Spinal manipulative therapy, Graston technique® and placebo for non-specific thoracic spine pain: A randomised controlled trial

Background Few controlled trials have assessed the efficacy of spinal manipulative therapy (SMT) for thoracic spine pain. No high quality trials have been performed to test the efficacy and effectiveness of Graston Technique® (GT), an instrument-assisted soft tissue therapy. The objective of this trial was to determine the efficacy of SMT and GT compared to sham therapy for the treatment of non-specific thoracic spine pain. Methods People with non-specific thoracic pain were randomly allocated to one of three groups: SMT, GT, or a placebo (de-tuned ultrasound). Each participant received up to 10 supervised treatment sessions at Murdoch University chiropractic student clinic over a 4 week period. The participants and treatment providers were not blinded to the treatment allocation as it was clear which therapy they were receiving, however outcome assessors were blinded and we attempted to blind the participants allocated to the placebo group. Treatment outcomes were measured at baseline, 1 week, and at one, three, six and 12 months. Primary outcome measures included a modified Oswestry Disability Index, and the Visual Analogue Scale (VAS). Treatment effects were estimated with intention to treat analysis and linear mixed models. \ud Results One hundred and forty three participants were randomly allocated to the three groups (SMT = 36, GT = 63 and Placebo = 44). Baseline data for the three groups did not show any meaningful differences. Results of the intention to treat analyses revealed no time by group interactions, indicating no statistically significant between-group differences in pain or disability at 1 week, 1 month, 3 months, 6 months, or 12 months. There were significant main effects of time (p  < 0.01) indicating improvements in pain and disability from baseline among all participants regardless of intervention. No significant adverse events were reported. Conclusion This study indicates that there is no difference in outcome at any time point for pain or disability when comparing SMT, Graston Technique® or sham therapy for thoracic spine pain, however all groups improved with time. These results constitute the first from a fully powered randomised controlled trial comparing SMT, Graston technique® and a placebo

Direct-Acting Antiviral Hepatitis C Treatment Cascade and Barriers to Treatment Initiation among US Men and Women with and without HIV

Background: People with HIV are disproportionately coinfected with hepatitis C virus (HCV) and experience accelerated liver-related mortality. Direct-acting antivirals (DAAs) yield high sustained virologic response (SVR) rates, but uptake is suboptimal. This study characterizes the DAA-era HCV treatment cascade and barriers among US men and women with or at risk for HIV. Methods: We constructed HCV treatment cascades using the Women's Interagency HIV Study (women, 6 visits, 2015-2018, n=2447) and Multicenter AIDS Cohort Study (men, 1 visit, 2015-2018, n=2221). Cascades included treatment-eligible individuals (ie, HCV RNA-positive or reported DAAs). Surveys captured self-reported clinical (eg, CD4), patient (eg, missed visits), system (eg, appointment access), and financial/insurance barriers. Results: Of 323/92 (women/men) treatment eligible, most had HIV (77%/70%); 69%/63% were black. HIV-positive women were more likely to attain cascade outcomes than HIV-negative women (39% vs 23% initiated, 21% vs 12% SVR); similar discrepancies were noted for men. Black men and substance users were treated less often. Women initiating treatment (vs not) reported fewer patient barriers (14%/33%). Among men not treated, clinical barriers were prevalent (53%). Conclusions: HIV care may facilitate HCV treatment linkage and barrier navigation. HIV-negative individuals, black men, and substance users may need additional support. Clinical trials registration: NCT00000797 (Women's Interagency HIV Study); NCT00046280 (Multicenter AIDS Cohort Study)

Decreases in markers of monocyte/macrophage activation after hepatitis C eradication in HIV/hepatitis C virus coinfected women

Objective:Eradication of hepatitis C virus (HCV) in HIV disease decreases liver and non-liver-related morbidity and mortality. Elevated markers of monocyte/macrophage activation (soluble CD163 and sCD14) are associated with excess non-AIDS morbidity and mortality in HIV. We examined the effect of HCV eradication on these markers in relation to change in hepatic fibrosis.Design:A nested substudy within a longitudinal observational cohortMethods:We studied 126 HIV/HCV-coinfected women successfully treated for HCV, with undetectable HCV RNA at least 12 weeks after therapy completion. sCD163 and sCD14 were measured in serum collected before and after HCV eradication. Results were correlated with changes in markers of hepatic fibrosis.Results:Mean age of participants was 56.3 years, mean CD4+cell count was 615, and 72% had suppressed HIV RNA. After treatment, sCD163 and sCD14 levels significantly decreased from pre-treatment levels in unadjusted analyses. After adjusting for age, race, hepatic fibrosis status, baseline HCV RNA, CD4 count and HIV RNA status, cigarette smoking, and alcohol use, the decreases in sCD163 and sCD14 remained significant. Decrease in pre-treatment to post-treatment sCD163 were significantly positively correlated with changes in FIB-4 (r = 0.250, P = 0.005) and APRI (r = 0.262, P = 0.003); similarly decrease in sCD14 was significantly positively correlated with changes in FIB-4 (r = 0.333, P = 0.0001) and APRI (r = 0.457, P &lt; 0.0001).Conclusion:HCV eradication is associated with significant reductions in monocyte/macrophage activation markers that correlate with reductions in markers of hepatic fibrosis. These findings support broad access to and early initiation of HCV treatment in order to decrease immune activation and improve health in HIV-infected persons

Molecular profiling of breast and lung cancer in women with HIV reveals high tumor mutational burden

Objective: This study compared the mutation profile and tumor mutational burden (TMB) in women with HIV (WWH) diagnosed with lung adenocarcinoma (n = 8) or breast ductal neoplasm (n = 13) who were enrolled into the Women's Interagency HIV Study (WIHS). Design: Previous studies tended to focus on single institutions based on sample availability. This study is based on a representative, multicenter cohort that represents the racial and ethnic composition of women with HIV in the United States Methods: The study sequenced the complete human exome of n = 26 cancer samples from HIV-positive women, using Ion torrent next-generation sequencing. The study cohort was compared with a HIV-negative cohort obtained from the Genomic Data Commons Data Portal of the NCI. Results: There were no differences in known cancer mutations between breast cancer and lung cancer that developed in WWH and those that developed in HIV-negative (HIV-) women; however, WWH presented a significantly higher TMB in comparison to HIV- patients. Seventy-five percent of lung cancers and 61% of breast cancers were defined as TMB-high (more than 10 mutation/mb of DNA). Conclusion: This study affirms the recommendation that WWH be included in clinical trials of novel treatments for these cancers. Although these data are preliminary, the high TMB in WLHV suggests, paradoxically, that this immune challenged population may benefit greatly from immune checkpoint inhibitor therapies

Human Immunodeficiency Virus Is Associated with Elevated FibroScan-Aspartate Aminotransferase (FAST) Score

Background: Whether human immunodeficiency virus (HIV) infection is associated with the development of nonalcoholic steatohepatitis (NASH) remains unclear. The FibroScan-aspartate aminotransferase (FAST) score was developed to identify patients who have histologic NASH with high nonalcoholic fatty liver disease activity score (NAS ≥4) and significant liver fibrosis (≥F2), which has been associated with higher risk of end-stage liver disease. We examined whether HIV infection is associated with elevated FAST score in a large United States (US) cohort. Methods: Vibration-controlled transient elastography was performed in 1309 women without history of chronic viral hepatitis enrolled from 10 US sites: 928 women with HIV (WWH) and 381 women without HIV (WWOH). We used multivariable logistic regression to evaluate associations of HIV, demographic, lifestyle, and metabolic factors with an elevated (>0.35) FAST score. Results: Median age of WWH and WWOH was 51 years and 48 years, respectively. Most (90%) WWH were on antiretroviral therapy and 72% had undetectable HIV RNA. Prevalence of elevated FAST score was higher among WWH compared to WWOH (6.3% vs 1.8%, respectively; P =. 001). On multivariable analysis, HIV infection was associated with 3.7-fold higher odds of elevated FAST score (P =. 002), and greater waist circumference (per 10 cm) was associated with 1.7-fold higher odds (P <. 001). In analysis limited to WWH, undetectable HIV RNA and current protease inhibitor use were independently associated with lower odds of elevated FAST score. Conclusions: Our findings suggest that HIV is an independent risk factor for NASH with significant activity and fibrosis. Studies validating FAST score in persons with HIV are warranted

Trends in Bacterial Vaginosis Prevalence in a Cohort of U.S. Women with and at Risk for HIV

Background: Women with human immunodeficiency virus (HIV) often have bacterial vaginosis (BV). The goal of this analysis was to assess how BV prevalence changed over time and across U.S. regions in enrollment cohorts of the Women's Interagency HIV Study. Methods: In a multisite study, BV was diagnosed retrospectively when pH and two of three other Amsel criteria were met. Prevalence was determined across four recruitment waves: 1994-5, 2001-2, 2011-2, and 2013-5. Generalized estimating equation multivariable logistic regression models assessed changes in visit prevalence across waves after controlling for HIV disease severity and other risks. Results: Among 4,790 women (3,539 with HIV and 1,251 without HIV), BV was diagnosed at 7,870 (12%) of 64,444 visits. Baseline prevalence across enrollment waves was 15.0%-19.2%, but declined in all cohorts, with prevalence in the initial cohort falling to 3.9% in the 1994-5 cohort after up to 21 years of continuous observation. Prevalence varied within U.S. regions. HIV status was not associated with BV. Conclusion: BV prevalence decreased with time in study. Prevalence varied across sites, but was not uniformly increased or decreased in any U.S. region. Clinical Trials.gov identifier: NCT00000797

Incident Non-AIDS Comorbidity Burden among Women with or at Risk for Human Immunodeficiency Virus in the United States

Background: Human immunodeficiency virus (HIV) infection may accelerate development of aging-related non-AIDS comorbidities (NACMs). The incidence of NACMs is poorly characterized among women living with HIV (WLWH). Methods: WLWH and HIV-seronegative participants followed in the Women's Interagency HIV Study (WIHS) through 2009 (when >80% of WLWH used antiretroviral therapy) or onward were included, with outcomes measured through 31 March 2018. Sociodemographics, clinical covariates, and prevalent NACM were determined at enrollment. We used Poisson regression models to determine incident NACM burden (number of NACMs accrued through most recent WIHS visit out of 10 total NACMs assessed) by HIV serostatus and age. Results: There were 3129 participants (2239 WLWH, 890 HIV seronegative) with 36 589 person-years of follow-up. At enrollment, median age was 37 years, 65% were black, and 47% currently smoked. In fully adjusted analyses, WLWH had a higher incident NACM rate compared with HIV-seronegative women (incidence rate ratio, 1.36 [95% confidence interval (CI), 1.02-1.81]). Incident NACM burden was higher among WLWH vs HIV-seronegative women in most age strata (HIV × age interaction: P = .0438), and women <25 years old had the greatest incidence rate ratio by HIV serostatus at 1.48 (95% CI, 1.19-1.84) compared with those in older age groups. Incident NACM burden was associated with traditional comorbidity risk factors but not HIV-specific indices. Conclusions: Incident NACM burden was higher among WLWH than HIV-seronegative women. This difference was most dramatic among women aged <25 years, a group for whom routine comorbidity screening is not prioritized. Established non-HIV comorbidity risk factors were significantly associated with incident NACM burden. More data are needed to inform best practices for NACM screening, prevention, and management among WLWH, particularly young women

The Prevalence and Burden of Non-AIDS Comorbidities Among Women Living With or at Risk for Human Immunodeficiency Virus Infection in the United States

Background: The prevalence and burden of age-related non-AIDS comorbidities (NACMs) are poorly characterized among women living with HIV (WLWH). Methods: Virologically suppressed WLWH and HIV-seronegative participants followed in the Women's Interagency HIV Study (WIHS) through at least 2009 (when >80% of WLWH used antiretroviral therapy) were included, with outcomes measured through 31 March 2018. Covariates, NACM number, and prevalence were summarized at most recent WIHS visit. We used linear regression models to determine NACM burden by HIV serostatus and age. Results: Among 3232 women (2309 WLWH, 923 HIV-seronegative) with median observation of 15.3 years, median age and body mass index (BMI) were 50 years and 30 kg/m2, respectively; 65% were black; 70% ever used cigarettes. WLWH had a higher mean NACM number than HIV-seronegative women (3.6 vs 3.0, P < .0001) and higher prevalence of psychiatric illness, dyslipidemia, non-AIDS cancer, kidney, liver, and bone disease (all P < .01). Prevalent hypertension, diabetes, and cardiovascular and lung disease did not differ by HIV serostatus. Estimated NACM burden was higher among WLWH versus HIV-seronegative women in those aged 40-49 (P < .0001) and ≥60 years (P = .0009) (HIV × age interaction, P = .0978). In adjusted analyses, NACM burden was associated with HIV, age, race, income, BMI, alcohol abstinence, cigarette, and crack/cocaine use; in WLWH, additional HIV-specific indices were not associated, aside from recent abacavir use. Conclusions: Overall, NACM burden was high in the cohort, but higher in WLWH and in certain age groups. Non-HIV traditional risk factors were significantly associated with NACM burden in WLWH and should be prioritized in clinical guidelines for screening and intervention to mitigate comorbidity burden in this high-risk population

Brief Report: PrEP Eligibility among At-Risk Women in the Southern United States: Associated Factors, Awareness, and Acceptability

Background:Among women in the United States, non-Latina black women in the South have disproportionately high rates of new HIV infections but low use of pre-exposure prophylaxis (PrEP). Effective strategies to identify factors associated with PrEP eligibility could facilitate improved screening, offering, and uptake of PrEP among US women at risk of HIV.Setting and methods:We applied 2014 CDC criteria for PrEP use to at-risk HIV-negative women enrolled in the Southern US sites (Atlanta, Chapel Hill, Birmingham/Jackson, Miami) of the Women's Interagency HIV Study from 2014 to 2015 to estimate PrEP eligibility and assess PrEP knowledge and acceptability. Factors associated with PrEP eligibility were assessed using multivariable models.Results:Among 225 women, 72 (32%) were PrEP-eligible; the most common PrEP indicator was condomless sex. The majority of PrEP-eligible women (88%) reported willingness to consider PrEP. Only 24 (11%) PrEP-eligible women had previously heard of PrEP, and only 1 reported previous use. Education level less than high school [adjusted odds ratio (aOR) 2.56; 95% confidence interval (CI): 1.22 to 5.37], history of sexual violence (aOR 4.52; 95% CI: 1.52 to 17.76), and medium to high self-perception of HIV risk (aOR 6.76; 95% CI: 3.26 to 14.05) were significantly associated with PrEP eligibility in adjusted models.Conclusions:Extremely low PrEP awareness and use despite a high proportion of eligibility and acceptability signify a critical need to enhance PrEP education and delivery for women in this region. Supplementing CDC eligibility criteria with questions about history of sexual violence and HIV risk self-assessment may enhance PrEP screening and uptake among US women

The Effect of Menopausal Status, Age, and Human Immunodeficiency Virus (HIV) on Non-AIDS Comorbidity Burden Among US Women

Menopause may impact the earlier onset of aging-related comorbidities among women with versus without human immunodeficiency virus (HIV). We found that menopausal status, age, and HIV were independently associated with higher comorbidity burden, and that HIV impacted burden most in the pre-/perimenopausal phases