Abstract Background People living with HIV have greater risk of cardiovascular diseases (CVD) than people without HIV and tend to have different risk profiles, including higher serum triglycerides and lower LDL cholesterol levels. Nuclear magnetic resonance (NMR) provides a detailed phenotype of lipoproteins. Purpose To examine the associations between lipoprotein particle concentrations and size and progression of coronary artery plaque among people living with and without HIV, and whether these associations differ by HIV serostatus. Methods Men with no clinical CVD in the Multicenter AIDS Cohort Study (MACS) who underwent a coronary CT angiography at baseline (2010-13) and follow-up (2015-17) were included. NMR spectroscopy was completed on fasting serum samples at baseline. Logistic regression models for the change in total coronary plaque volume (in tertiles) were estimated with NMR-derived lipoproteins as predictors. Levels were log-transformed and standardized to make results comparable. Models were adjusted for demographics, statin use and HIV serostatus (model 1) with addition of CVD risk factors (model 2). Interactions by HIV serostatus were also tested. Results A total of 549 men (314 with HIV; 235 without HIV) were included. Mean age was 53 ±7 years; 58% were White, 30% Black, and 12% Hispanic. Coronary plaque was present in 70% and plaque volume progressed in 79% of the cohort. Among men with HIV, 81% had undetectable HIV RNA and 12% had a diagnosis of AIDS at baseline. Men with HIV had significantly higher levels of small LDL-P, and total, medium and large VLDL-P levels compared to men without HIV, and lower levels of total, small and large HDL-P (Table 1). Men with HIV had significantly greater progression of plaque volume (37 mm3) compared to men without HIV (31 mm3, p<0.05). Levels of total and small LDL-P concentrations were directly associated with plaque progression, whereas large HDL-P was inversely associated with plaque progression in the combined sample (Model 2). Associations between total and small LDL-P with plaque progression were stronger in men with HIV than in men without HIV in models 1 and 2 (interaction p<0.01). While associations in fully adjusted models for total VLDL-P and small VLDL-P were significant in men without HIV, there were no significant associations between these particle concentrations with coronary plaque progression among men without HIV (interaction p< 0.01) (Model 2, Table 2). Conclusion Associations between lipid particle concentrations and coronary plaque progression differed between men with and without HIV, with stronger associations seen in men without HIV for total and small LDL-P. Despite having higher VLDL and lower HDL particle concentrations at baseline, these particle concentrations were only associated with plaque progression in men without HIV. Further research is needed to elucidate HIV specific factors for plaque progression to tailor risk reduction strategies.

People with HIV (PWH) experience greater declines in both muscle function and muscle mass with aging. Whether changes in muscle quality and quantity with aging differ between men and women with HIV and the implications on muscle function are not established. In coordinated substudies of the Multicenter AIDS Cohort Study and Women’s Interagency HIV Study, participants completed physical function and falls assessments; total trunk/thigh density, inversely related to fatty infiltration, and area were quantified from computed tomography (CT) scans. Generalized linear models were used to explore variables affecting density/area, and associations between area/density and physical function and falls. CT scans were available on 387 men (198 PWH) and 184 women (118 PWH). HIV serostatus was associated with greater lateralis, paraspinal, and hamstring area, but lower psoas area and density. Older age and female sex were associated with smaller trunk muscle area and lower density. Both lower muscle area and muscle density were associated with several measures of impaired physical function. The odds of falling were lower with greater hamstring density, but not associated with other measurers of muscle area or density. In summary, older adults with HIV appear to have smaller and less dense (fattier) psoas, a key component in truncal stability and hip flexion that could have implications on physical function. The longitudinal associations of muscle area and density with physical function require careful investigation, with a particular focus on characteristics and interventions that can preserve muscle area, density, and function over time.

Background: COVID-19 pandemic effects on ambulatory care services for persons living with HIV in the United States, including on frequency of office visits and HIV viral load (VL) testing, have not been well described. Methods: We analyzed longitudinal data of active patients (any encounter after January 1, 2020) at 8 HIV Outpatient Study (HOPS) sites. Monthly rates of all-inclusive encounters (office, lab, pharmacy, hospital, telemedicine [TM], phone, other), office and TM (O&T) visits, and HIV VL tests were derived from generalized linear mixed models, using data available from January 2010 to June 2020. We then assessed temporal trends and the adjusted effects of sociodemographic and clinical factors on the rates of O&T visits during the COVID-19 pandemic, in multivariable Poisson regression of data from January to June 2020. Results: Of 1251 active patients, 71% were male, 57% aged ≥ 50 years, 36% non-Hispanic white, 42% non-Hispanic black, 19% Hispanic/Latino, and 49% publicly insured. Median CD4 count was 680 cells/mm3 and 93% had suppressed ( 0.20). The increase in TM visits (2%) did not offset the decline in office visits (26%). The HIV VL testing rate fell by 50% in the first 6 months of 2020 among patients who had VL test done in 2019 (Figure). Conclusion: In the HOPS, the rates of office visits and HIV VL tests dropped precipitously after March 2020. The long-term implications for clinical outcomes and HIV viral suppression may not be evident at this time in the COVID-19 pandemic but HIV care sites need strategies to ensure patients maintain engagement in care and HIV laboratory monitoring.

Objectives We hypothesized that the increased prevalence of noninfectious comorbidities (NICMs) observed among HIV-infected patients may result in increased direct costs of medical care compared to the general population. Our objective was to provide estimates of and describe factors contributing to direct costs for medical care among HIV-infected patients, focusing on NICM care expenditure. Methods A case-control study analyzing direct medical care costs in 2009. Antiretroviral therapy (ART)-experienced HIV-infected patients (cases) were compared to age, sex, and race-matched adults from the general population, included in the CINECA ARNO database (controls). NICMs evaluated included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure. Medical care cost information evaluated included pharmacy, outpatient, and inpatient hospital expenditures. Linear regression models were constructed to evaluate predictors of total care cost for the controls and cases. Results There were 2854 cases and 8562 controls. Mean age was 46 years and 37% were women. We analyzed data from 29,275 drug prescription records. Positive predictors of health care cost in the overall population: HIV infection (β = 2878; confidence interval (CI) = 2001–3755); polypathology (β = 8911; CI = 8356–9466); age (β = 62; CI = 45–79); and ART exposure (β = 18,773; CI = 17,873–19,672). Predictors of health care cost among cases: Center for Disease Control group C (β = 1548; CI = 330–2766); polypathology (β = 11,081; CI = 9447–12,716); age < 50 years (β = 1903; CI = 542–3264); protease inhibitor exposure (per month of use; β = 69; CI = 53–85); CD4 count < 200 cells/mm3 (β = 5438; CI = 3082–7795); and ART drug change (per change; β = 911; CI = 716–1106). Conclusion Total cost of medical care is higher in cases than controls. Lower medical costs associated with higher CD4 strata are offset by increases in the care costs needed for advancing age, particularly for NICMs.

Toll‐like receptors (TLRs) are transmembrane receptors that activate cells of the innate immune systems upon recognition of pathogen‐associated molecular patterns. The TLR4 is an essential component of the innate immune response to various microorganisms. We investigated the impact of TLR4 polymorphism on development of opportunistic diseases in HIV‐infected patients.

s presented at the 13th International Workshop on Adverse Drug Reactions and Co-morbidities in HIV Rome, Italy, 14–16 July 2011 abstracts title page.indd 1 21/7/11 12:17:12s title page.indd 1 21/7/11 12:17:12 13th International Workshop on Adverse Drug Reactions and Co-morbidities in HIV v ORGANIZING COMMITTEE Chairs for 2011 Kathleen Mulligan University of California at San Francisco, CA, USA Peter Reiss University of Amsterdam, Amsterdam, the Netherlands Giovanni Guaraldi University of Modena, Modena, Italy Andrew Carr St Vincent’s Hospital, Sydney, Australia Jacqueline Capeau Faculty of Medicine Saint Antoine, INSERM, Paris, France David Cooper University of New South Wales, Sydney, Australia Stefan Mauss Center for HIV and Hepatogastroenterology, Düsseldorf, Germany Morrie Schambelan University of California at San Francisco, CA, USA Ian Weller University College London Medical School, London, UK SCIENTIFIC COMMITTEE Georg Behrens Medical School of Hannover, Hannover, Germany Todd Brown Johns Hopkins University, Baltimore, MD, USA Judith Currier University of California, Los Angeles, CA, USA Gregory Dore University of New South Wales, Sydney, Australia Michael Dubé University of Southern California, Los Angeles, CA, USA Julian Falutz Immune Deficiency Treatment Center, Montreal General Hospital, Montreal, Canada Steve Grinspoon Massachusetts General Hospital, Boston, MA, USA Carl Grunfeld University of California Medical Center, San Francisco, CA, USA Donald Kotler Columbia University, New York, NY, USA Jules Levin The National AIDS Treatment Advocacy Project, New York, NY, USA Jens Lundgren University of Copenhagen, Hvidovre, Denmark Esteban Martínez IDIPAPS Hospital Clinic, University of Barcelona, Barcelona, Spain Veronica Miller The George Washington University, Washington, DC, USA Graeme Moyle Chelsea and Westminster Hospital, London, UK Robert Munk AIDS INFO NET, Arroyo Seco, NM, USA Bill Powderly University College, Dublin, Ireland Massimo Puoti University Hospital, Brescia, Italy Willy Rozenbaum Hôpital Tenon, Université Pierre et Marie Curie, Paris, France Pablo Tebas University of Pennsylvania, Philadelphia, PA, USA Sharon Walmsley University Health Network, Toronto, Canada Heiner Wedemeyer Hannover Medical School, Hannover, Germany Kevin Yarasheski Washington University, St Louis, MO, USA

Background The clinical implications of a failure to achieve high CD4 cell counts while receiving virally suppressive highly active antiretroviral therapy (HAART) are uncertain. Methods We analysed data from HIV‐infected men participating in the Multicenter AIDS Cohort Study (MACS) to elucidate associations between CD4 cell counts achieved during virally suppressive HAART and risks of AIDS or death. Inclusion criteria were: CD4 cell count <200 cells/μL before HAART initiation; ≥2 viral load (VL) determinations after HAART initiation; and sustained viral suppression, defined as all VL <50 HIV‐1 RNA copies/mL, but allowing a single VL of 50–1000 copies/mL. Results One hundred and twenty‐one men were included; median age was 42 years. After first VL <50 copies/mL, six participants had a new AIDS diagnosis and seven died. The median CD4 cell count change/year (cells/μL) after first VL <50 copies/mL was zero among patients who either developed AIDS or died vs . 39 among those who did not meet either endpoint ( P =0.119). After controlling for time from HAART initiation to first VL <50 copies/mL, age at first VL <50 copies/mL, history of AIDS and antiretroviral therapy (ART) experience before HAART, the hazard ratio for AIDS or death at CD4 cell count of ≤200 vs . >350 cells/μL was 10.7 ( P =0.013), and at CD4 cell count of 201–350 vs . >350 cells/μL was 8.54 ( P =0.014). Conclusion In this cohort, lower CD4 cell count at the time of viral suppression was associated with increased risk of AIDS or death.

He et al. recently reported the absence of erythrocyte Duffy antigen/receptor for chemokines (DARC) expression leads to increased risk of acquiring HIV but slower rates of disease progression (He et al., 2008He W. Neil S. Kulkarni H. Wright E. Agan B.K. Marconi V.C. Dolan M.J. Weiss R.A. Ahuja S.K. Cell Host Microbe. 2008; 4: 52-62Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar). We had also hypothesized DARC may have a role in HIV pathogenesis and progression by either influencing the number of binding sites available to the virus and its consequent distribution or by acting as reservoir for chemokines, altering the pattern of their release and thereby decreasing in magnitude but prolonging in duration the immune activation by which DARC may influence HIV outcomes. To investigate this, we identified the Duffy genotype in African-American men from the Multicenter AIDS Cohort Study (MACS) and compared the time to AIDS and death. Sexually active homosexual or bisexual men, without known AIDS, were recruited as previously described (Kaslow et al., 1987Kaslow R.A. Ostrow D.G. Detels R. Phair J.P. Polk B.F. Rinaldo Jr., C.R. Am. J. Epidemiol. 1987; 126: 310-318Crossref PubMed Scopus (1021) Google Scholar). From 5622 men enrolled before 2001, 295 HIV-infected African American participants were genotyped. The sequence for the DARC polymorphisms of interest as described by Tournamille et al. and the primers were based on that reference sequence (Tournamille et al., 1995Tournamille C. Colin Y. Cartron J.P. Le Van Kim C. Nat. Genet. 1995; 10: 224-228Crossref PubMed Scopus (566) Google Scholar). Primary outcomes for analysis were time from HIV-1 seroconversion to AIDS and time to death. If seroconversion occurred prior to recruitment in the study, date of study entry was used as seroconversion date, while, for those who seroconverted during follow-up period, the midpoint between the dates of last HIV-negative visit and first HIV-positive visit was used. Exposure was defined first on the basis of erythrocyte promoter: those with the null mutation in the erythrocyte promoter are referred to as mutation type, where those expressing Fy, regardless of open reading frame (ORF) allele, are wild-type (wt). Participants can therefore be grouped as those who are homozygous for the null mutation (mt/mt), those who are heterozygous for the null mutation (mt/wt), or those who are homozygous for the wild-type (wt/wt). This analysis will reflect receptor numbers on red blood cells, which is proportional to a gene dosage effect (Woolley et al., 2000Woolley I.J. Hotmire K.A. Sramkoski R.M. Zimmerman P.A. Kazura J.W. Transfusion. 2000; 40: 949-953Crossref PubMed Scopus (40) Google Scholar). Second, groups or virtual phenotypes are defined on the basis of DARC expression, combining their ORF allele (Fya or Fyb) with their erythrocyte promoter mutation. This analysis reflects the type of receptor on red blood cells. The primary exposures in the analysis are the promoter genotype, for which wt/wt is the reference group. Covariates controlled for in multivariate analysis included calendar periods (before 1990 [reference group], 1990—1994, 1995—1999, and post-2000), age at HIV-1 infection, and highly active antiretroviral therapy (HAART) treatment experience prior to events. Calendar period and HAART use were treated as time-dependent covariates. Cox proportional hazard regression analysis models with time-dependent covariates were used to calculate the relative hazard for predictors by using SAS 9.1 (SAS Institute). The assumptions of the proportional hazards model were deemed accurate based on the insignificant coefficient of the interaction term evaluating key predictors and time that was obtained. Kaplan-Meier curves were generated by S-plus 8.1 (Insightful Corporation). An identical analysis was performed using promoter and open reading frame haplotypes, which reflect DARC phenotypes (Fy− is the reference group) as the primary exposure. In addition, the binomial test of proportions was used to compare the frequency distribution for DARC phenotype between HIV antibody-positive men in this study to a previously tested group of African-American blood donors. Of the 295 African-American men included in this study, 249 were HIV positive at the time of recruitment to the study (seroprevalent), and the remaining 46 seroconverted during follow-up. For the seroprevalent, the average age at study entry was 32.5 years old and median CD4+ T cell counts 505 cells/mm3. For seroconverters, average age at seroconversion was 32.1 years and median CD4+ T cells was 588 cells/mm3 at the first HIV positive visit. One hundred and seventy-four of the participants (59.0%) were homozygous for the erythrocyte promoter null mutation, ninety-eight (33.2%) heterozygous, and twenty-three (7.8%) had wt expression. Predicted values were 169, 109, and 18 respectively (rounded to the nearest integer). This distribution conforms to the Hardy-Weinberg equation (p = 0.087 when tested for violation). Overall, 104 developed AIDS (26 diagnosed before 1990, 52 diagnosed 1990–1994, 23 diagnosed 1995–1999, and 3 diagnosed after 2000) and 141 died (19 died before 1990, 62 died 1990–1994, 50 died 1995–1999, and 10 died after 2000) as of March 31, 2007. Univariately, time to AIDS or time to death did not differ for the mt/mt and mt/wt groups compared with the wt/wt group. Although there was a suggestion that those with the mutation had a worse prognosis (Figure 1A), this difference was not statistically significant. The trend, however, was in the opposite direction to that which might have been predicted on the basis of work from He et al., 2008He W. Neil S. Kulkarni H. Wright E. Agan B.K. Marconi V.C. Dolan M.J. Weiss R.A. Ahuja S.K. Cell Host Microbe. 2008; 4: 52-62Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar. Similarly, the survival curves (Figure 1B) suggested that the FyaFyb group had a better prognosis than the Fy- group, and the Fya group had a worse prognosis than the Fy−, but these differences did not reach statistical significance. Although the effect of erythroid promoter mutations slightly increased after accounting for calendar time, age, and use of HAART, this was not statistically significant when evaluating time to either AIDS or death (Table 1). The relationships observed with the DARC virtual phenotype (ORF/promoter genotype combinations) did not change when examined in a multivariate model, or with analysis of the Fyb genotype based on the promoter type (wt/wt or wt/mt), i.e., whether the individual was heterozygous or homozygous in their expression of Fyb. In addition, the FyaFyb wtwt group (n = 11 men, in which 1 man developed AIDS) had a lower risk of developing AIDS when compared to the reference group Fy-: univariate hazard ratio (HR) = 0.19, 95% CI: 0.03-1.40 (p = 0.104); multivariate HR = 0.18, 95% CI: 0.02-1.26 (p = 0.084).Table 1Multivariate Analysis of Time to AIDS, Death, and AIDS-Related Death (Expressed as Hazard Ratios)Time to AIDSTime to DeathTime to AIDS-Related DeathErythroid Promoter Mutationswt/wt111mt/mt1.42 (95% CI 0.65–3.11) p = 0.381.59 (95% CI 0.80–3.17) p = 0.181.72 (95% CI 0.69–4.32) p = 0.25mt/wt1.42 (95% CI 0.63–3.22) p = 0.401.48 (95% CI 0.72–3.03) p = 0.291.67 (95% CI 0.64–4.32) p = 0.29ORF/Promoter Genotype CombinationsFy−111Fya1.34 (95% CI 0.18−9.75) p = 0.772.29 (95% CI 0.56−9.41) p = 0.251.53 (95% CI 0.21−11.22) p = 0.68FyaFyb0.75 (95% CI 0.42−1.34) p = 0.330.75 (95% CI 0.46−1.22) p = 0.250.79 (95% CI 0.43−1.45) p = 0.44Fyb1.06 (95% CI 0.67−1.67) p = 0.800.90 (95% CI 0.60−1.36) p = 0.630.93 (95% CI 0.56−1.56) p = 0.79Fyb_mtwt0.99 (95% CI 0.61−1.63) p = 0.970.96 (95% CI 0.63−1.47) p = 0.860.97 (95% CI 0.57−1.66) p = 0.91Fyb_wtwt1.50 (95% CI 0.60−3.74) p = 0.390.57 (95% CI 0.18−1.80) p = 0.340.76 (95% CI 0.24−2.46) p = 0.65 Open table in a new tab We further conducted an analysis by restricting events to 87 AIDS-related deaths only (61.7% of all deaths), which gave similar results (Table 1). When we treated the 47 (33%) deaths of unknown causes as nondeath outcomes but censored them in the analysis, the results remained unchanged (data not shown). To determine whether any virtual phenotype (a defined combination of promoter and ORF genotypes) was overrepresented in the cohort studied, we compared the frequency distribution of virtual phenotypes to the phenotypic frequency in African Americans cited in standard texts (AABB, 1999AABBAABB Technical Manual.13th edition. AABB, Bethesda, MD1999Google Scholar). The frequency distribution of virtual phenotypes for the HIV-1-infected men were significantly different from that of the non-HIV-infected cohort, suggesting a possible difference in HIV acquisition risk, but in the direction opposite to that which may have been anticipated by the findings of He et al., 2008He W. Neil S. Kulkarni H. Wright E. Agan B.K. Marconi V.C. Dolan M.J. Weiss R.A. Ahuja S.K. Cell Host Microbe. 2008; 4: 52-62Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar. Respectively, the values were for Fy negative expression (Fy a−b−) 59% (174 patients) versus 68% in the blood donor population (p < 0.001), for Fya expression (Fy a+b−) 1% (2 patients) versus 9% in the blood donor population (p < 0.001), Fyb expression (Fy a−b+) 24% (70 patients) versus 22% in the blood donor population (p = NS), and for expression of both antigens (Fy a+b+) 17% (49 patients) versus 1% (p < 0.001). The study has several limitations. The cohort size is small but well described. The power is limited at 0.3 when comparing the proportion of any observed mutation to the expected one. Some polymorphisms, such as Fyb weak (0% in some cohorts of African origin) (Olsson et al., 1998Olsson M.L. Smythe J.S. Hansson C. Poole J. Mallinson G. Jones J. Avent N.D. Daniels G. Br. J. Haematol. 1998; 103: 1184-1191Crossref PubMed Scopus (76) Google Scholar) have not been tested for. Linkage disequilibrium, due to some known or unknown gene with an influence on HIV progression on chromosome 1 (Pogo and Chaudhuri, 2000Pogo A.O. Chaudhuri A. Semin. Hematol. 2000; 37: 122-129Abstract Full Text PDF PubMed Google Scholar) has not been completely excluded but might be expected to be seen to be in the same direction in all studies of African Americans. Our results appear discordant to those of He et al., 2008He W. Neil S. Kulkarni H. Wright E. Agan B.K. Marconi V.C. Dolan M.J. Weiss R.A. Ahuja S.K. Cell Host Microbe. 2008; 4: 52-62Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar. There are several potential reasons for this. We compared the time from HIV infection to AIDS and to death on the basis of genotype, while they assessed survival over time on the basis of ethnic origin and genotype. Furthermore, the number of patients assessed is significantly greater in their study. While our study populations were from different U.S. states, there are unlikely to be any major genetic differences in the groups studied on this basis. On the other hand, our findings are supported to those recently reported at a conference in a South African population (Julg et al., 2009Julg B. Reddy S. Van Der Stock M. Kulkarni S. Qi Y. Walker B. Carrington M. Ndung'U T. 16th Conference on Retroviruses and Opportunistic Infections. CROI, Montreal, Canada2009Google Scholar), and reproduction of the findings in multiple cohorts is likely to be the best test of validity. Why the results are discordant is not clear. One issue may be the choice of ancestry markers in the study of He et al. Those chosen are associated with HIV biology; however, the distribution of the markers in HIV-positive and -negative African Americans was reported to be similar. DARC is upregulated in inflammatory states, including transplant rejection, other forms of crescentic glomerulonephritis, vasculitis, and arthritis (Bruhl et al., 2005Bruhl H. Vielhauer V. Weiss M. Mack M. Schlondorff D. Segerer S. Rheumatology (Oxford). 2005; 44: 309-313Crossref PubMed Scopus (34) Google Scholar, Patterson et al., 2002Patterson A.M. Siddall H. Chamberlain G. Gardner L. Middleton J. J. Pathol. 2002; 197: 108-116Crossref PubMed Scopus (54) Google Scholar). In all of these studies, DARC is associated with endothelial rather than red cell expression. Polymorphisms in the red cell promoter have not been shown to alter endothelial expression of this protein. Despite evidence that DARC on red cells is able to bind chemokines, thereby altering in vitro and in vivo chemokine levels, there is limited evidence that this phenomenon alters outcomes in disease. This study supports the hypothesis that altered erythrocyte expression of DARC has minimal impact on HIV disease progression. Data in this manuscript were collected by the MACS, with centers (Principal Investigators) at the Johns Hopkins University Bloomberg School of Public Health (Joseph B. Margolick, Lisa Jacobson); Howard Brown Health Center and Northwestern University Medical School (John Phair); University of California, Los Angeles (Roger Detels, Beth Jamieson); and University of Pittsburgh (Charles Rinaldo). The MACS is funded by the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the National Cancer Institute. UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041. The website is located at http://www.statepi.jhsph.edu/macs/macs.html. I.J.W. is funded by the Covance Fellowship of the Royal Australasian College of Physicians. Duffy Antigen Receptor for Chemokines Mediates trans-Infection of HIV-1 from Red Blood Cells to Target Cells and Affects HIV-AIDS SusceptibilityHe et al.Cell Host & MicrobeJuly 17, 2008In BriefDuffy antigen receptor for chemokines (DARC) expressed on red blood cells (RBCs) influences plasma levels of HIV-1-suppressive and proinflammatory chemokines such as CCL5/RANTES. DARC is also the RBC receptor for Plasmodium vivax. Africans with DARC −46C/C genotype, which confers a DARC-negative phenotype, are resistant to vivax malaria. Here, we show that HIV-1 attaches to RBCs via DARC, effecting trans-infection of target cells. In African Americans, DARC −46C/C is associated with 40% increase in the odds of acquiring HIV-1. Full-Text PDF Open Archive

ObjectiveThe aim of the study was to describe longitudinal changes in serum lipids among HIV-infected men receiving highly active antiretroviral therapy (HAART) with long-term follow-up.MethodsA total of 304 HIV-infected men who initiated HAART and who had serum lipid measurements prior to and for up to 7 years after HAART initiation were identified from the Multicenter AIDS Cohort Study (MACS). Mean levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were examined at biannual time-points.ResultsSignificant lipid changes were seen within 0.5 years of HAART initiation but increases in TC (+1.09 mmol/L), LDL-C (+0.57 mmol/L), HDL-C (+0.16 mmol/L) and non-HDL-C (+0.91 mmol/L) reached peak levels 2-3 years after HAART initiation. Declines in serum TC, LDL-C and non-HDL-C in subsequent years occurred concurrently with a substantial increase in use of lipid-lowering medications (from 1% usage pre-HAART to 43% 6-7 years after HAART initiation) but the proportion of men who either were treated with cholesterol-lowering medication or had elevated cholesterol levels (> 5.18 mmol/L) did not change during the 2-7-year interval after HAART. Mean HDL-C also decreased after 2-3 years and was low (< 1.04 mmol/L) in 55% of HIV-infected men 6-7 years after HAART initiation.ConclusionsAtherogenic serum lipids increased early after the initiation of HAART, peaked at 2-3 years and remained high or required treatment thereafter. Low HDL-C levels persisted in the majority of men. The long-term effects of lipid abnormalities on cardiovascular risk and the effectiveness and toxicity of prolonged use of lipid-lowering medications in combination with HAART are not known.

Objective: To evaluate patients with cytomegalovirus (CMV) retinitis treated with intravenous cidofovir for long-term outcomes.Design: Patients with CMV retinitis enrolled in a randomized, controlled clinical trial of intravenous cidofovir as treatment for retinitis were followed for long-term outcomes, including 21 patients initially enrolled in the deferral group who received cidofovir therapy after progression of retinitis.Setting: Thirteen tertiary care clinics specializing in AIDS care and ophthalmology.Participants: Fifty-eight patients with AIDS and small peripheral CMV retinitis lesions.Interventions: Cidofovir 5 mg/kg once weekly for 2 weeks followed by low-dose maintenance cidofovir therapy (3 mg/kg) in 35 patients or high-dose maintenance (5 mg/kg) in 23 patients.Main outcome measures: Time to progression of retinitis, drug toxicities.Results: Median time to progression of retinitis was 2.5 months. Median time to discontinuation of cidofovir because of intolerance was 6.6 months, and did not differ significantly between the two maintenance doses. Median time to discontinuation of cidofovir for intolerance other than probenecid reaction was 16.3 months for patients treated with low-dose maintenance and 5.0 months for patients treated with high-dose maintenance (P = 0.021). Proteinuria of 2+ or more occurred at a rate of 1.22/person year. In patients with sufficient follow-up to determine resolution of proteinuria, 89.9% of episodes resolved, and the median time to resolution was 20 days. Rates of probenecid intolerance and of cidofovir-associated uveitis were 0.35/person-year, and 0.20/person-year, respectively.