Background. The role of suppressive HSV therapy in women coinfected with HSV-2 and HIV-1 taking highly active antiretroviral therapy (HAART) is unclear. Methods. 60 women with HIV-1/HSV-2 coinfection on HAART with plasma HIV-1 viral load (PVL) ≤75 copies/mL were randomized to receive acyclovir (N = 30) or no acyclovir (N = 30). PVL, genital tract (GT) HIV-1, and GT HSV were measured every 4 weeks for one year. Results. Detection of GT HIV-1 was not significantly different in the two arms (OR 1.23, P = 0.67), although this pilot study was underpowered to detect this difference. When PVL was undetectable, the odds of detecting GT HIV were 0.4 times smaller in the acyclovir arm than in the control arm, though this was not statistically significant (P = 0.07). The odds of detecting GT HSV DNA in women receiving acyclovir were significantly lower than in women in the control group, OR 0.38, P < 0.05. Conclusions. Chronic suppressive therapy with acyclovir in HIV-1/HSV-2-positive women on HAART significantly reduces asymptomatic GT HSV shedding, though not GT HIV shedding or PVL. PVL was strongly associated with GT HIV shedding, reinforcing the importance of HAART in decreasing HIV sexual transmission.
Due to life-enhancing effects of antiretroviral therapy, HIV-positive persons have the potential for long life comparable to their uninfected peers. Older women (age 50+) living with HIV (OWLH) are often an under-recognized aging group. We conducted a systematic review to examine psychosocial factors that impact how OWLH live, cope, and age with HIV. Initial key word search yielded 1527 records, and 21 studies met our inclusion criteria of original quantitative or qualitative research published between 2013 and 2016 with results specific to OWLH. These focused on health care and self-management, sexual health and risk, stigma, loneliness, mental health (depression, substance use), and protective factors (coping, social support, well-being). Due to the scarcity of studies on each topic and inconclusive findings, no clear patterns of results emerged. As the number of OWLH continues to grow, more research, including longitudinal studies, is needed to fully characterize the psychosocial factors that impact aging with HIV.
by
Julie R. Gaither;
Joseph L. Goulet;
William C. Becker;
Stephen Crystal;
E. Jennifer Edelman;
Kirsha Gordon;
Robert D. Kerns;
David Rimland;
Melissa Skanderson;
Amy C. Justice;
David A. Fiellin
Objective: Patients with substance use disorders (SUDs) prescribed long-term opioid therapy (LtOT) are at risk for overdose and mortality. Prior research has shown that receipt of LtOT in accordance with clinical practice guidelines has the potential to mitigate these outcomes. Our objective was to determine whether the presence of a SUD modifies the association between guideline-concordant care and 1-year all-cause mortality among patients receiving LtOT for pain. Methods: Among HIV+ and HIV- patients initiating LtOT (≥90 days opioids) between 2000 and 2010 as part of the Veterans Aging Cohort Study, we used time-updated Cox regression and propensityscore matching to examine - stratified by SUD status - the association between 1-year all-cause mortality and 3 quality indicators derived from national opioid-prescribing guidelines. Specifically, we examined whether patients received psychotherapeutic cointerventions (≥2 outpatient mental health visits), benzodiazepine coprescriptions (≥7 days), and SUD treatment (≥1 inpatient day or outpatient visit). These indicators were among those found in a previous study to have a strong association with mortality. Results: Among 17,044 patients initiating LtOT, there were 1048 (6.1%) deaths during 1 year of follow-up. Receipt of psychotherapeutic cointerventions was associated with lower mortality in the overall sample and was more protective in patients with SUDs (adjusted hazard ratio [AHR] 0.43, 95% confidence interval [CI] 0.33-0.56 vs AHR 0.65, 95% CI 0.53-0.81; P for interaction =0.002). Benzodiazepine copresc ribing was associated with higher mortality in the overall sample (AHR 1.41, 95% CI 1.22-1.63), but we found no interaction by SUD status (P for interaction =0.11). Among patients with SUDs, receipt of SUD treatment was associated with lower mortality (AHR 0.43, 95% CI 0.33-0.57). Conclusions: For clinicians prescribing LtOT to patients with untreated SUDs, engaging patients with psychotherapeutic and SUD treatment services may reduce mortality. Clinicians should also avoid, when possible, prescribing opioids with benzodiazepines.
We evaluated the risk of human immunodeficiency virus (HIV) transmission among serodiscordant couples with low adherence to antiretroviral therapy (ART).Data of heterosexual couples/partners in 2010 were extracted from an Internet-based system. Participants were then followed over the course of a year with 6- and 12-month assessments. Prevalence and density of HIV seroconversion were calculated for spouses/partners who did not have a positive HIV test results at baseline. We calculated the transmission odds ratio (OR) value stratified by personal characteristics and behavioral correlates at 6- and 12-month follow-up, as well as seroconversion in spouses/partners over the year.A total of 5544 HIV/AIDS patients and their spouses/partners were recruited in this cohort. Incidence of HIV seroconversion among HIV-negative spouse/partner was 63.7/100 person years (PYs) (430/674.9) at the 6-month follow-up and 33.2/100PYs (567/1707.1PYs) at 12 months. The OR value of transmission from female to male was 2.1 times higher than from male to females at 6 months and 2.3 times higher at 12 months (P < .001). The 55- to 64-year age group was most likely to transmit HIV to their spouses/partners, 2.2 times greater than the participants who were 65 years and older. Married participants were 2.4 times higher at 6 months and 2.5 times higher at 12 months to transmit HIV than divorced/widowed participants. Lastly, transmission among illiterate participants was 6.7 times higher at 6 months and 2.3 times higher at 12 months than those with an educational attainment of community college or above.High HIV seroconversion was observed in this cohort. Spouses/partners who were male had the highest risk of HIV acquisition; those aged 55 to 64 years, having married status, and are HIV-positive with less education were more likely to transmit HIV.
by
Thomas A. O'Bryan;
Brian K. Agan;
Russell P. Tracy;
Matthew S. Freiberg;
Jason F. Okulicz;
Kaku So-Armah;
Anuradha Ganesan;
David Rimland;
Tahaniyat Lalani;
Robert G. Deiss;
Edmund C. Tramont
Background: D-dimer blood levels in persons with HIV infection are associated with risk of serious non-AIDS conditions and death. Black race has been correlated with higher D-dimer levels in several studies. We examined the effects of race and HIV on D-dimer over time and the impact of viral load suppression by longitudinally comparing changes in levels among healthy young adult male African Americans and whites before HIV seroconversion and before and after initiation of antiretroviral therapy (ART).
Methods: We analyzed D-dimer levels and clinical and laboratory data of 192 participants enrolled in the US Military HIV Natural History Study, a 30-year cohort of military personnel infected with HIV. D-dimer levels were measured on stored sera from each participant at 3 time points: (1) before HIV seroconversion (Pre-SC), (2) ≥6 months after HIV seroconversion but before ART initiation (Post-SC), and (3) ≥6 months after ART with documented viral suppression (Post-ART). Levels were compared at each time point using nonparametric and logistic regression analysis.
Results: Compared with whites (n = 106), African Americans (n = 86) had higher D-dimer levels post-SC (P = 0.007), but in the same individuals, pre-SC baseline and post-ART levels were similar (P = 0.40 and P = 0.99, respectively). There were no racial differences in CD4 cell counts, HIV RNA viral load, time from estimated seroconversion to ART initiation, and duration on ART.
Conclusions: Observed longitudinally, racial differences in D-dimer levels were seen only during HIV viremia. Higher levels of D-dimer commonly observed in African Americans are likely due to factors in addition to race.
The soluble membrane attack complex (sMAC) represents the terminal product of the complement cascade. We enrolled 47 HIV + adults (12 of whom underwent a second visit at least 24 weeks after starting therapy) as well as 11 HIV negative controls. At baseline, cerebrospinal fluid (CSF) sMAC was detectable in 27.7% of HIV + individuals. CSF sMAC correlated with CSF HIV RNA levels and was more likely to be detectable in HIV + individuals on cART compared to HIV negative controls. In HIV + participants, there were negative association trends between sMAC and neurocognitive performance but these did not reach statistical significance.
by
Jorge Salinas;
Christopher Rentsch;
Vincent Marconi;
Janet Tate;
Matthew Budoff;
Adeel A. Butt;
Matthew S. Freiberg;
Cynthia L. Gibert;
Matthew Bidwell Goetz;
David Leaf;
Maria C. Rodriguez-Barradas;
Amy C. Justice;
David Rimland
Background. After adjustment for cardiovascular risk factors and despite higher mortality, those with human immunodeficiency virus (HIV+) have a greater risk of acute myocardial infarction (AMI) than uninfected individuals. Methods. We included HIV+ individuals who started combination antiretroviral therapy (cART) in the Veterans Aging Cohort Study (VACS) from 1996 to 2012. We fit multivariable proportional hazards models for baseline, time-updated and cumulative measures of HIV-1 RNA, CD4 counts, and the VACS Index. We used the trapezoidal rule to build the following cumulative measures: viremia copy-years, CD4-years, and VACS Index score-years, captured 180 days after cART initiation until AMI, death, last clinic visit, or 30 September 2012. The primary outcomes were incident AMI (Medicaid, Medicare, and Veterans Affairs International Classification of Diseases-9 codes) and death. Results. A total of 8168 HIV+ individuals (53 861 person-years) were analyzed with 196 incident AMIs and 1710 deaths. Controlling for known cardiovascular risk factors, 6 of the 9 metrics predicted AMI and all metrics predicted mortality. Time-updated VACS Index had the lowest Akaike information criterion among all models for both outcomes. A time-updated VACS Index score of 55+ was associated with a hazard ratio (HR) of 3.31 (95% confidence interval [CI], 2.11-5.20) for AMI and a HR of 31.77 (95% CI, 26.17-38.57) for mortality. Conclusions. Time-updated VACS Index provided better AMI and mortality prediction than CD4 count and HIV-1 RNA, suggesting that current health determines risk more accurately than prior history and that risk assessment can be improved by biomarkers of organ injury.
by
Matthew Triplette;
Engi Attia;
Kathleen Akgun;
Monica Campo;
Maria Rodriguez-Barradas;
Sudhakar Pipavath;
Shahida Shahrir;
Cherry Wongtrakool;
Matthew Bidwell Goetz;
Joon Kim;
Guy W. Soo Hoo;
Sheldon T. Brown;
Kristina Crothers
Background: Emphysema is more prevalent in HIV-infected (HIV+) patients independent of smoking behavior. Nonetheless, health effects of emphysema in this population are poorly understood. We determined whether emphysema is associated with a greater burden of pulmonary symptoms and a lower 6-minute walk distance (6MWD) in HIV+ compared with HIV-uninfected (HIV-) subjects. Methods: We performed a cross-sectional analysis of 170 HIV+ and 153 HIV- subjects in the Examinations of HIV-Associated Lung Emphysema (EXHALE) cohort study. Subjects completed a self-assessment of respiratory symptoms, pulmonary function testing, and 6MWD testing as well as a chest computed tomography to determine emphysema severity. We used regression models to determine the association of emphysema with respiratory symptoms and 6MWD in HIV+ subjects and compared this to HIV- subjects. Results: Models stratified by HIV status demonstrated an association between > 10% radiographic emphysema and chronic cough and/or phlegm and 6MWD in HIV+ subjects. These associations persisted among the subset without airflow obstruction: those with emphysema had 4.2 (95% confidence interval: 1.3 to 14) times the odds of chronic cough and/or phlegm and walked 60 m (95% confidence interval: 26 to 93) less distance than those without emphysema. There was no association between > 10% emphysema and symptoms or 6MWD in HIV- subjects. Conclusions: In our cohort, > 10% radiographic emphysema was associated with chronic cough and/or phlegm and lower 6MWD in HIV+ but not HIV- subjects. These findings were robust even among HIV+ subjects with milder forms of emphysema and those without airflow obstruction, highlighting the clinical impact of emphysema in these patients.
by
Luuk Gras;
Margaret May;
Lars Peter Ryder;
Adam Trickey;
Marie Helleberg;
Niels Obel;
Rodolphe Thiebaut;
Jodie L. Guest;
John Gill;
Heidi Crane;
Viviane Dias Lima;
Antonella D'Arminio Monforte;
Timothy R. Sterling;
Jose Miro;
Santiago Moreno;
Christoph Stephan;
Colette Smith;
Janet Tate;
Leah Shepherd;
Mike Saag
Background:An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV-uninfected individuals more likely and whether restoration depends on gender, age, and other individual characteristics.Methods:We determined median and quartile reference values for CD4 and CD8 cell counts and their ratio using cross-sectional data from 2309 HIV-negative individuals. We used longitudinal measurements of 60,997 HIV-positive individuals from the Antiretroviral Therapy Cohort Collaboration in linear mixed-effects models.Results:When baseline CD4 cell counts were higher, higher long-term CD4 cell counts and CD4:CD8 ratios were reached. Highest long-term CD4 cell counts were observed in middle-aged individuals. During the first 2 years, median CD8 cell counts converged toward median reference values. However, changes were small thereafter and long-term CD8 cell count levels were higher than median reference values. Median 8-year CD8 cell counts were higher when ART was started with <250 CD4 cells/mm 3 . Median CD4:CD8 trajectories did not reach median reference values, even when ART was started at 500 cells/mm 3 .Discussion:Starting ART with a CD4 cell count of ≥500 cells/mm 3 makes reaching median reference CD4 cell counts more likely. However, median CD4:CD8 ratio trajectories remained below the median levels of HIV-negative individuals because of persisting high CD8 cell counts. To what extent these subnormal immunological responses affect specific clinical endpoints requires further investigation.