by
Sara Gianella;
Vincent Marconi;
Baiba Berzins;
Constance A. Benson;
Paul Sax;
Carl J. Fichtenbaum;
Timothy Wilkin;
Millie Vargas;
Qianqian Deng;
Michelli F. Oliveira;
Carlee Moser;
Babafemi O. Taiwo
Background: Engagement in care is central to reducing mortality for HIV-infected persons and achieving the White House National AIDS Strategy of 80% viral suppression in the US by 2020. Where an HIV-infected person lives impacts his or her ability to achieve viral suppression. Reliable transportation access for healthcare may be a key determinant of this place-suppression relationship. Methods: ZIP code tabulation areas (ZCTAs) were the units of analysis. We used geospatial and ecologic analyses to examine spatial distributions of neighborhood-level variables (eg, transportation accessibility) and associations with: (1) community linkage to care, and (2) community viral suppression. Among Atlanta ZCTAs with data for newly diagnosed HIV cases (2006-2010), we used Moran I to evaluate spatial clustering and linear regression models to evaluate associations between neighborhood variables and outcomes. Results: In 100 ZCTAs with 8413 newly diagnosed HIV-positive residents, a median of 60 HIV cases were diagnosed per ZCTA during the 5-year period. We found significant clustering of ZCTAs with low linkage to care and viral suppression (Moran I = 0.218, P< 0.05). In high-poverty ZCTAs, a 10% point increase in ZCTA-level household vehicle ownership was associated with a 4% point increase in linkage to care (P = 0.02, R2 = 0.16). In low-poverty ZCTAs, a 10% point increase in ZCTA-level household vehicle ownership was associated with a 30% point increase in ZCTA-level viral suppression (P = 0.01, R2 = 0.08). Conclusions: Correlations between transportation variables and community-level care linkage and viral suppression vary by area poverty level and provide opportunities for interventions beyond individual-level factors.
by
Jeffrey L Lennox;
Edwin DeJesus;
Daniel S. Berger;
Adriano Lazzarin;
Richard B. Pollard;
Jose Valdez Ramalho Madruga;
Jing Zhao;
Hong Wan;
Christopher L. Gilbert;
Hedy Teppler;
Anthony J. Rodgers;
Richard J.O. Barnard;
Michael D. Miller;
Mark J. DiNubile;
Bach-Yen Nguyen;
Randi Leavitt;
Peter Sklar
Background: We analyzed the 96-week results in the overall population and in prespecified subgroups from the ongoing STARTMRK study of treatment-naive HIV-infected patients. Methods: Eligible patients with HIV-1 RNA (vRNA) levels >5000 copies per milliliter and without baseline resistance to efavirenz, tenofovir, or emtricitabine were randomized in a double-blind noninferiority study to receive raltegravir or efavirenz, each combined with tenofovir/emtricitabine. Results: At week 96 counting noncompleters as failures, 81% versus 79% achieved vRNA levels <50 copies per milliliter in the raltegravir and efavirenz groups, respectively [δ (95% confidence interval) = 2% (24 to 9), noninferiority P < 0.001]. Mean change in baseline CD4 count was 240 and 225 cells per cubic millimeter in the raltegravir and efavirenz groups, respectively [δ (95% confidence interval) = 15 (-13 to 42)]. Treatment effects were consistent across prespecified baseline demographic and prognostic subgroups. Fewer drug-related clinical adverse events (47% versus 78%; P < 0.001) occurred in raltegravir than efavirenz recipients. Both regimens had modest effects on serum lipids and glucose levels and on body fat composition. Conclusions: When combined with tenofovir/emtricitabine in treatment-naive patients, raltegravir exhibited durable antiretroviral activity that was noninferior to the efficacy of efavirenz through 96 weeks of therapy. Subgroup analyses were generally consistent with the overall findings. Both regimens were well tolerated.
by
Raj Medapalli;
Chirag R. Parikh;
Kirsha Gordon;
Sheldon T. Brown;
Adeel A. Butt;
Cynthia L. Gibert;
David Rimland;
Maria C. Rodriguez-Barradas;
Chung-Chou Chang;
Amy C. Justice;
John Chijiang He;
Christina M. Wyatt
Introduction: Approximately, 15% of HIV-infected individuals have comorbid diabetes. Studies suggest that HIV and diabetes have an additive effect on chronic kidney disease (CKD) progression; however, this observation may be confounded by differences in traditional CKD risk factors. Methods: We studied a national cohort of HIV-infected and matched HIV-uninfected individuals who received care through the Veterans Healthcare Administration. Subjects were divided into 4 groups based on baseline HIV and diabetes status, and the rate of progression to an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m was compared using Cox-proportional hazards modeling to adjust for CKD risk factors. Results: About 31,072 veterans with baseline eGFR ≥45 mL/min/1.73m 2 (10,626 with HIV only, 5088 with diabetes only, and 1796 with both) were followed for a median of 5 years. Mean baseline eGFR was 94 mL/min/1.73m 2 , and 7% progressed to an eGFR < 45 mL/min/1.73m 2 . Compared with those without HIV or diabetes, the relative rate of progression was increased in individuals with diabetes only [adjusted hazard ratio (HR) 2.48; 95% confidence interval (CI): 2.19 to 2.80], HIV only [HR: 2.80, 95% CI: 2.50 to 3.15] , and both HIV and diabetes [HR: 4.47, 95% CI: 3.87 to 5.17]. DISCUSSION:: Compared with patients with only HIV or diabetes, patients with both diagnoses are at significantly increased risk of progressive CKD even after adjusting for traditional CKD risk factors. Future studies should evaluate the relative contribution of complex comorbidities and accompanying polypharmacy to the risk of CKD in HIV-infected individuals and prospectively investigate the use of cART, glycemic control, and adjunctive therapy to delay CKD progression.
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Michael J. Vinikoor;
Anna Cope;
Cynthia L. Gay;
Guido Ferrari;
Kara S. McGee;
Joann D. Kuruc;
Jeffrey L Lennox;
David M. Margolis;
Charles B. Hicks;
Joseph J. Eron
Initiation of antiretroviral therapy during acute HIV-1 infection may prevent persistent immune activation. We analyzed longitudinal CD38+HLA-DR+ CD8+ T-cell percentages in 31 acutely infected individuals who started early (median 43 days since infection) and successful antiretroviral therapy, and maintained viral suppression through 96 weeks. Pretherapy a median of 72.6% CD8+ T cells were CD38+HLA-DR+, and although this decreased to 15.6% by 96 weeks, it remained substantially higher than seronegative controls (median 8.9%, P = 0.008). Shorter time to suppression predicted lower activation at 96 weeks. These results support the hypothesis that very early events in HIV-1 pathogenesis may result in prolonged immune dysfunction.
by
Cecile Lahiri;
Katherine B. Dugan;
Xianhong Xie;
Laura Reimers;
Robert D. Burk;
Kathryn Anastos;
Stewart Massad;
Isam-Eldin Eltoum;
Xiaonan Xue;
Gypsyamber D'Souza;
Lisa Flowers;
Joel M. Palefsky;
Lisa Rahangdale;
Howard D. Strickler;
Ighoverha Ofotokun
Invasive cervical cancer (ICC) is the third most common female malignancy and fourth most common cause of cancer death in women globally. The risk of ICC is several-fold higher in HIV-positive women than in HIV-negative women, as are the prevalence, incidence, and persistence of oncogenic human papillomavirus (oncHPV), the infectious cause of most ICC. Although use of effective highly-active antiretroviral therapy (HAART) has been associated with reduced oncHPV prevalence and incidence and increased regression of cervical lesions, the overall incidence of ICC has not decreased in HIV-positive women during the HAART era. By increasing survival, HAART may increase lifetime oncHPV infections, allowing accumulation of somatic mutations and epigenetic changes necessary for oncogenesis. Currently, no anti-viral medications are clinically approved to treat cervical HPV infections.
In vitro studies have shown that lopinavir (LPV), an HIV-1 protease inhibitor (PI) used in some HAART regimens, may have activity against oncHPV through inhibition of viral oncogene E6. Most recently, an early phase clinical trial conducted in Nairobi, Kenya studied topical application of LPV to the cervix; preliminary results showed that 21 of 23 women initially diagnosed with high-grade disease returned to normal on subsequent Papanicolaou (Pap) smears and showed visible regression of cervical lesions.
We therefore assessed the hypothesis that oral LPV use may be associated with decreased prevalence and increased clearance of oncHPV compared to other antiretroviral (ARV) regimens.
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Engi F. Attia;
Kathleen A. McGinnis;
Laura C. Feemster;
Kathleen M. Akgün;
Adeel A. Butt;
Christopher J. Graber;
Michael J. Fine;
Matthew Bidwell Goetz;
Maria C. Rodriguez-Barradas;
Margaret A. Pisani;
Hilary A. Tindle;
Sheldon T. Brown;
Guy W. Soo Hoo;
David Rimland;
Cynthia L. Gibert;
Laurence Huang;
Matthew S. Freiberg;
Catherine L. Hough;
Kristina Crothers
Background: Pulmonary infections remain more common in HIV-infected (HIV+) compared to uninfected individuals. The increase in chronic lung diseases among aging HIV+ individuals may contribute to this persistent risk. We sought to determine whether chronic obstructive pulmonary disease (COPD) is an independent risk factor for different pulmonary infections requiring hospitalization among HIV+ patients.
Methods: We analyzed data from 41,993 HIV+ Veterans in the nationwide Veterans Aging Cohort Study Virtual Cohort (VACS-VC) from 1996–2009. Using ICD-9 codes, we identified baseline comorbid conditions, including COPD, and incident community-acquired pneumonia (CAP), pulmonary tuberculosis (TB) and Pneumocystis jirovecii pneumonia (PCP) requiring hospitalization within two years after baseline. We used multivariable Poisson regression to determine incidence rate ratios (IRR) associated with COPD for each type of pulmonary infection, adjusting for comorbidities, CD4+ cell count, HIV viral load, smoking status, substance use, vaccinations and calendar year at baseline.
Results: Unadjusted incidence rates of CAP, TB and PCP requiring hospitalization were significantly higher among persons with COPD compared to those without COPD (CAP: 53.9 vs. 19.4 per 1,000 person-years; TB: 8.7 vs. 2.8; PCP: 15.5 vs. 9.2; p ≤0.001). In multivariable Poisson regression models, COPD was independently associated with increased risk of CAP, TB and PCP (IRR 1.94, 95% CI 1.64–2.30; IRR 2.60, 95% CI 1.70–3.97; and IRR 1.48, 95% CI 1.10–2.01, respectively).
Conclusions: COPD is an independent risk factor for CAP, TB and PCP requiring hospitalization among HIV+ individuals. As the HIV+ population ages, the growing burden of COPD may confer substantial risk for pulmonary infections.
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.
Background: Although modern combination antiretroviral therapy (cART) regimens are better tolerated and less complex than earlier treatments, regimen modification or discontinuation remains a concern.
Methods: We studied HIV Outpatient Study (HOPS) participants who initiated first or second cART regimens during: 1996–1999, 2000–2003, 2004–2007 and 2008–2011. We analyzed regimen durability (time to regimen modification) and success (achieving undetectable plasma HIV RNA) for first and second cART regimens using Kaplan-Meier curves and log-rank tests, and examined factors associated with durability and success of first cART regimen using proportional hazards models.
Results: Durability of cART was progressively longer for cART regimens initiated in more recent periods: median first cART regimen durations were 1.0, 1.1, 2.1 and 4.6 years in 1996–1999, 2000–2003, 2004–2007 and 2008–2011, and median second cART durations were 0.9, 1.2, 2.8 and 3.9 years, respectively (both p<0.001). Comparing 1996–1999 and 2008–2011, the percentage of patients who achieved an undetectable HIV RNA within 6 months of first cART initiation increased from 65% to 81%, and from 63% to 80% on second cART (both p<0.001). Among patients initiating first cART during 2008–2011, black non-Hispanic/Latino race/ethnicity and ≥twice daily dosing were significantly associated with higher rates of regimen modification (p<0.05), and higher baseline HIV RNA levels were associated with failure to achieve an undetectable HIV RNA (p<0.001).
Conclusions: Among HIV-infected U.S. adults in routine HIV care, durability of first and second cART regimens and the likelihood of prompt virologic suppression increased during 1996–2011, coincident with the availability of more tolerable, less complex cART options.
OBJECTIVES: To examine the associations of homophobia, racism, and resiliency with differences in prevalent HIV infection in black and white men who have sex with men (MSM). METHODS: The Involve[ment]t study is a cohort of black and white MSM aged 18-39 years in Atlanta, GA, designed to evaluate individual, dyadic, and community level factors that might explain racial disparities in HIV prevalence. Participants were recruited irrespective of HIV serostatus from community-based venues and from Internet advertisements and were tested for HIV. We assessed respondents' demographics, whether they had engaged in unprotected anal intercourse (UAI) within the past 6 months, and attitudes about perceived homophobia, perceived racism, and personal resiliency. RESULTS: Compared with white MSM, black MSM were less likely to report UAI in the past 6 months [odds ratio (OR): 0.59, confidence interval (CI): 0.44 to 0.80], more likely to be HIV positive (OR: 5.05, CI: 3.52 to 7.25), and - among those HIV positive - more likely to report not being aware of their HIV infection (OR: 2.58, CI: 1.18 to 5.65). Greater perceived racism was associated with UAI in the black sample (partial odds ratio: 1.48, CI: 1.10 to 1.99). Overall, perceived homophobia, perceived racism, and resilience were not associated with prevalent HIV infection in our samples. Greater resilience was associated with less perceived homophobia in both black and white samples (Spearman r = -0.27, P < 0.001, for both). CONCLUSION: Future studies of social discrimination at the institutional and network level, than at the individual level, may explain differences in HIV infection in black and white MSM.