Human Immunodeficiency Virus Load Research Articles

Association Between Short Leukocyte Telomere Length and HIV Infection in a Cohort Study: No Evidence of a Relationship With Antiretroviral Therapy

Individuals infected with human immunodeficiency virus (HIV) appear to age faster than the general population, possibly related to HIV infection, antiretroviral therapy, and/or social/environmental factors. We evaluated leukocyte telomere length (LTL), a marker of cellular aging, in HIV-infected and uninfected adults. Clinical data and blood were collected from Children and women: AntiRetrovirals and the Mechanism of Aging (CARMA) cohort study participants. Variables found to be important in univariate analysis were multivariate model candidates. Of the 229 HIV-infected and 166 HIV-uninfected participants, 76% were women, and 71% were current/previous smokers. In a multivariate model of all participants, older age (P < .001), HIV infection (P = .04), active hepatitis C virus (HCV) infection (P = .02), and smoking (P < .003) were associated with shorter LTL. An interaction was detected, whereby smoking was associated with shorter LTL in HIV-uninfected subjects only. Among those, age and smoking (P ≤ .01) were related to shorter LTL. In 2 models of HIV-infected individuals, age (P ≤ .002) and either active HCV infection (P = .05) or peak HIV RNA ≥100 000 copies/mL (P = .04) were associated with shorter LTL, whereas other HIV disease or treatment parameters were unrelated. Our results suggest that acquisition of HIV and viral load are primarily responsible for the association between HIV-positive status and shorter LTL. The lack of association between LTL and time since HIV diagnosis, antiretroviral treatment, or degree of immune suppression would implicate HIV infection-related factors rather than disease progression or treatment. Smoking effects on LTL appear masked by HIV, and HCV infection may accelerate LTL shortening, particularly in coinfected individuals. The effect of early therapeutic intervention on LTL in HIV and HCV infections should be evaluated.

Factors Associated with Symptomatic Vulvovaginal Candidiasis: A Study among Women Attending a Primary Healthcare Clinic in Kwazulu-Natal, South Africa.

Background:Symptomatic vulvovaginal candidiasis (VVC) is one of the most common problems leading women to seek advice in primary healthcare facilities.Aim:The aim of this study is to describe the associations between some hypothesized factors and the presence of symptomatic VVC.Subjects and Methods:An analytical cross-sectional study was conducted. A total of 90 women diagnosed with symptomatic VVC and 108 women without symptomatic VVC were recruited when attending Umlazi D clinic, a primary health clinic in KwaZulu-Natal, South Africa between June 2011 and December 2011. Confirmed symptomatic VVC was determined by Gram stain and microbiological culture of vaginal swabs. For human immunodeficiency virus (HIV)-infected women, HIV ribonucleic acid load in plasma and genital fluid was determined by real-time-polymerase chain reaction (BioMerieux, Lyon, France). CD4 counts were obtained from patients’ medical records. Data were analyzed using the statistical package for the social sciences (SPSS) version 21.0 (SPSS Inc.; Chicago, IL, USA). Multiple logistic regression models were used to exclude univariate confounders. All tests were two-sided and a P < 0.05 was considered to be significant.Results:A total of 90% (81/90) of patients with symptomatic VVC complained of vulval itching, soreness and vaginal discharge when compared to 75.9% (82/108) of patients without symptomatic VVC (P < 0.01). Whilst pregnancy was independently associated with symptomatic VVC (P < 0.01), the latter was inversely related to Nugent's scores (P < 0.01). When compared with HIV negative women, the odds for symptomatic VVC increased among women with HIV-associated immunocompromise (CD4 counts < 200 cells/mm3, P < 0.001), significantly shedding HIV in their genital tracts (P = 0.04), with plasma HIV load > 1000 copies/mL (P < 0.001). There was a significant negative association between the use of highly active anti-retroviral therapy and the presence of symptomatic VVC in HIV-infected women (P < 0.01).Conclusion:Although symptomatic VVC is not classified as acquired immunodeficiency syndrome-related condition, HIV-related immune compromised women and particularly those who are anti-retroviral therapy-naïve are likely to develop symptomatic VVC.

Clinical and Biological Features Of Multiple Myeloma (MM) and Monoclonal Gammopathies In Patients With Human Immunodeficiency Virus (HIV) Infection

BackgroundMonoclonal gammopathies (MoG) and HIV infection are two common diseases. A higher incidence of MoG of undetermined significance (MGUS) has been suggested in HIV patients (pts).The clinical outcome of MGUS and the characteristics of MM in such patients are largely unknown. In the last decade, therapeutics advances have improved the prognosis of both diseases.We report the laboratory findings and clinical course of 18 HIV infected patients with a detectable serum monoclonal protein( MGUS, MM, plasma cell leukemia) treated in our center. Patients, disease and methodsPatients' demographic characteristics, stage of HIV infection and clinical course were studied. Laboratory studies included determination of CD 4 T-lymphocyte cell counts, HIV loads, serum protein electrophoresis, Ig isotype, hemoglobin, serum β2-microglobulin, calcium and creatinine levels, bone marrow aspiration with cytogenetic analysis at diagnosis. Results18 pts (9 MGUS/stage I asymptomatic myeloma, 6 stage III myeloma, 1 leukemia plasma cell and 2 multiple plasmocytomas) were studied. The median age at diagnosis was 54.5 years (38,75). The median age at diagnosis of HIV infection was 42 years (29,68). the time Median between seropositivity and monoclonal gammopathy was 10.5 years. 1 patient's HIV status was discovered during the treatment of myeloma. 14 patients received protease inhibitors, including 9 before developing gammopathy. The monoclonal gammapathy was IgG Kappa for 9 patients,IgG Lambda for 6.At the diagnosis of gammopathyt the median CD 4 T lymphocyte count was 442 cells/µL(range 190-915). Half of the patients had negative HIV viral load (the median of the others was 9904 copies/ml).A polyclonal hypergammaglobulinemia (median 15.4 g / l (3.6, 26.9)) was found in addition to the Ig monoclonal in 17 patients and one patient had a symptomatic immunoparesis with repeated infections. Two patients with asymptomatic MM progressed with a period of time of 6and 11 years.All patients with symptomatic myeloma had bone lesions, 3 had an hypercalcemia ( including a case of primary hyperparathyroidism), 2 patients had kidney injury ( 1 end stage renal disease requiring hemodialysis). Extramedullary lesions were found in 5 patients (lymph node).11 patients have been treated with chemotherapy, 4 received autologous stem cell transplantation and 7 relapsed. The median event free survival was 4 years. 4 patients died of disease. The overal survivalwas 4.25 years. ConclusionThe presence of a monoclonal gammapathy or asymptomatic myeloma with infection by the human immunodeficiency virus does not seem to change the clinical presentation at diagnosis. The prognosis myeloma does not seem different from the HIV non infected patients population infected and justifies a similar therapeutic approach, including therapeutic intensification and novel agents. Disclosures:No relevant conflicts of interest to declare.

Developments in CD4 and Viral Load Monitoring in Resource-Limited Settings

CD4 counts and human immunodeficiency virus (HIV) load testing are essential components of HIV care, and making these tests available in resource-limited settings is critical to the roll-out of HIV treatment globally. Until recently, the evidence supporting the importance of laboratory monitoring in resource-limited settings was lacking, but there is now a consensus emerging that testing should become routine to ensure the longevity of treatment programs. Low-cost, point-of-care testing offers the potential to fill this role as it potentially improves all aspects of HIV care, ranging from the diagnosis and staging of HIV infection in both infants and adults to monitoring for treatment failure once antiretroviral therapy has been initiated. It is imperative for low-cost solutions to become a reality, but it is equally imperative that close scrutiny be given to each new device that hits the market to ensure they perform optimally in all settings.

Recalcitrant Pseudotumoral Anogenital Herpes Simplex Virus Type 2 in HIV-Infected Patients: Evidence for Predominant B-Lymphoplasmocytic Infiltration and Immunomodulators as Effective Therapeutic Strategy

In patients with human immunodeficiency virus (HIV) infection, genital herpetic lesions may be extensive and tend to persist for longer periods; in addition, atypical hypertrophic, ulcerative, or pseudotumor forms have been reported, frequently showing resistance to acyclovir (ACV) treatment. Between 2003 and 2011, 10 HIV-1-infected patients presenting with chronic pseudotumoral anogenital herpes simplex type 2 (HSV-2) infections were studied. All patients developed chronic, hypertrophic HSV-2 anogenital lesions with multilesional presentation in 7 cases and involvement of 2 anatomical sites in 6 of them. At the time of diagnosis, the median CD3(+)CD4(+) absolute blood count was 480.5 cells/µL (range, 165-632 cells/µL), whereas the plasma HIV load was undetectable in all cases. Histopathologic analysis of lesion biopsies showed a moderately dense dermal polytypic plasma cell infiltrate. Detection of HSV-2 by culture and/or polymerase chain reaction was positive for all patients, with evidence for ACV-resistant strains in 6 of 8 cases. In addition, viral resistance to ACV was found only in HSV-2 isolated from ulcerative lesions, whereas purely pseudotumoral ones harbored sensitive strains. Durable control was observed with HSV DNA polymerase inhibitors in only 2 cases, and the immunomodulators imiquimod and thalidomide allowed 5 patients to reach sustained complete response. HSV-2-related pseudolymphoma in HIV-infected patients is characterized by a predominant polyclonal lymphoplasmacytic infiltration, and is frequently refractory to antiherpetic drugs. Immunomodulatory therapeutic strategies using thalidomide showed consistent efficacy, and should be considered early during the course of disease.

Inflammatory Mechanisms in HIV-Associated Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a severe complication of human immunodeficiency virus (HIV) infection and a leading major cause of death when present. HIV-PAH could be the consequence of multiple hits including the direct effects of HIV proteins, use of illicit drugs, and chronic inflammation. Indeed, HIV infection has long been identified as an immunosuppressive disease but, since the advent of highly active antiretroviral treatments (HAART), HIV infection is considered as an inflammatory disease in which vascular complications have become a major cause of morbidity and death. Conversely to immunosuppression, which correlates with blood CD4 + T cell level, inflammation in HIV infection is due to the lack of gut CD4 + T cell restoration. Such gut T cell depletion favors lipopolysaccharide translocation and, in turn, chronic systemic interleukin-6 overproduction. Conversely to blood CD4 + T cells, gut CD4 + T cells are only partially restored with HAART, usually slowly after several months or years, with a large heterogeneity from one patient to another. These characteristics may cause chronic inflammation, and we hypothesize that PAH may occur because of this inflammatory component despite HAART, even with apparently good response to therapy (i.e., blood CD4 + T cell normalization and undetectable HIV load). Inflammation theory in HIV-PAH (as in other forms of PAH) could open new treatment options.

Neoplasms and infections as the main causes of death in patients in complete response to HIV‐related non‐Hodgkin lymphoma in the combination antiretroviral therapy era: a study out of a series of 146 patients

Neoplasms and infections as the main causes of death in patients in complete response to HIV‐related non‐Hodgkin lymphoma in the combination antiretroviral therapy era: a study out of a series of 146 patients

CD133+ Hematopoietic Progenitor Cells Harbor HIV Genomes in a Subset of Optimally Treated People With Long-Term Viral Suppression

Hematopoietic progenitor cells (HPCs) in the bone marrow of human immunodeficiency virus (HIV)-infected individuals have been proposed as a persistent reservoir of virus. However, some studies have suggested that HIV genomes detected in HPCs arise from T-cell contamination. CD133-sorted HPCs and CD133-depleted bone marrow cells were purified from bone marrow specimens obtained from 11 antiretroviral-treated donors in whom the HIV load had been <48 copies/mL for at least 6 months. CD133 and CD3 expression on the cells was assessed by flow cytometry. HIV DNA was quantified by real-time polymerase chain reaction analysis. HIV genomes were detected in CD133-sorted samples from 6 donors, including 2 in whom viral loads were undetectable for >8 years. CD3(+) T cells represented <1% of cells in all CD133-sorted samples. For 5 of 6 CD133-sorted samples with detectable HIV DNA, the HIV genomes could not be explained by contaminating CD3(+) T cells. Donors with detectable HIV DNA in HPCs received their diagnosis significantly more recently than the remaining donors but had had undetectable viral loads for similar periods. HIV genomes can be detected in CD133-sorted cells from a subset of donors with long-term viral suppression and, in most cases, cannot be explained by contamination with CD3(+) T cells.

CD8 Encephalitis in HIV-Infected Patients Receiving cART: A Treatable Entity

Despite its overall efficacy, combined antiretroviral therapy (cART) has failed to control human immunodeficiency virus (HIV) infection of the central nervous system (CNS). New acute and chronic neurological complications continue to be reported. We conducted a retrospective study of 14 HIV-infected patients with documented encephalitis, which was initially attributed to an undetermined origin. Brain magnetic resonance imaging (MRI) uniformly revealed unusual, multiple linear gadolinium-enhanced perivascular lesions. All patients had manifested acute or subacute neurological symptoms; the brain MRIs indicating diffuse brain damage. The mean duration of HIV infection was approximately 10 years, and 8 patients were immunovirologically stable. Cerebrospinal fluid abnormalities with mildly elevated protein and pleocytosis with >90% lymphocytes, predominantly CD8, were found in all but 1 patient. The mean cerebral spinal fluid HIV load was 5949 copies/mL. Six patients reported a minor infection a few days prior to neurological symptoms, 2 patients presented criteria for the immune reconstitution inflammatory syndrome of the CNS, 2 were in virological escape, and 1 developed encephalitis after interruption of cART. Brain biopsies revealed inflammatory encephalitis associated with astrocytic and microglial activation as well as massive perivascular infiltration by polyclonal CD8(+) lymphocytes. All patients had been treated with glucocorticosteroids. The long-term therapeutic response varied from excellent, with no sequalae (n = 5), to moderate, with cognitive disorders (n = 4). The mean survival time was 8 years; however, 5 patients died within 13 months of initiation of treatment. CD8 encephalitis in HIV-infected patients receiving cART is a clinical entity that should be added to the list of HIV complications.

Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study

BackgroundChronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infected individuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwide cross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identify parameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBV viremia.MethodsA multicenter collaborative cross-sectional study was launched in 19 French University hospitals distributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiological characteristics of 223 HBV-HIV co-infected patients with an HBV replication over 1000 IU/mL were investigated.ResultsPatients were mostly male (82%, mean age 42 years). Genotype distribution (A 52%; E 23.3%; D 16.1%) was linked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic pattern highlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) under antiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypic lamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4 count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesions were observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viral load or genotype. Immune escape HBsAg variants were seldom detected.ConclusionsDespite the detection of advanced liver lesions in most patients, few were not receiving anti-HBV drugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimal adherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver disease progression. These findings are strong arguments to further optimize clinical management and to promote vaccination in HIV-infected patients.

Immunogenetics: Genome-Wide Association of Non-Progressive HIV and Viral Load Control: HLA Genes and Beyond.

Very early after the identification of the human immunodeficiency virus (HIV), host genetics factors were anticipated to play a role in viral control and disease progression. As early as the mid-1990s, candidate gene studies demonstrated a central role for the chemokine co-receptor/ligand (e.g., CCR5) and human leukocyte antigen (HLA) systems. In the last decade, the advent of genome-wide arrays opened a new era for unbiased genetic exploration of the genome and brought big expectations for the identification of new unexpected genes and pathways involved in HIV/AIDS. More than 15 genome-wide association studies targeting various HIV-linked phenotypes have been published since 2007. Surprisingly, only the two HIV-chemokine co-receptors and HLA loci have exhibited consistent and reproducible statistically significant genetic associations. In this chapter, we will review the findings from the genome-wide studies focusing especially on non-progressive and HIV control phenotypes, and discuss the current perspectives.

Direct passive hemagglutination test for rapid quantification of plasma load of the &amp;lt;i&amp;gt;Human Immunodeficiency Virus&amp;lt;/i&amp;gt;

An inexpensive and rapid test for determining titers of Human Immunodeficiency Virus (HIV) in plasmas was developed. Washed sheep red blood cells were applied onto HIV positive plasmas, in V-bottomed microtiter plates, to complement the HIV antigens and antibodies present in plasmas. The setup was incubated for 30 minutes at 37℃. Reciprocal of the highest dilution of each plasma which gave passive agglutination of the RBCs was read as its HIV titer. Mean HIV load of five samples, was ≥ 4096.00 ± 0.00 after one day of storage at 4℃ but it reduced to 256.00 ± 70.10, 28.80 ± 3.20, 7.20 ± 0.80 and 1.60 ± 0.98 on days 2, 3, 4 and 7, respectively. HIV antibodies were still detectable, by ELISA, in plasma dilutions that were tested negative with the new test. It was concluded that when HIV antibodies have been confirmed, or added to plasmas, passive hemagglutination test can be applied to assess their viral loads.

HIV Incidence Determination in the United States: A Multiassay Approach

Accurate testing algorithms are needed for estimating human immunodeficiency virus (HIV) incidence from cross-sectional surveys. We developed a multiassay algorithm (MAA) for HIV incidence that includes the BED capture enzyme immunoassay (BED-CEIA), an antibody avidity assay, HIV load, and CD4(+) T-cell count. We analyzed 1782 samples from 709 individuals in the United States who had a known duration of HIV infection (range, 0 to >8 years). Logistic regression with cubic splines was used to compare the performance of the MAA to the BED-CEIA and to determine the window period of the MAA. We compared the annual incidence estimated with the MAA to the annual incidence based on HIV seroconversion in a longitudinal cohort. The MAA had a window period of 141 days (95% confidence interval [CI], 94-150) and a very low false-recent misclassification rate (only 0.4% of 1474 samples from subjects infected for >1 year were misclassified as indicative of recent infection). In a cohort study, annual incidence based on HIV seroconversion was 1.04% (95% CI, .70%-1.55%). The incidence estimate obtained using the MAA was essentially identical: 0.97% (95% CI, .51%-1.71%). The MAA is as sensitive for detecting recent HIV infection as the BED-CEIA and has a very low rate of false-recent misclassification. It provides a powerful tool for cross-sectional HIV incidence determination.

Effect of Early Syphilis Infection on Plasma Viral Load and CD4 Cell Count in Human Immunodeficiency Virus–Infected Men

Concomitant syphilis and human immunodeficiency virus (HIV) infection is increasingly frequent in industrialized countries. From a large hospital cohort of HIV-infected patients followed up in the Paris area between 1998 and 2006, we examined the effect of early syphilis on plasma HIV-1 RNA levels and CD4 cell counts. We compared 282 HIV-1-infected men diagnosed as having incident primary or secondary syphilis with 1233 syphilis-free men matched for age (±5 years), sexual orientation, participating center, length of follow-up (±6 months), and immunologic and virologic status before the date of syphilis diagnosis (index date). Increase in viral load (VL) (plasma HIV-1 RNA) of at least 0.5 log or a rise to greater than 500 copies/mL in patients with previously controlled VL during the 6 months after the index date was analyzed, as were CD4 cell count variations and CD4 slope after the index date. During the 6 months after the index date, VL increase was observed in 77 men with syphilis (27.3%) and in 205 syphilis-free men (16.6%) (adjusted odds ratio [aOR], 1.87; 95% CI, 1.40-2.49). Even in men with a VL of less than 500 copies/mL undergoing antiretroviral therapy, syphilis was associated with a higher risk of VL increase (aOR, 1.52; 95% CI, 1.02-2.26). The CD4 cell count decreased significantly (mean, -28/μL) compared with the syphilis-free group during the syphilis episode (P = .001) but returned to previous levels thereafter. In HIV-infected men, syphilis was associated with a slight and transient decrease in the CD4 cell count and with an increase in VL, which implies that syphilis may increase the risk of HIV transmission, even in patients receiving antiretroviral therapy and with a VL of less than 500 copies/mL.

GB virus C viremia is associated with higher levels of double-negative T cells and lower T-cell activation in HIV-infected individuals receiving antiretroviral therapy.

Double-negative T cells (DNTCs; ie, CD3(+)CD4(-)CD8(-) T cells) play a role in limiting chronic immune activation. GB virus C (GBV-C) infection is associated with reduced T-cell activation in human immunodeficiency virus (HIV)-infected individuals. T-cell activation and DNTCs were measured in HIV-infected subjects with a nondetectable HIV load. GBV-C-viremic subjects had significantly reduced CD4(+) and CD8(+) T-cell activation (P=.003 and .034, respectively) and significantly increased DNTCs (P=.038), compared with nonviremic subjects. GBV-C load correlated with DNTC percentage (P=.004). Thus, GBV-C infection is associated with an increase in DNTCs, which may contribute to reduced immune activation during HIV infection.

-defensin Genomic Copy Number Is Associated With HIV Load and Immune Reconstitution in Sub-Saharan Africans

AIDS, caused by the retrovirus human immunodeficiency virus (HIV), is the leading cause of death of economically active people (age, 15-59 years) in sub-Saharan Africa. The host genetic variability of immune response to HIV and immune reconstitution following initiation of highly active antiretroviral therapy (HAART) is poorly understood. Here we focused on copy number variation of the β-defensin genes, which have been shown to have anti-HIV activity, and are important chemoattractants for Th17 lymphocytes via the chemokine receptor CCR6. We determined β-defensin gene copy number for 1002 Ethiopian and Tanzanian patients. We show that higher β-defensin copy number variation is associated with increased HIV load prior to HAART (P=.005) and poor immune reconstitution following initiation of HAART (P=.003). We suggest a model where variable amounts of β-defensin expression by mucosal cells, due to gene copy number variation, alters the efficacy of recruitment of Th17 lymphocytes to the site of infection, altering the dynamics of infection.

Editorial Commentary: Advocating the Concept of GB Virus C Biotherapy Against AIDS

Editorial Commentary: Advocating the Concept of GB Virus C Biotherapy Against AIDS

Immunogenicity, Immunologic Memory, and Safety Following Measles Revaccination in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy

Response rates and immunologic memory following measles vaccination are reduced in human immunodeficiency virus (HIV)-infected children in the absence of highly active antiretroviral therapy (HAART). HIV-infected children 2 to <19 years old receiving HAART and with HIV loads <30,000 copies/mL, CD4% ≥15, and ≥1 prior measles-mumps-rubella vaccination (MMR) were given another MMR. Measles antibody concentrations before and 8, 32, and 80 weeks postvaccination were determined by plaque reduction neutralization (PRN). A subset was given another MMR 4-5 years later, and PRN antibody was measured before and 7 and 28 days later. At entry, 52% of 193 subjects were seroprotected (PRN ≥120 mIU/mL). Seroprotection increased to 89% 8 weeks postvaccination, and remained at 80% 80 weeks postvaccination. Of 65 subjects revaccinated 4-5 years later, 85% demonstrated memory based on seroprotection before or 7 days after vaccination. HIV load ≤400 copies/mL at initial study vaccination was associated with higher seroprotection rates, greater antibody concentrations, and memory. Grade 3 fever or fatigue occurred in 2% of subjects. Measles revaccination induced high rates of seroprotection and memory in children receiving HAART. Both endpoints were associated with HIV viral load suppression. NCT00013871 (www.clinicaltrials.gov).

Role of the Veterans Aging Cohort Study Index in Assessing Total Atherosclerotic Burden

To the Editor—We read with great interest the study by Justice et al in which they build upon their prior work by incorporating inflammatory markers (sCD14 and D-dimer) into the Veterans Aging Cohort Study (VACS) index in order to improve its predictive accuracy for mortality [1, 2]. Cardiovascular disease (CVD) deaths are an important cause of mortality in human immunodeficiency virus (HIV)–infected patients, and thus it is notable that none of the components of the VACS index represent CVD risk factors. We therefore explored the use of the VACS index in assessing CVD burden using coronary artery calcium (CAC) scores, a validated surrogate marker of CVD events [3], as the response variable. Additionally, we assessed whether additional inflammatory molecules and endothelial dysfunction markers might modify this association. We utilized the Hawaii Aging with HIV–Cardiovascular Study cohort, a longitudinal study of the role of oxidative stress and inflammation in HIV cardiovascular risk. Univariate logistic regression models were used to estimate odds ratios for the association between CAC scores (presence/absence) and VACS index and components of VACS index (Table 1). A significant association between the VACS index and presence of CAC was observed (P <.01). When the VACS was broken down to its components (age, current CD4 count, HIV RNA, hemoglobin, FIB-4, eGFR, and coinfection with hepatitis C), only age correlated with CAC scores. When both VACS index and age were included in the model, P values of the Wald test for age and VACS index were <.01 and .47, respectively, suggesting that age is relatively more important than the VACS index in association with the CAC score. Lastly, we assessed the association between the following inflammatory molecules and endothelial dysfunction markers and the VACS index: soluble adhesion molecules (sICAM-1, sVCAM-1), soluble E-selectin, plasminogen activator inhibitor 1, tumor necrosis factor α, monocyte chemotactic protein 1, and c-reactive protein. No association was found between these biomarkers and the VACS index. Table 1. Association of Veterans Aging Cohort Study Index and Its Components With Coronary Artery Calcium This study is limited by its reliance on a surrogate marker of CVD rather than on clinical outcomes. Our cohort differs from the VACS cohort ethnically and by its composition predominantly of nonveterans. All our subjects were on stable antiretroviral therapy, and 85% of them had an undetectable HIV load. Despite these differences, our findings have important implications and suggestions for future research. Our data demonstrate that, although the VACS index correlates with CAC scores, a validated surrogate marker of CVD risk, this association is exclusively driven by age. Whether or not the other components of the VACS index are useful to predict CVD mortality as a subset of all-cause mortality is uncertain. In order to better refine the utility of the VACS index, it will be critical to assess its association with cause-specific mortality, including CVD mortality.

Clinical Manifestations of Human Immunodeficiency Virus-Induced Uveitis

To describe the clinical manifestations of patients with human immunodeficiency virus (HIV)-induced uveitis in Thailand. Prospective cohort study of 6 patients with HIV-induced uveitis. Six patients (8 eyes) with HIV-induced uveitis who had an extremely high intraocular: plasma HIV-1 RNA ratio. The clinical manifestations and laboratory findings are reported of 6 consecutive patients with HIV-induced uveitis who had an extremely high intraocular-to-plasma HIV-1 RNA ratio and were diagnosed between July 2009 and May 2011. Clinical manifestations and laboratory findings. Human immunodeficiency virus-induced uveitis was diagnosed in 4 men and 2 women with an average age of 41 years at presentation. None of the patients were receiving highly active anti-retroviral therapy (HAART) or had clinical or laboratory evidence, or both, of opportunistic infections. The mean plasma load was 218 688 copies/ml (median, 137 500 copies/ml; range, 24 900-540 000 copies/ml), and the mean intraocular HIV load was 20 937 755 copies/ml (median, 7 499 000 copies/ml; range, 2 460 000-89 800 000 copies/ml). The average CD4 cell count was 192 cells/μl (median, 248 cells/μl; range, 5-342 cells/μl). All the patients had decreased vision, and none had conjunctival hyperemia. The anatomic location of uveitis was anterior in all patients, and associated vitreitis was present in 4 patients; none exhibited retinal lesions or scars. Anterior segment inflammation and keratic precipitates were observed in all patients, and none responded to topical corticosteroid therapy. After the administration of HAART, the intraocular inflammation disappeared entirely within several weeks in all of the patients and the intraocular and plasma HIV loads decreased. Human immunodeficiency virus-induced uveitis should be suspected in HAART-naïve, HIV-positive patients or in those in whom this treatment fails and who have anterior uveitis without any retinal lesions and exhibit no response to topical corticosteroids. The concurrent determination of HIV load in the intraocular fluids and plasma may clarify the cause of HIV-associated uveitis.