, and maraviroc pharmacokinetics with the nucleos(t)ide-free regimen of maraviroc plus darunavir/ritonavir in a pilot study.

OBJECTIVE: To address the need for nucleos(t)ide reverse transcriptase inhibitor (NRTI)-sparing regimens, we explored the virologic and pharmacokinetic characteristics of maraviroc plus ritonavir-boosted darunavir in a single-arm, open-label, 96-week study. METHODS: Twenty-four antiretroviral-naive R5 HIV-1-infected participants received maraviroc 150 mg and darunavir/ritonavir (DRV/r) 800/100 mg (MVC/DRV/r) once daily. The primary outcome was virologic failure (VF) = confirmed viral load (VL) >50 copies per milliliter at week 24 in the modified intent-to-treat population. To determine viral dynamics, participant-specific first- and second-phase empirical Bayes estimates were compared with decay rates from efavirenz (EFV) plus lopinavir/ritonavir, lopinavir/ritonavir plus 2NRTIs, and EFV plus 2NRTIs. Maraviroc plasma concentrations were determined at weeks 2, 4, 12, 24, and 48. RESULTS: Baseline median (Q1, Q3) CD4 count and VL were 455 (299, 607) cells per cubic millimeter and 4.62 (4.18, 4.80) log10 copies per milliliter, respectively. VF occurred in 3 of 24 participants {12.5% [95% confidence interval (CI): 2.7 to 32.4]} at week 24. One of these resuppressed, yielding a week 48 VF rate of 2/24 [8.3% (95% CI: 1.0 to 27.0)]. The week 48 failures were 2 of the 4 participants (50%) with baseline VL >100,000 copies per milliliter. Week 96 VF rate was 2/20 [10% (95% CI: 1.2 to 31.7)]. Phase 1 decay was faster with MVC/DRV/r than reported for ritonavir-boosted lopinavir plus 2NRTIs (P = 0.0063) and similar to EFV-based regimens. Individual maraviroc trough concentrations collected between 20 and 28 hours post dose (n = 59) was 13.7 to 130 ng/mL (Q1, 23.4 ng/mL; Q3, 46.5 ng/mL), and modeled steady-state concentration was 128 ng/mL. CONCLUSIONS: MVC/DRV/r 150/800/100 mg once daily has potential for treatment-naive patients with R5 HIV-1.

Vitamin D and insulin resistance in non-diabetic women's interagency HIV study participants.

We explored the relationship between vitamin D levels and insulin resistance (IR) among 1082 nondiabetic (754 HIV-infected) women enrolled in the Women's Interagency HIV study (WIHS), a large and well-established cohort of HIV infected and uninfected women in the US. Vitamin D levels 20-29 ng/mL were considered insufficient and <20 ng/mL deficient. IR was estimated using the homeostasis model assessment (HOMA) and a clinically significant cut-off ≥2.6 was used for HOMA-IR. In the unadjusted analysis, women who were vitamin D insufficient or deficient were 1.62 (95% CI: 1.01-2.61, p=0.05) and 1.70 (95% CI: 1.11-2.60, p=0.02) times more likely to have HOMA values≥2.6 compared to women with sufficient vitamin D. The association did not remain significant after adjustment for factors associated with IR. Among the 754 HIV-infected women, current PI use (OR 1.61, 95% CI: 1.13-2.28, p=0.008) remained independently associated with HOMA ≥2.6 while vitamin D insufficiency (OR 1.80, 95% CI: 0.99-3.27, p=0.05) was marginally associated with HOMA ≥2.6 after adjustment. Ethnicity, body mass index, smoking status, and hepatitis C status were independently associated with insulin resistance in HIV-infected and uninfected women. We found a marginally significant association between vitamin D insufficiency and insulin resistance among nondiabetic HIV-infected WIHS women.

The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial.

The CCR5 inhibitor maraviroc has been hypothesized to decrease T-cell activation in HIV-infected individuals, but its independent immunologic effects have not been established in a placebo-controlled trial. We randomized 45 HIV-infected subjects with CD4 counts <350 cells per mm(3) and plasma HIV RNA levels <48 copies per mL on antiretroviral therapy (ART) to add maraviroc vs placebo to their regimen for 24 weeks followed by 12 weeks on ART alone. Compared with placebo-treated subjects, maraviroc-treated subjects unexpectedly experienced a greater median increase in % CD38+HLA-DR+ peripheral blood CD8+ T cells at week 24 (+2.2% vs -0.7%, P = .014), and less of a decline in activated CD4+ T cells (P < .001). The % CD38+HLA-DR+ CD4+ and CD8+ T cells increased nearly twofold in rectal tissue (both P < .001), and plasma CC chemokine receptor type 5 (CCR5) ligand (macrophage-inflammatory protein 1ß) levels increased 2.4-fold during maraviroc intensification (P < .001). During maraviroc intensification, plasma lipopolysaccharide declined, whereas sCD14 levels and neutrophils tended to increase in blood and rectal tissue. Although the mechanisms explaining these findings remain unclear, CCR5 ligand-mediated activation of T cells, macrophages, and neutrophils via alternative chemokine receptors should be explored. These results may have relevance for trials of maraviroc for HIV preexposure prophylaxis and graft-versus-host disease. This trial was registered at www.clinicaltrials.gov as #NCT00735072.