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.

Simplification from twice-daily to once-daily darunavir/ritonavir in a randomized trial among HIV-infected persons with HIV-1 RNA suppression on antiretroviral therapy.

BACKGROUND: DRIVESHAFT is a randomized, open-label, 48-week clinical trial that examined virological outcomes and safety of antiretroviral simplification among virologically suppressed, treatment-experienced HIV-infected patients switching from darunavir/ritonavir (DRV/r) twice-daily-based regimens to a once-daily DRV/r component. METHODS: HIV-infected adults with a stable antiretroviral regimen including DRV/r 600/100 mg twice daily plus a minimum of two other antiretrovirals, <2 historical DRV-associated mutations and HIV RNA<40 copies/ml for at least 12 weeks prior to entry were eligible. Participants were randomized 1:1 to switch DRV/r to 800/100 mg once daily or maintain their current regimen. The primary end point was HIV-1 RNA<40 copies/ml at week 48 using the Snapshot algorithm. RESULTS: Demographics and baseline characteristics were similar between arms. Virological suppression was greater in the DRV/r once-daily (n=30) versus twice-daily (n=30) arm at week 48 (90.0% versus 83.3%; 95% CI: -11.5, 24.8). Three subjects discontinued the once-daily arm, with four discontinuations and one virological failure in the twice-daily arm. No discontinuations were related to adverse events. Reduction in LDL was significantly greater in the once-daily arm at week 24 (-8.0 mg/dl versus 3.3 mg/dl; P=0.04). There was a trend towards suboptimal adherence <90% to antiretrovirals among subjects taking twice-daily versus once-daily DRV/r by week 48 (12.0% versus 0.0%; P=0.06). CONCLUSIONS: Switching from twice-daily to once-daily DRV/r in virologically suppressed patients maintains virological control, with greater reduction in LDL cholesterol by 24 weeks. This study provides pilot data that could be used to design a non-inferiority study to definitively answer the question of whether switching from twice-daily to once-daily DRV/r maintains viral suppression. ClinicalTrials.gov number: NCT01423812.

Using sociometric measures to assess nonresponse bias.

PURPOSE: Much attention has been given to the potential nonresponse bias that occurs in epidemiologic studies that attempt to enroll a representative sample. Most analyses surrounding nonrespondents focus on individual-level attributes and how they vary across respondents and nonrespondents. Although these attributes are of interest, analysis of the social network position of nonrespondents as defined by traditional sociometric measures (i.e., centrality and bridging) has not been conducted, and could provide further insights into the validity of the sample. METHODS: We used data from the Secunderabadi Men's Study, a whole network of Indian men who have sex with men (MSM) generated using cell phone contact lists of men approached using Time Location Cluster Sampling. Multivariable logistic regression was used to determine whether demographic and behavioral attributes and indegree (the frequency of men who have sex with men was listed across all cell phone contact lists) were associated with being a respondent. RESULTS: A total of 239 respondents were interviewed and 81 were approached but did not consent to the interview ("nonrespondents"). CONCLUSIONS: Respondents were more likely to have higher indegree than nonrespondents, adjusting for attribute differences (odds ratio, 1.19; 95% confidence interval, 1.07, 1.34). This analysis suggests that the network position of nonrespondents may be important when considering the potential impact of nonresponse bias.

Socially-integrated transdisciplinary HIV prevention.

Current ideas about HIV prevention include a mixture of primarily biomedical interventions, socio-mechanical interventions such as sterile syringe and condom distribution, and behavioral interventions. This article presents a framework for socially-integrated transdisciplinary HIV prevention that may improve current prevention efforts. It first describes one socially-integrated transdisciplinary intervention project, the Transmission Reduction Intervention Project. We focus on how social aspects of the intervention integrate its component parts across disciplines and processes at different levels of analysis. We then present socially-integrated perspectives about how to improve combination antiretroviral treatment (cART) processes at the population level in order to solve the problems of the treatment cascade and make "treatment as prevention" more effective. Finally, we discuss some remaining problems and issues in such a social transdisciplinary intervention in the hope that other researchers and public health agents will develop additional socially-integrated interventions for HIV and other diseases.

Renal Function Recovery and HIV Viral Suppression Following Tenofovir Discontinuation for Renal Impairment.

BACKGROUND: Tenofovir associated nephrotoxicity (TDFN) is well recognized. This study describes the trend of renal function recovery and virologic consequences after cessation of tenofovir (TDF) for suspected TDFN. METHODS: This was a retrospective chart review of 241 patients who underwent HLA-B*5701 allele testing between January 2007-December 2010. Demographics and clinical characteristics were compared at baseline, 3, 6, and 12 month between patients that continued and discontinued TDF. Factors associated with renal function recovery were assessed by multivariable logistic regression. RESULTS: Eighty patients were identified with TDFN; 84% male, 74% African American (AA) with a median age of 55 years, and median length of TDF use for 122 weeks. Renal recovery at 12 months differed in those who stopped versus (vs.) continued TDF (83% vs. 57% p=0.03). In a crude analysis, baseline chronic kidney disease was negatively associated with renal recovery (p=0.01). An adjusted analysis showed that those who stopped TDF had 3.76 higher odds of renal recovery compared to those who did not stop TDF (95% CI: 1.26-11.27, p=0.02). There were no significant differences in virologic response after switching TDF to an alternative agent. CONCLUSION: In this mostly AA male population with suspected TDFN, discontinuation of TDF was strongly associated with renal function recovery without affecting viral suppression.

Estimating the number of young Black men who have sex with men (YBMSM) on the south side of Chicago: towards HIV elimination within US urban communities.

The rate of HIV infection among young Black men who have sex with men (YBMSM) aged 16-29 is increasing significantly in the United States. Prevention in this population would considerably impact future health-care resources given the need for lifelong antiretrovirals. A YBMSM population estimate is needed to assist HIV prevention program planning. This analysis estimates the number of YBMSM aged 16-29 living on the south side of Chicago (SSC), the Chicago HIV epicenter, as the first step in eliminating HIV in this population. Three methods were utilized to estimate the number of YBMSM in the SSC. First, an indirect approach following the formula a = k/b; where a = the estimated number of YBMSM, k = the average YBMSM HIV prevalence estimate, and b = the YBMSM population-based HIV seropositivity rate. Second, data from the most recent National Survey of Family Growth (NSFG) was used to estimate the proportion of Black men who report having sex with a man. Third, a modified Delphi approach was used, which averaged community expert estimates. The indirect approach yielded an average estimate of 11.7 % YBMSM, the NSFG yielded a 4.2 % (95 % CI 2.28-6.21) estimate, and the modified Delphi approach yielded estimates of 3.0 % (2.3-3.6), 16.8 % (14.5-19.1), and 25 % (22.0-27.0); an average of 14.9 %. The crude average of the three methods was 10.2 %. Applied to SSC, this results to 5,578 YBMSM. The estimate of 5,578 YBMSM represents a group that can be feasibly reached with HIV prevention efforts. Population estimates of those most at risk for HIV will help public health officials allocate resources, offering potential for elimination of new HIV cases.

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.

Vitamin D insufficiency may impair CD4 recovery among Women's Interagency HIV Study participants with advanced disease on HAART.

BACKGROUND: Recent studies in HIV-infected men report an association between low vitamin D (25OH-D) and CD4 recovery on HAART. We sought to test this relationship in the Women's Interagency HIV Study (WIHS). METHODS: We examined 204 HIV-infected women with advanced disease, who started HAART after enrollment in the WIHS. We measured vitamin D (25OH-D) levels about 6 months prior to HAART initiation. The relationship between CD4 recovery (defined as increases of ≥50, 100, and 200 cells at 6, 12, and 24 months) and exposure variables was examined using logistic regression models at 6, 12 and 24 months post-HAART initiation in unadjusted and adjusted analyses, and using multivariable longitudinal Generalized Estimating Equations (GEE). Vitamin D insufficiency was defined as 25OH-D levels at least 30 ng/ml. RESULTS: The majority were non-Hispanic black (60%) and had insufficient vitamin D levels (89%). In adjusted analyses, at 24 months after HAART, insufficient vitamin D level (OR 0.20, 95% CI 0.05-0.83) was associated with decreased odds of CD4 recovery. The undetectable viral load (OR 11.38, 95% CI 4.31-30.05) was associated with CD4 recovery. The multivariable GEE model found that average immune reconstitution attenuated significantly (P < 0.01) over time among those with insufficient vitamin D levels compared with those with sufficient vitamin D levels. CONCLUSION: Vitamin D insufficiency is associated with diminished late CD4 recovery after HAART initiation among US women living with advanced HIV. The mechanism of this association on late CD4 recovery may be late vitamin D-associated production of naive CD4 cells during immune reconstitution.

Anal intercourse and HIV risk among low-income heterosexual women: findings from Chicago HIV behavioral surveillance.

BACKGROUND: Anal intercourse (AI) is a highly efficient route for HIV transmission and has not been well elucidated among heterosexual (HET) women. Heterosexual women living in impoverished urban areas in the US are at increased risk for HIV acquisition. We aim to describe rates of AI and characteristics associated with AI among heterosexual women at increased risk for HIV acquisition living in Chicago. METHODS: The Chicago Department of Public Health conducted a survey of HET during 2007 as part of the National HIV Behavioral Surveillance System. Venue-based, time-location sampling was used to select participants from venues in high-risk areas (census tracts with concurrently high rates of heterosexual AIDS and household poverty). Eligible participants were interviewed anonymously and offered a HIV test. RESULTS: In total, 407 heterosexual women were interviewed. Seventy-one (17%) women reported having AI in the past 12 months, with 61 of the 71 (86%) reporting unprotected AI. In multivariate analysis, women who engaged in AI were more than three times as likely to have three or more sex partners in the past 12 months (OR=3.27, 95% CI 1.53-6.99). AI was also independently associated with STI diagnosis in the past 12 months (2.13, 95% CI 1.06-4.26), and having sexual intercourse for the first time before the age of 15 years (2.23, 95% CI 1.28-3.89). CONCLUSION: AI was associated with multiple high risk behaviors including a greater number of sexual partners, STI diagnosis, and earlier age at first sex. The combination of risk factors found to be associated with AI call for new HIV prevention services tailored to the needs of women and young girls living in poverty.