What are patients asking and reading online? An analysis of online patient searches for rotator cuff repair.

BACKGROUND: Patients undergoing rotator cuff surgery often search the internet for information regarding the procedure. One popular source, Google, compiles frequently asked questions and links to websites that may provide answers. This study provides an analysis of the most frequently searched questions associated with rotator cuff surgery. We hypothesize that there will be distinct search patterns associated with online queries about rotator cuff surgery that could provide unique insights into patient concerns. METHODS: A set of search terms were entered into Google Web Search using a clean-install Google Chrome browser. Frequently associated questions and their webpages were extracted to a database via a data mining extension. Questions were categorized by topics relevant for rotator cuff arthroscopy. Websites were categorized by source and scored for quality using the JAMA Benchmark Criteria. Pearson's χ2 tests were used to analyze nominal data. Student t tests were performed to compare JAMA Benchmark Scores. RESULTS: Of the 595 questions generated from the initial search, 372 unique questions associated with 293 websites were extracted and categorized. The most popular question topics were activities/restrictions (20.7%), pain (18.8%), and indications/management (13.2%). The 2 most common websites searched were academic (35.2%) and medical practice (27.4%). Commercial websites were significantly more likely to be associated with questions about cost (57.1% of all cost questions, P = .01), anatomy/function (62.5%, P = .001), and evaluation of surgery (47.6%, P < .001). Academic websites were more likely to be associated with questions about technical details of surgery (58.1%, P < .001). Medical practice and social media websites were more likely associated with activities/restrictions (48.1%, P < .001, and 15.6%, P < .001, respectively). Government websites were more likely associated with timeline of recovery (12.8%, P = .01). On a scale of 0-4, commercial and academic websites had the highest JAMA scores (3.06 and 2.39, respectively). CONCLUSION: Patients seeking information regarding rotator cuff repair primarily use the Google search engine to ask questions regarding postoperative activity and restrictions, followed by pain, indications, and management. Academic websites, which were associated with technical details of surgery, and medical practice websites, which were associated with activities/restrictions, were the 2 most commonly searched resources. These results emphasize the need for orthopedic surgeons to provide detailed and informative instructions to patients undergoing rotator cuff repair, especially in the postoperative setting.

Adipokines, Weight Gain and Metabolic and Inflammatory Markers After Antiretroviral Therapy Initiation: AIDS Clinical Trials Group (ACTG) A5260s.

BACKGROUND: The adipokines leptin and adiponectin, produced primarily by adipose tissue, have diverse endocrine and immunologic effects, and circulating levels reflect adipocyte lipid content, local inflammation, and tissue composition. We assessed relationships between changes in regional fat depots, leptin and adiponectin levels, and metabolic and inflammatory markers over 96 weeks in the AIDS Clinical Trials Group (ACTG) A5260s metabolic substudy of the A5257 randomized trial of tenofovir disoproxil fumarate/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir among treatment-naive persons with human immunodeficiency virus (PWH). METHODS: Fat depots were measured using dual-energy absorptiometry and abdominal computed tomographic imaging at treatment initiation and 96 weeks later. Serum leptin and adiponectin, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hsCRP) were measured at the same timepoints. Multivariable regression models assessed relationships between fat depots, adipokines, HOMA-IR, and hsCRP at week 96. RESULTS: Two hundred thirty-four participants maintained viral suppression through 96 weeks (90% male, 29% black, median age 36 years). Serum leptin increased over 96 weeks (mean change 22%) while adiponectin did not (mean change 1%), which did not differ by study arm. Greater trunk, limb, and abdominal subcutaneous and visceral fat were associated with higher HOMA-IR and hsCRP at 96 weeks, but serum leptin level was a stronger determinant of these endpoints using a mediation model approach. A similar mediating effect was not observed for adiponectin. CONCLUSIONS: Higher circulating leptin is associated with greater HOMA-IR and hsCRP independent of fat depot size, suggesting that greater adipocyte lipid content may contribute to impaired glucose tolerance and systemic inflammation among PWH starting antiretroviral therapy.

Low incidence and prevalence of hepatitis C in two cohorts of HIV pre-exposure prophylaxis adherence interventions in men who have sex with men in Southern California.

HIV pre-exposure prophylaxis (PrEP) has been associated with incident hepatitis C virus (HCV) infection in men who have sex with men (MSM) due to decreased condom use. We examined rates of HCV among MSM and transgender women at high-risk of HIV on PrEP in Southern California using data from two trials (NCT01761643 and NCT01781806). Five of 599 participants (0.84%, 95% CI, 0.27-1.93) had HCV antibodies detected at entry. Factors associated with HCV seropositivity included being older (p = .002) and lower education level (p < .001). HCV-positive participants had no reported cases of sexually transmitted infection (rectal, urethral or pharyngeal gonorrhoea and/or chlamydia) at entry while HCV-negative participants had a prevalence of 18% (95% CI, 15%-21%). There were no significant differences in substance use and sexual risk behaviour between HCV-positive and HCV-negative participants 1-3 months prior to entry. Among early PrEP adopters, incident HCV did not occur despite ongoing condomless intercourse. Screening intervals for HCV in MSM on PrEP should be led by a risk behaviour assessment.

Gut microbiome in people living with HIV is associated with impaired thiamine and folate syntheses.

People living with HIV have a high incidence of cardiovascular and neurological diseases as comorbid disorders that are commonly linked to inflammation. While microbial translocation can augment inflammation during HIV infection, functional microbiome shifts that may increase pro-inflammatory responses have not been fully characterized. In addition, defining HIV-induced microbiome changes has been complicated by high variability among individuals. Here we conducted functional annotation of previously-published 16S ribosomal RNA gene sequences of 305 HIV positive and 249 negative individuals, with adjustment for geographic region, sex, sexual behavior, and age. Metagenome profiles were inferred from these individuals' 16S data. HIV infection was associated with impaired microbial vitamin B synthesis; around half of the gene families in thiamine and folate biosynthesis pathways were significantly less abundant in the HIV positive group than the negative control. These results are consistent with the high prevalence of thiamine and folate deficiencies in HIV infections. These HIV-induced microbiota shifts have the potential to influence cardiovascular and neurocognitive diseases, given the documented associations between B-vitamin deficiencies, inflammation, and these diseases. We also observed that most essential amino acid biosynthesis pathways were downregulated in the microbiome of HIV-infected individuals. Microbial vitamin B and amino acid synthesis pathways were not significantly recovered by antiretroviral treatment when we compared 262 ART positive and 184 ART negative individuals. Our meta-analysis provides a new outlook for understanding vitamin B and amino acid deficiencies in HIV patients, suggesting that interventions for reversing HIV-induced microbiome shifts may aid in lessening the burdens of HIV comorbidities.

Greater Levels of Self-Reported Adherence to Pre-Exposure Prophylaxis (PrEP) are Associated with Increased Condomless Sex Among Men Who Have Sex with Men.

The effectiveness of pre-exposure prophylaxis (PrEP) against HIV acquisition depends on treatment adherence; however, within-person associations between levels of PrEP adherence and engagement in condomless sex have not been well studied. In the context of a demonstration project, 372 men who have sex with men received once-daily PrEP and completed six study visits over 48 weeks. Two-part growth mixture modeling was used to examine the longitudinal trajectory of condomless anal intercourse (CAI) and self-reports of PrEP adherence, controlling for relevant covariates. Over time, greater PrEP adherence was contemporaneously associated with both a higher likelihood of engaging in any CAI and with a greater number of CAI acts. Substance use was also associated with a higher likelihood of engaging in CAI. Contemporaneous associations between self-reported PrEP adherence and CAI suggest that adherence behaviors may be motivated by the desire to mitigate risk of HIV infection; however, exact directionality is unknown.

RESUMEN: La eficacia de la profilaxis Pre-exposición (PrEP) contra la adquisición del VIH depende de la adherencia al tratamiento; sin embargo, las asociaciones dentro de la persona entre los niveles de adherencia a PrEP y la participación en el sexo sin condón no han sido bien estudiadas. En un proyecto de demostración, 372 hombres que tienen relaciones sexuales con hombres recibieron PrEP diariamente y completaron seis visitas de estudio durante 48 semanas. El modelado de mezclas de crecimiento en dos partes se utilizó para examinar la trayectoria longitudinal de las relaciones sexuales anales sin condonación (CAI) y los autoinformes de adherencia a PrEP, controlando las covariables pertinentes. Con el tiempo, una mayor adherencia a PrEP se asoció a la misma vez con una mayor probabilidad de participar en cualquier CAI y tambien con un mayor número de CAI. El consumo de sustancias también se asoció con una mayor probabilidad de participar en CAI. Las asociaciones contemporáneas entre la adherencia a PrEP autoinformada y CAI sugieren que los comportamientos de adherencia pueden estar motivados por el deseo de mitigar el riesgo de infección por el VIH; sin embargo, se desconoce la direccionalidad exacta.

A Randomized, Double-blinded, Placebo-controlled Trial of Sitagliptin for Reducing Inflammation and Immune Activation in Treated and Suppressed Human Immunodeficiency Virus Infection.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have pleotropic anti-inflammatory and immune regulatory effects in addition to glucoregulation. We evaluated inflammation and immune markers in suppressed human immunodeficiency virus (HIV) infection during treatment with the DPP-4 inhibitor sitagliptin. METHODS: Virologically suppressed adults with HIV without diabetes on stable antiretroviral therapy (ART) with ≥100/µL CD4 cells were randomized to 16 weeks of sitagliptin 100 mg/day vs placebo in a multicenter trial. The primary endpoint was the change in plasma soluble CD14 (sCD14) from baseline to week 15-16. RESULTS: Ninety participants were randomized, and 42 from each arm were included in per-protocol analyses. Participants were 45% non-Hispanic white, 38% non-Hispanic black, and 15% Hispanic, with a median age of 51 years; 83% were male; and the median CD4 count was 602 cells/µL. At week 15-16, there was no difference in sCD14 change between the 2 arms (P = .69). Relative to placebo, the sitagliptin arm had 47% greater decline in CXCL10 (95% confidence interval, -57% to -35%) at week 15 (P < .001). There were no significant between-arm differences in other soluble biomarkers, total CD4 and CD8 counts, or markers of lymphocyte or monocyte activation. Sitagliptin was well tolerated. CONCLUSIONS: Sixteen weeks of sitagliptin had no effect on sCD14 levels in virologically suppressed participants with HIV. CXCL10, a chemokine involved in atherogenesis that predicts non-AIDS events during ART, declined markedly with sitagliptin. This suggests that DPP-4 inhibition has the potential to reduce cardiovascular morbidity in treated HIV infection. CLINICAL TRIALS REGISTRATION: NCT01426438.

Trajectories and Predictors of Longitudinal Preexposure Prophylaxis Adherence Among Men Who Have Sex With Men.

Background: Adherence is necessary for efficacy of preexposure prophylaxis (PrEP), and text-messaging methods are promising tools for both adherence assessment and support. Although PrEP adherence is variable, little research has examined patterns of variability or factors associated with longitudinal use. Methods: In the context of a randomized controlled trial of text-messaging versus standard of care for PrEP adherence, 181 men who have sex with men received once-daily tenofovir disoproxil fumarate/emtricitabine and daily adherence texts for 48 weeks. Growth mixture modeling (GMM) was used to identify subgroups of individuals with similar trajectories of text-reported adherence. Between-group differences in pharmacologic measures of adherence (ie, tenofovir diphosphate and emtricitabine triphosphate levels), as well as predictors and study-end attitudes associated with group membership, were examined. Results: GMM identified 4 trajectories of text-reported adherence. Classes with higher text-reported adherence had higher drug concentrations. Younger age and minority race were associated with lower adherence, and individuals in classes with lower adherence had greater baseline levels of depression, substance use concerns, and sexual risk. Differences in study satisfaction were also associated with adherence. Conclusions: This study supports the use of text-reported PrEP adherence. Identifying factors associated with less-than-optimal adherence may aid clinicians in anticipating at-risk patients requiring augmented intervention. Clinical trials registration: NCT01761643.

Randomized Controlled Trial of Daily Text Messages to Support Adherence to Preexposure Prophylaxis in Individuals at Risk for Human Immunodeficiency Virus: The TAPIR Study.

Background: Adherence is critical for efficacy of tenofovir disoproxil fumarate/emtricitabine (FTC) as preexposure prophylaxis (PrEP). Methods: Between February 2013 and February 2016, 398 men who have sex with men and transgender women were randomized 1:1 to receive individualized texting for adherence building (iTAB) or standard care (SoC) for 48 weeks. The primary endpoint was dried blood spot (DBS) tenofovir diphosphate (TFV-DP) concentrations at both week 12 and the last on-drug visit of >719 fmol/punch (ie, adequate adherence). Secondary outcomes included DBS TFV-DP concentrations of >1246 fmol/punch (ie, near-perfect adherence) and plasma FTC >350 ng/mL (consistent with dosing within the past 24 hours). Results: Concentrations >719 fmol/punch of TFV-DP were found in 88.6% of participants at week 12 and 82.5% at week 48. For the primary endpoint, the study arms did not differ (72.0% in iTAB and 69.2% in SoC; P > .05). For the secondary composite endpoint of >1246 fmol/punch the iTAB arm was superior to SoC (33.5% vs 24.8%; P = .06), reaching statistical significance when adjusting for age (odds ratio, 1.56 [95% confidence interval, 1.00-2.42]; P < .05). At week 48, iTAB was superior to SoC for near-perfect adherence (51.0% vs 37.4%; P = .02). At week 12, iTAB was superior to SoC for dosing in past 24 hours by plasma FTC (47.5% vs 33.3%; P = .007), but not at weeks 24, 36, and 48 (all P > .05). Conclusions: Automated text messaging is a low-burden tool that improves durability of near-perfect PrEP adherence. Clinical Trials Registration: NCT01761643.

Substance Use and Adherence to HIV Preexposure Prophylaxis for Men Who Have Sex with Men1.

The effectiveness of oral HIV preexposure prophylaxis (PrEP) strongly depends on maintaining adherence. We investigated the association between substance use and PrEP adherence, as well as incident sexually transmitted infections (STIs) in a high-risk cohort of 394 participants (391 men who have sex with men and 3 transgender women) who were enrolled in a PrEP demonstration project. We assessed baseline and ongoing substance use over a 48-week period for stimulants and nonstimulant substances and for each substance separately. We measured PrEP adherence by using dried blood spots to obtain levels of tenofovir diphosphate. No differences in these levels were found between substance users and nonsubstance users. Baseline stimulant use was strongly associated (odds ratio 3.4; p<0.001) with incident STIs during the study. Thus, PrEP adherence was not decreased by substance use. Because substance users had increased rates of STIs, indicating higher-risk behavior, they might be excellent candidates for PrEP.

Effect of rectal douching/enema on rectal gonorrhoea and chlamydia among a cohort of men who have sex with men on HIV pre-exposure prophylaxis.

OBJECTIVES: Rectal douching/enema (RD) is a common practice among men who have sex with men (MSM) in preparation for sex. RD can break down the rectal mucosal barrier and potentially affect the rectal microbiome. The objective of this study was to understand if RD is associated with acquiring rectal infections (RI) with rectal gonorrhoea (NG) and/or chlamydia (CT). METHODS: From 2013 to 2015, 395 adult HIV-uninfected MSM were enrolled in a randomised controlled study for pre-exposure prophylaxis (PrEP) adherence with routine sexual risk survey and testing. Using data from this cohort, baseline differences by RI were assessed using Pearson's χ² and Wilcoxon-Mann-Whitney test. Association between RD and RI was modelled using multivariable logistic regression adjusted for potential confounders (sexual behaviour, substance use and age) selected a priori. Effect modification by number of male partners and sensitivity analysis to rule out reverse causality were also conducted. RESULTS: Of 395 participants, 261 (66%) performed RD and 133 (33%) had at least one NG/CT RI over 48 weeks. Number of condomless anal receptive sex (med: 4, p<0.001), male partners (med:6, p<0.001) and substance use (any of methamphetamine/hallucinogens/dissociative/poppers) (p<0.001) were associated with increased odds of RI. Controlling for potential confounders, odds of prevalent RI were 3.59 (p<0.001, 95% CI 1.90 to 6.78) and incident RI 3.87 (p=0.001, 95% CI 1.78 to 8.39) when douching weekly or more compared with not douching. MSM with more than six male partners had 5.34 (p=0.002, 95% CI 1.87 to 15.31) increased odds of RI when douching weekly or more compared with not douching. CONCLUSION: Rectal hygiene with RD is a common practice (66%) among HIV-uninfected MSM on PrEP in this study, which increases the odds of acquiring rectal NG and/or CT independent of sexual risk behaviour, substance use and other factors. This suggests interventional approaches targeting rectal hygiene products and practices could reduce sexually transmitted infections.

Randomized Trial of a Health Coaching Intervention to Enhance Retention in Care: California Collaborative Treatment Group 594.

Poor linkage, engagement and retention remain significant barriers in achieving HIV treatment goals in the US. HIV-infected persons entering or re-entering care across three Southern California academic HIV clinics, were randomized (1:1) to an Active, Linkage, Engagement, Retention and Treatment (ALERT) specialist for outreach and health coaching, or standard of care (SOC). The primary outcome of time to loss to follow up (LTFU) was compared using Cox proportional hazards regression modeling. No differences in the median time to LTFU (81.7 for ALERT versus 93.6 weeks for SOC; HR 1.27; p = 0.40), or time to ART initiation was observed (N = 116). Although, ALERT participants demonstrated worsening depressive symptomatology from baseline to week 48 compared to SOC (p = 0.02). The ALERT intervention did not improve engagement and retention in HIV care over SOC. Further studies are needed to determine how best to apply resources to improve retention and engagement.

Practical Review of Recognition and Management of Obesity and Lipohypertrophy in Human Immunodeficiency Virus Infection.

BACKGROUND: Obesity and lipohypertrophy are common in treated human immunodeficiency virus (HIV) infection and contribute to morbidity and mortality among HIV-infected adults on antiretroviral therapy (ART). METHODS: We present a consensus opinion on the diagnosis, clinical consequences, and treatment of excess adiposity in adults with treated HIV infection. RESULTS: Obesity and lipohypertrophy commonly occur among HIV-infected adults on ART and may have overlapping pathophysiologies and/or synergistic metabolic consequences. Traditional, HIV-specific, and ART-specific risk factors all contribute. The metabolic and inflammatory consequences of excess adiposity are critical drivers of non-AIDS events in this population. Although promising treatment strategies exist, further research is needed to better understand the pathophysiology and optimal treatment of obesity and lipohypertrophy in the modern ART era. CONCLUSIONS: Both generalized obesity and lipohypertrophy are prevalent among HIV-infected persons on ART. Aggressive diagnosis and management are key to the prevention and treatment of end-organ disease in this population and critical to the present and future health of HIV-infected persons.

Changes in Markers of T-Cell Senescence and Exhaustion With Atazanavir-, Raltegravir-, and Darunavir-Based Initial Antiviral Therapy: ACTG 5260s.

It is unclear whether differential roles of CD4(+) versus CD8(+) T-cell senescence/exhaustion and effects of antiretroviral therapy (ART) on these processes may contribute to morbidity in treated human immunodeficiency virus type 1 (HIV) infection. In a prospective 96-week trial, 328 HIV-infected ART-naive participants were randomly assigned to receive tenofovir-emtricitabine plus either atazanavir/ritonavir, darunavir/ritonavir, or raltegravir. Markers of CD4(+) T-cell senescence (ie, the percentage of CD28(-)CD57(+) cells among CD4(+) T cells ) and CD4(+)/CD8(+) T-cell exhaustion (ie, the percentage of PD-1(+) cells among CD4(+)/CD8(+) T cells) decreased after ART. There were no changes in markers of CD8(+) T-cell senescence after ART and no differential changes in all markers in ART groups. Senescent CD4(+) and CD8(+) T cells may have differential roles in HIV pathogenesis.

Body Composition Changes After Initiation of Raltegravir or Protease Inhibitors: ACTG A5260s.

BACKGROUND: Fat gain after antiretroviral therapy (ART) occurs, and its association with protease inhibitors (PIs) is unclear. METHODS: Peripheral and central fat depots and lean mass were measured using standardized and centrally read abdominal CT scans and whole-body dual-energy absorptiometry scans over a 96-week period in human immunodeficiency virus (HIV)-infected treatment-naive participants. The patients were randomized to tenofovir-emtricitabine (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or raltegravir (RAL) in ACTG A5260s, a substudy of A5257. Within arm changes were assessed with signed-rank tests. The 96-week percentage changes in fat and lean mass in the 2 PI arms were not different, thus the PI arms were combined and compared to the RAL arm. Associations between baseline biomarkers and changes in body composition were assessed. All analyses used linear regression models. RESULTS: 328 patients were randomized (90% male, 44% white non-Hispanic). The median age was 36 years, HIV-1 RNA 4.6 log10 copies/mL, and CD4 349 cells/µL. Overall, at week 96, increases in limb fat (13.4%), subcutaneous (19.9%) and visceral abdominal fat (25.8%), trunk fat (18%), and lean mass (1.8%) were apparent (P < .001 for changes within each arm). Changes for all fat and lean outcomes were not different between the PI arms or between the RAL and the combined PI arms. Higher baseline HIV-1 RNA levels were associated with greater gains in peripheral and central fat. CONCLUSIONS: In treatment-naive participants initiating ART with TDF/FTC, no differences in lean mass and regional fat were found with RAL when compared with ATV/r or DRV/r over 96 weeks. CLINICAL TRIALS REGISTRATION: NCT00811954 and NCT00851799.

Randomized Controlled Trial of an Internet Application to Reduce HIV Transmission Behavior Among HIV Infected Men Who have Sex with Men.

We conducted a prospective, randomized controlled trial of an internet-based safer-sex intervention to reduce HIV transmission risk behaviors. HIV-infected men who have sex with men (n = 179) were randomized to receive a monthly internet survey alone or a monthly survey plus tailored risk reduction messages over 12 months. The primary outcome was the cumulative sexually transmitted infection (STI) incidence over 12 months. Secondary outcomes included self-reported unprotected sex with an at risk partner and disclosure of HIV status to partners. In a modified intent to treat analysis, there was no difference in 12-month STI incidence between the intervention and control arms (30 vs. 25 %, respectively; p = 0.5). Unprotected sex decreased and disclosure increased over time in both study arms. These improvements suggest that addition of the risk-reduction messages provided little benefit beyond the self-monitoring of risky behavior via regular self-report risk behavior assessments (as was done in both study arms).

Genital Epstein Barr Virus is associated with higher prevalence and persistence of anal human papillomavirus in HIV-infected men on antiretroviral therapy.

BACKGROUND: Epstein Barr virus (EBV) and human papillomavirus (HPV) can co-exist in pharyngeal and cervical malignancies. However, the natural history and factors associated with persistent HPV infection among HIV-infected men who have sex with men (MSM) are unclear. METHODS: 131 HIV-infected MSM were followed for 48 weeks and screened for multiple co-infections, including seminal EBV DNA and high risk (HR)-HPV messenger RNA (mRNA) at several sites (semen, anal, pharynx). Primary analysis tested if seminal EBV shedding was associated with increased prevalence of HR-HPV at baseline using univariate tests and multivariable logistic regression. In participants with detectable anal HR-HPV at baseline, we tested if presence of seminal EBV shedding at baseline was also predictive of reduced HR-HPV clearance by log-rank test (over 48 weeks of follow-up). RESULTS: Baseline prevalence of HR-HPV was: anal 44% (N = 54/121); pharynx 3.8% (N = 5/131); semen 7.1% (N = 7/98). Seminal EBV shedding was present in 28% of participants and was associated with more than double the prevalence of detectable anal HR-HPV mRNA (71.4% for EBV shedders versus 33.3% for non-shedders, p < 0.01). In participants with detectable anal HR-HPV at baseline, we found increased persistence of HR-HPV over 48 weeks of follow-up (measured as time to first negative HR-HPV test in the EBV shedding group (p < 0.01). CONCLUSIONS: Seminal EBV shedding was associated with an increased risk of having detectable anal HR-HPV in a cohort of HIV-infected MSM on suppressive ART. Future studies should examine if co-infection with EBV and HR-HPV may act synergistically in pathogenesis of anal cancer in HIV-infected individuals.

Changes in Bone Mineral Density After Initiation of Antiretroviral Treatment With Tenofovir Disoproxil Fumarate/Emtricitabine Plus Atazanavir/Ritonavir, Darunavir/Ritonavir, or Raltegravir.

BACKGROUND: Specific antiretroviral therapy (ART) medications and the severity of human immunodeficiency virus (HIV) disease before treatment contribute to bone mineral density (BMD) loss after ART initiation. METHODS: We compared the percentage change in BMD over 96 weeks in 328 HIV-infected, treatment-naive individuals randomized equally to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). We also determined whether baseline levels of inflammation markers and immune activation were independently associated with BMD loss. RESULTS: At week 96, the mean percentage changes from baseline in spine and hip BMDs were similar in the protease inhibitor (PI) arms (spine: -4.0% in the ATV/r group vs -3.6% in the DRV/r [P = .42]; hip: -3.9% in the ATV/r group vs -3.4% in the DRV/r group [P = .36]) but were greater in the combined PI arms than in the RAL arm (spine: -3.8% vs -1.8% [P < .001]; hip: -3.7% vs -2.4% [P = .005]). In multivariable analyses, higher baseline concentrations of high-sensitivity C-reactive protein, interleukin 6, and soluble CD14 were associated with greater total hip BMD loss, whereas markers of CD4(+) T-cell senescence and exhaustion (CD4(+)CD28(-)CD57(+)PD1(+)) and CD4(+) T-cell activation (CD4(+)CD38(+)HLA-DR(+)) were associated with lumbar spine BMD loss. CONCLUSIONS: BMD losses 96 weeks after ART initiation were similar in magnitude among patients receiving PIs, ATV/r, or DRV/r but lowest among those receiving RAL. Inflammation and immune activation/senescence before ART initiation independently predicted subsequent BMD loss.

Extended-Release Niacin Versus Fenofibrate in HIV-Infected Participants With Low High-Density Lipoprotein Cholesterol: Effects on Endothelial Function, Lipoproteins, and Inflammation.

BACKGROUND: Low levels of high-density lipoprotein cholesterol (HDL-C) are common in individuals with human immunodeficiency virus (HIV) infection, persist during antiretroviral therapy (ART), and are associated with increased cardiovascular disease (CVD) risk. METHODS: Virologically controlled participants without CVD on stable ART with low HDL-C (men <40 mg/dL, women <50 mg/dL) and triglycerides >150 mg/dL were randomized to receive open-label extended-release niacin 1500 mg/day with aspirin 325 mg/day or fenofibrate 200 mg/day for 24 weeks. The primary endpoint was the week 24 within-arm change in brachial artery flow-mediated dilation (FMD) in participants with complete follow-up scans. RESULTS: Of 99 participants, 74 had complete data (35 niacin, 39 fenofibrate). Median age was 45 years, 77% were male, median CD4(+) count was 561 cells/µL, and brachial FMD was 4.2%. Median HDL-C was 32 mg/dL for men and 38 mg/dL for women, low-density lipoprotein cholesterol was 103 mg/dL, and triglycerides were 232 mg/dL. In men, HDL-C increased a median of 3 mg/dL with niacin and 6.5 mg/dL with fenofibrate (P < .001 for both). In women, HDL-C increased a median of 16 mg/dL with niacin and 8 mg/dL with fenofibrate (P = .08 for both). After 24 weeks, there was no significant change in FMD in either arm; the median (interquartile range) change was +0.6% (-1.6 to 2.3) with niacin (P = .28) and +0.5% (-1.0 to 3.0) with fenofibrate (P = .19). Neither treatment significantly affected C-reactive protein, interleukin 6, or D-dimer levels. CONCLUSIONS: Despite improvements in lipids, niacin or fenofibrate treatment for 24 weeks did not improve endothelial function or inflammatory markers in participants with well-controlled HIV infection and low HDL-C. CLINICAL TRIALS REGISTRATION: NCT01426438.

Changes in Inflammation and Immune Activation With Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy: ACTG 5260s.

BACKGROUND: It is unclear whether the integrase inhibitor raltegravir (RAL) reduces inflammation and immune activation compared with ritonavir-boosted protease inhibitors (PIs). METHODS: In a prospective, randomized, multicenter clinical trial that included 328 human immunodeficiency type 1 (HIV-1)-infected, treatment-naive participants were randomized to receive tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or RAL. A total of 234 participants (71%) with HIV-1 RNA levels <50 copies/mL by week 24 were included. Plasma biomarkers of inflammation and coagulation that were analysed included high-sensitivity C-reactive protein, interleukin-6 (IL-6), GlycA, D-dimer, soluble CD14 (sCD14), sCD163, and sIL-2r; blood cellular markers included %CD38+DR+ of T-cell subsets and %CD14+CD16+ and%CD14(dim)CD16+ monocyte subsets. Changes from baseline were examined at earlier (24 or 48 weeks) and later (96 weeks) time points, with 95% confidence intervals on fold-change. Pairwise treatment groups were compared using Wilcoxon rank sum tests, with P values adjusted for false discovery rate control. RESULTS: Changes in biomarkers varied by regimen during the 96 weeks of follow-up as follows: hsCRP declined with ATV/r and RAL, IL-6 declined only with RAL, and GLycA decreased in all groups. D-dimer declined with ATV/r and DRV/r and was unchanged with RAL. Markers of T-cell activation and sCD163 (but not sCD14 and CD14-+CD16+) declined in all groups. CONCLUSIONS: Despite some differences in specific markers of inflammation and immune activation between the antiretroviral therapy (ART) regimens, we found no consistent evidence that the reduction of inflammation and immune activation with ART initiation was different between RAL and PI-based regimens. CLINICAL TRIALS REGISTRATION: NCT00811954 and NCT00851799.