Human Immunodeficiency Virus Type 1 Infected Individuals Research Articles

Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: the AGEhIV cohort study.

Human immunodeficiency virus (HIV)-infected individuals may be at increased risk of age-associated noncommunicable comorbidities (AANCCs). Cross-sectional analyses of AANCC prevalence (including cardiovascular, metabolic, pulmonary, renal, bone, and malignant disease) and risk factors in a prospective cohort study of HIV type 1-infected individuals and HIV-uninfected controls, who were aged ≥45 years and comparable regarding most lifestyle and demographic factors. HIV-infected participants (n = 540) had a significantly higher mean number of AANCCs than controls (n = 524) (1.3 [SD, 1.14] vs 1.0 [SD, 0.95]; P < .001), with significantly more HIV-infected participants having ≥1 AANCC (69.4% vs 61.8%; P = .009). Hypertension, myocardial infarction, peripheral arterial disease, and impaired renal function were significantly more prevalent among HIV-infected participants. Risk of AANCC by ordinal logistic regression was independently associated with age, smoking, positive family history for cardiovascular/metabolic disease, and higher waist-to-hip ratio, but also with HIV infection (odds ratio, 1.58 [95% confidence interval, 1.23-2.03]; P < .001). In those with HIV, longer exposure to CD4 counts <200 cells/µL, and, to a lesser extent, higher levels of high-sensitivity C-reactive protein and soluble CD14, and longer prior use of high-dose ritonavir (≥400 mg/24 hours) were each also associated with a higher risk of AANCCs. All AANCCs were numerically more prevalent, with peripheral arterial, cardiovascular disease, and impaired renal function significantly so, among HIV-infected participants compared with HIV-uninfected controls. Besides recognized cardiovascular risk factors, HIV infection and longer time spent with severe immunodeficiency increased the risk of a higher composite AANCC burden. There was a less pronounced contribution from residual inflammation, immune activation, and prior high-dose ritonavir use.

High Frequency of Non-B Human Immunodeficiency Virus Type 1 (HIV-1) Subtype Specific Mutations at the Protease Gene among Treatment-naive HIV-1 Infected Individuals in Jos, Nigeria

AIDS Prevention Initiative in Nigeria Department, Jos University Teaching Hospital, Jos, Nigeria. HIV-research Laboratory, Kenya Medical Research Institute, Kisumu, Kenya. Department of Pediatrics, University of Jos, Jos, Nigeria. Department Medicine, University of Jos, Jos, Nigeria. Department Family Medicine, University of Jos, Jos Nigeria. Medical Research Council Unit, Fajara, Banjul, The Gambia. Department of Obstetrics and Gynaecology University of Jos, Jos, Nigeria. Department of Microbiology, Ahmadu Bello University Zaria, Nigeria. Department of Medical Laboratory Science, University of Jos, Nigeria. Director General, National Agency for Control of AIDS, Abuja, Nigeria.

Human Paraoxonase-1 Activity Is Related to the Number of CD4+ T-Cells and Is Restored by Antiretroviral Therapy in HIV-1-Infected Individuals

Background. Paraoxonase-1 (PON1) activity is suggested to be altered in individuals infected with human immunodeficiency virus type-1 (HIV-1). We investigated PON1 activity in individuals receiving different regimens of highly active antiretroviral therapy (HAART). Methods. PON1 activity was evaluated in 91 HIV-1 seronegative and 624 HIV-1 infected individuals (115 were not undergoing therapy (ART-naïve), and 509 were receiving HAART). HIV-1 infected individuals were treated with the following: efavirenz (EFV; n = 195) or nevirapine (NVP; n = 95) or lopinavir/ritonavir (LOP/r; n = 219). Serum levels of total cholesterol (TC), HDL, and low-density lipoprotein (LDL) fractions and the atherogenic indices (AI, TC : HDL, and LDL : HDL ratios) were determined. Results. PON1 activity (U/L) was lower in the ART-naïve group compared with the other groups. PON1 activity correlated with CD4+ T-cell number of ART-naïve group (r = 0,121; P = 0,014). The LOP/r group showed a reduction in HDL and an increase in AI (TC : HDL ratio) in comparison with other groups. Conclusion. PON1 activity was reduced in untreated individuals, but not in individuals receiving HAART. PON1 activity correlated with the number of CD4+ T-cells. The findings suggest that the activity of PON1 is associated with the immune status of HIV-1 infected individuals.

Association between inbreeding coefficient and susceptibility to HIV-1 infection, a case-control study

Consanguinity has been associated with adverse health outcomes. The objective of the present study was to assess the association between parental consanguinity and risk of infection with human immunodeficiency virus type-1 (HIV-1). Data were collected from 333 HIV-1 infected individuals referred to a local health center in Shiraz (southern Iran). A total of 999 healthy individuals frequency matched with the cases according to their sex and age were also studied, as a control group. Prevalence of parental consanguineous marriage was 23.7% and 32.8% among patients and controls, respectively (Chi(2)=9.880, df=1, p=0.007). The mean inbreeding coefficient was 0.0110 and 0.0156 among patients and controls, respectively. The risk of infection with HIV-1 decreased as a function of inbreeding coefficient (Chi(2)=7.531, p=0.006). The present finding indicates a negative association between the susceptibility of HIV-1 infection and the inbreeding coefficient.

HIV-1 Transmission Networks in a Small World

HIV-1 Transmission Networks in a Small World

Gastrointestinal Viral Load and Enteroendocrine Cell Number Are Associated with Altered Survival in HIV-1 Infected Individuals

Human immunodeficiency virus type 1 (HIV-1) infects and destroys cells of the immune system leading to an overt immune deficiency known as HIV acquired immunodeficiency syndrome (HIV/AIDS). The gut associated lymphoid tissue is one of the major lymphoid tissues targeted by HIV-1, and is considered a reservoir for HIV-1 replication and of major importance in CD4+ T-cell depletion. In addition to immunodeficiency, HIV-1 infection also directly causes gastrointestinal (GI) dysfunction, also known as HIV enteropathy. This enteropathy can manifest itself as many pathological changes in the GI tract. The objective of this study was to determine the association of gut HIV-1 infection markers with long-term survival in a cohort of men who have sex with men (MSM) enrolled pre-HAART (Highly Active Antiretroviral Therapy). We examined survival over 15-years in a cohort of 42 HIV-infected cases: In addition to CD4+ T cell counts and HIV-1 plasma viral load, multiple gut compartment (duodenum and colon) biopsies were taken by endoscopy every 6 months during the initial 3-year period. HIV-1 was cultured from tissues and phenotyped and viral loads in the gut tissues were determined. Moreover, the tissues were subjected to an extensive assessment of enteroendocrine cell distribution and pathology. The collected data was used for survival analyses, which showed that patients with higher gut tissue viral load levels had a significantly worse survival prognosis. Moreover, lower numbers of serotonin (duodenum) and somatostatin (duodenum and colon) immunoreactive cell counts in the gut tissues of patients was associated with significant lower survival prognosis. Our study, suggested that HIV-1 pathogenesis and survival prognosis is associated with altered enteroendocrine cell numbers, which could point to a potential role for enteroendocrine function in HIV infection and pathogenesis.

Calcitonin gene–related peptide inhibits Langerhans cell–mediated HIV-1 transmission

Upon its mucosal entry, human immunodeficiency virus type 1 (HIV-1) is internalized by Langerhans cells (LCs) in stratified epithelia and transferred locally to T cells. In such epithelia, LCs are in direct contact with peripheral neurons secreting calcitonin gene-related peptide (CGRP). Although CGRP has immunomodulatory effects on LC functions, its potential influence on the interactions between LCs and HIV-1 is unknown. We show that CGRP acts via its receptor expressed by LCs and interferes with multiple steps of LC-mediated HIV-1 transmission. CGRP increases langerin expression, decreases selected integrins, and activates NF-κB, resulting in decreased HIV-1 intracellular content, limited formation of LC-T cell conjugates, and elevated secretion of the CCR5-binding chemokine CCL3/MIP-1α. These mechanisms cooperate to efficiently inhibit HIV-1 transfer from LCs to T cells and T cell infection. In vivo, HIV-1 infection decreases CGRP plasma levels in both vaginally SHIV-challenged macaques and HIV-1-infected individuals. CGRP plasma levels return to baseline after highly active antiretroviral therapy. Our results reveal a novel path by which a peripheral neuropeptide acts at the molecular and cellular levels to limit mucosal HIV-1 transmission and suggest that CGRP receptor agonists might be used therapeutically against HIV-1.

Detection of Low-Frequency HIV Type 1 Reverse Transcriptase Drug Resistance Mutations by Ultradeep Sequencing in Naive HIV Type 1-Infected individuals

Genotypic resistance testing is recommended to evaluate the susceptibility of HIV to antiretroviral drugs. These tests are based on bulk population sequencing and thus consider only variants representing more than 20% of the viral population, whereas next generation sequencing methods allow detection below this threshold. We aimed to evaluate the potential use of ultradeep pyrosequencing (UDPS) for genotypic resistance testing in clinical routine at the University Hospital of Bordeaux, France. We performed UDPS on reverse transcriptase (RT) from 47 HIV-1 individuals, naive of antiretroviral treatment and for whom genotypic resistance testing was requested for clinical management in 2011-2012. In 8.5% of the patients, only low-frequency variants harboring RT drug resistance mutations were detected raising the question of their clinical significance. Rilpivirine-associated resistance mutations were detected in 19.1% of our population study. To conclude, UDPS could become a routine tool for the evaluation of HIV-infected patients in hospital laboratories.

Reversion and Conversion of Interferon-γ Release Assay Results in HIV-1–Infected Individuals

In this prospective study, human immunodeficiency virus type 1 (HIV-1)-infected subjects underwent QuantiFERON-TB Gold In-Tube interferon-γ release assay (IGRA) testing at baseline and after 24 months in a low tuberculosis incidence country. Concordant baseline and follow-up results were observed in 86% (n = 686 of 794) of subjects. IGRA conversions occurred in 9% (n = 63 of 718), whereas IGRA reversions were seen in 33% (n = 25 of 76) of individuals. Of the 10 active tuberculosis cases during follow-up, 5 had concordant positive IGRA results and 2 were IGRA converters. Although the clinical significance of IGRA conversions and reversions remains to be established, repeated IGRA testing seems to be of value in HIV-1-infected individuals.

Plasmacytoid Dendritic Cell Number and Responses to Toll-Like Receptor 7 and 9 Agonists Vary in HIV Type 1-Infected Individuals in Relation to Clinical State

In HIV-1 infection, plasmacytoid dendritic cell (PDC) numbers and function are decreased. No detailed comparisons of PDC responses to various stimuli in HIV-1-infected patients are available. Using for the first time purified PDCs, we compared PDC responses [interferon (IFN)-α production/cell] to various stimuli in a large number (n=48) of HIV-1-infected patients and healthy volunteers (n=19). Toll-like receptor (TLR)7- and TLR9-induced expression of PDC surface activation and maturation markers was also compared in the two populations. We have confirmed that PDC number coincides with CD4(+) T cell counts and clinical state. Notably, we have shown that a direct association of PDC function in terms of IFN-α production/cell exists with PDC numbers and CD4(+) cell counts when PDCs are exposed to a TLR9 ligand and HIV-infected cells, but not with a TLR7 ligand. Moreover, in the HIV-infected subjects but not the healthy controls, the magnitude of IFN-α release per PDC in response to the TLR7 ligand is significantly (p<0.01) lower than that to the TLR9 ligand. However, in both study populations, the TLR7 stimulation in comparison to TLR9 stimulation induced higher expression of PDC surface activation and maturation markers and significantly (p<0.05) decreased the expression of BDCA-2, a negative regulator of interferon. Furthermore, the cross-ligation of BDCA-2 significantly (p<0.05) inhibited TLR9- but not TLR7-induced IFN-α production by PDCs from both clinical groups. These findings suggest that differences exist in TLR7- and TLR9-induced IFN-α production by PDCs in HIV-infected individuals that are not directly related to BDCA-2 down-modulation.

A technique for capturing broad subtypes and circulating recombinant forms of HIV-1 based on anionic polymer-coated magnetic beads

Magnetic beads coated with an anionic polymer, poly(methyl vinyl ether-maleic anhydrate) [poly(MVE-MA)], were used in a method to capture human immunodeficiency virus type-1 (HIV-1). The beads were incubated with either HIV-1-infected cell culture medium or plasma from HIV-1 infected individuals and separated from the supernatant by applying a magnetic field. After thorough washing, adsorption of HIV-1 by the beads was confirmed by reverse transcription (RT)-polymerase chain reaction (PCR), real-time PCR, enzyme-linked immunosorbent assay and western blotting. The results confirmed the presence of envelope, polymerase, Nef and the viral genome of HIV-1. Furthermore, various subtypes and circulating recombinant forms (CRFs) of HIV-1 including subtype B, C and CRF01_AE and the immature form of subtype B HIV-1 could be captured. Preincubation with neutralizing antibody against HIV-1 envelope gp41 decreased the capture efficiently, suggesting that poly(MVE-MA) binds HIV-1 via gp41. We believe that this capture procedure will be a valuable tool for detecting various types of HIV-1 in both clinical and experimental samples.

Short Communication: Human Lymphotropic Virus Type 1 Coinfection Modulates the Synthesis of Cytokines by Peripheral Blood Mononuclear Cells from HIV Type 1-Infected Individuals

HIV-1 and HTLV-1 infect CD4(+) T lymphocyte but little is known about the impact of coinfection on patient's immune response. In this study we have evaluated the spontaneous production of interleukin (IL)-2, IL-4, IL-6, and IL-10 and interferon (IFN)-γ by unstimulated peripheral blood mononuclear cell (PBMC) cultures obtained from patients infected by HTLV-1, HIV-1, or both viruses. We have observed that HIV/HTLV-coinfected individuals presented significantly higher production of IL-2 and IFN-γ compared to both HIV single-infected and HTLV single-infected individuals. IL-6 and IL-10 synthesis was similar in all infected groups, but HTLV single-infected individuals presented a lower production of IL-4. These results show that HIV/HTLV-coinfected individuals presented a profile of higher production of Th-1 cytokines, suggesting a predominant stimulus of HTLV-1 in detriment to HIV-1 infection.

Preserved Function of Regulatory T Cells in Chronic HIV-1 Infection Despite Decreased Numbers in Blood and Tissue

Regulatory T cells (Tregs) are potent immune modulators, but their role in human immunodeficiency virus type 1 (HIV-1) pathogenesis remains poorly understood. We performed a detailed analysis of the frequency and function of Tregs in a large cohort of HIV-1-infected individuals and HIV-1 negative controls. While HIV "elite controllers" and uninfected individuals had similar Treg numbers and frequencies, the absolute numbers of Tregs declined in blood and gut-associated lymphoid tissue in patients with chronic progressive HIV-1 infection. Despite quantitative changes in Tregs, HIV-1 infection was not associated with an impairment of ex vivo suppressive function of flow-sorted Tregs in both HIV controllers and untreated chronic progressors.

Prevalence of hepatitis C virus infection and human immunodeficiency virus in a cohort of Egyptian hemophiliac children

BACKGROUND AND OBJECTIVEThe risk of blood-borne infections, especially hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection still remains in developing countries among children receiving blood products as hemophiliacs, but the risk is not known in Egypt. The objective of this study was to detect the prevalence of HCV and HIV infection among hemophiliac children to know the magnitude of the problem and determine potential risk factors.PATIENTS AND METHODSThis was a cross-sectional study conducted on 100 hemophiliac children that assessed the liver clinically and by laboratory tests. All children were screened for HCV and HIV antibodies by enzyme-linked immunosorbent assay. Those with positive HCV antibody titre were tested by polymerase chain reaction (HCV-PCR).RESULTSForty were positive for HCV antibodies with 19 children (47.5%) HCV-PCR positive as well. The mean age, average frequency of bleeds/year, dose of replacement therapy/year and alanine aminotransferase (ALT) levels were significantly high in HCV-antibody and PCR positive patients as compared to HCV antibody and PCR negative ones. None of our patients had clinical evidence of hepatic involvement or was co-infected with HIV.CONCLUSIONHIV infection does not appear to be a current health problem in Egyptian hemophiliac children though the prevalence of HCV infection is still high.

Prevalence of occult hepatitis B amongst Indian human immunodeficiency virus type 1 infected individuals—a pilot study

BackgroundThe diagnosis of hepatitis B is routinely based on the detection of hepatitis B surface antigen (HBsAg) only. However, occult hepatitis B virus (HBV) infection (OBI), which is defined as infection with positive hepatitis B core antibody (anti-HBc) antibodies, positive DNA (deoxyribonucleic acid) PCR (polymerase chain reaction), and undetectable HBsAg, as well as anti-HBs antibodies in serum or plasma of HBV infected individuals, will remain undetected using this screening diagnostic approach of detecting HBsAg. The current study aims in studying the prevalence of the OBI amongst human immunodeficiency virus type 1 (HIV-1) infected individuals who have not been exposed to anti-retroviral therapy. MethodEstimation of HBsAg, anti-HBs, and anti-HBc total antibody status amongst 100 HIV-1 infected study participants was carried out using enzyme-linked immunosorbent assay (ELISA) kits. Detection of HBV-DNA was carried out by in-house qualitative PCR. CD4 + T lymphocyte counts were analysed using Becton Dickinson's (BD) FACSCount™ system. ResultsThe median age of the HIV-1 infected study population was 35 years (range: 22–67), with the gender distribution being 53 males and 47 females. The mean CD4 T lymphocyte count of the study participants was 210/mm3. Overall, serological evidence of HBV infection was observed in 28% of the HIV-1 infected study participants. There was 5% seropositivity for HBsAg, of which 2% were additionally positive for HBV-DNA-PCR. “Anti-HBc alone” status was seen in 18% of study participants, this being statistically higher in those with CD4 T lymphocyte counts < 200/mm3. While there was a single specimen with co-positivity for anti-HBc total antibodies and HBV-DNA, 5% of the in the study population exhibited anti-HBs antibodies positivity, with one sample exhibiting dual positivity for HBsAg and anti-HBs antibodies. ConclusionOccult HBV infections may contribute to chronic liver damage, and associ-ated reactivation amongst immunocompromised individuals, HIV-1 in-fected being a subset of them. “Anti-HBc” testing followed by HBV-DNA detection by PCR can be utilised for such populations to detect OBIs. Early detection of hepatitis B viraemia will be important for deciding the antiviral therapeutic protocol so as to avoid evolution of antiviral resistance in the circulating HBV strains in HIV-1 infected individuals harbouring OBIs.

The Setpoint Study (ACTG A5217): Effect of Immediate Versus Deferred Antiretroviral Therapy on Virologic Set Point in Recently HIV-1–Infected Individuals

The benefits of antiretroviral therapy during early human immunodeficiency virus type 1 (HIV-1) infection remain unproved. A5217 study team randomized patients within 6 months of HIV-1 seroconversion to receive either 36 weeks of antiretrovirals (immediate treatment [IT]) or no treatment (deferred treatment [DT]). Patients were to start or restart antiretroviral therapy if they met predefined criteria. The primary end point was a composite of requiring treatment or retreatment and the log(10) HIV-1 RNA level at week 72 (both groups) and 36 (DT group). At the June 2009 Data Safety Monitoring Board (DSMB) review, 130 of 150 targeted participants had enrolled. Efficacy analysis included 79 individuals randomized ≥72 weeks previously. For the primary end point, the IT group at week 72 had a better outcome than the DT group at week 72 (P = .005) and the DT group at week 36 (P = .002). The differences were primarily due to the higher rate of progression to needing treatment in the DT group (50%) versus the IT (10%) group. The DSMB recommended stopping the study because further follow-up was unlikely to change these findings. Progression to meeting criteria for antiretroviral initiation in the DT group occurred more frequently than anticipated, limiting the ability to evaluate virologic set point. Antiretrovirals during early HIV-1 infection modestly delayed the need for subsequent treatment. NCT00090779.

Semen of HIV-1–Infected Individuals: Local Shedding of Herpesviruses and Reprogrammed Cytokine Network

Semen is the main carrier of sexually transmitted viruses, including human immunodeficiency virus type 1 (HIV-1). However, semen is not just a mere passive transporter of virions but also plays an active role in HIV-1 transmission through cytokines and other biological factors. To study the relationship between viruses and the chemokine-cytokine network in the male genital tract, we measured the concentrations of 21 cytokines/chemokines and the loads of HIV-1 and of 6 herpesviruses in seminal and blood plasma from HIV-1-infected and HIV-uninfected men. We found that (1) semen is enriched in cytokines and chemokines that play key roles in HIV-1 infection or transmission; (2) HIV-1 infection changes the chemokine-cytokine network in semen, further enriching it in cytokines that modulate its replication; (3) HIV-1 infection is associated with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) compartmentalized seminal reactivation; (4) CMV and EBV concomitant seminal shedding is associated with higher HIV-1 loads in blood and seminal plasma; and (5) CMV seminal reactivation increases the seminal levels of the CCR5 ligands RANTES and eotaxin, and of the CXCR3 ligand monokine induced by gamma interferon (MIG). HIV-1 infection results in an aberrant production of cytokines and reactivation of EBV and CMV that further changes the seminal cytokine network. The altered seminal milieu in HIV-1 infection may be a determinant of HIV-1 sexual transmission.

The Vpr Gene Polymorphism of Human Immunodeficiency Virus Type 1 in China and its Clinical Significance

Recent studies have explored that mutated Human immunodeficiency virus type 1(HIV-1) Vpr genes likely influence clinical manifestations of HIV infected patients. However, the relationship between the mutation sites on HIV Vpr gene and subsequent function changes is still not clear. In this study we investigated such relationship in analyzing the Vpr genes of HIV-1 viruses isolated from 208 HIV-1 infected patients from different regions in China. Reverse transcription polymerase chain reaction (RT-PCR) and nested PCR were used to amplify HIV-1 Vpr gene extracted from plasma of 208 HIV-1 infected patients and 153 isolates displayed the target gene sequences. Biological analysis software analyzed the deduced amino acid sequence, and identified the characteristics of the polymorphism of HIV-1 Vpr gene and its clinical significance. Results show the sequence subtypes as follows: CRF01-AE is 51.63%, subtype C is 24.84%, ubtype B is 17.65%, CRF03-AB is 3.92% and CRF08-BC is 1.31%. This paper revealed for the first time the HIV-1 Vpr gene polymorphism in HIV-1 positive individuals in China.: the subtype CRF01-AE is the main Vpr gene subtype in this region. The mutations in the C-terminal were more obvious than those observed in the N-terminal. It was also discovered that in the 77th position, 84.3% of the 153 amino acid sequences were glutamine (Q), which differ from overseas reports. Our data showed that the mutations 63, 70, 85, 86, 89 and 94 of the Vpr gene were possibly correlated with the clinical manifestations of the HIV-1 infected individuals.

Antiplatelet Activity of Valproic Acid Contributes to Decreased Soluble CD40 Ligand Production in HIV Type 1-Infected Individuals

CD40L is a type II membrane glycoprotein of the TNF family that is found on activated T cells, B cells, and platelets. We previously reported that the soluble form of this inflammatory mediator (sCD40L) is elevated in the plasma and cerebrospinal fluid of HIV-1-infected, cognitively impaired individuals. In this study, we demonstrate that the mood-stabilizing drug valproic acid (VPA) reduces sCD40L levels in plasma samples of HIV-1-infected patients (n = 23) and in washed human platelets, which are the main source of circulating sCD40L. VPA also inhibited HIV-1 transactivator of transcription-induced release of sCD40L and platelet factor 4 in C57BL/6 mice. The mechanism by which VPA was able to do so was investigated, and we demonstrate that VPA, a known glycogen synthase kinase 3β inhibitor, blocks platelet activating factor-induced activation of glycogen synthase kinase 3β in platelets in a manner that alters sCD40L release from platelets. These data reveal that VPA has antiplatelet activity, and they convey important implications for the potential of VPA as an adjunct therapy not only for cognitively impaired patients with HIV-1 infection, but also numerous inflammatory diseases for which such antiplatelet therapies are currently lacking.

Preconditioning, postconditioning, stunning and hibernation: Towards an integrated insight into the mechanisms of hypoperfusion/reperfusion

2006;64:226–33. [12] Mehta S, Giovannucci E, Mugusi FM, et al. Vitamin D status of HIV-infected women and its association with HIV disease progression, anemia, and mortality. PLoS ONE 2010;5:e8770. [13] Mueller NJ, Fux CA, Ledergerber B, et al, Swiss HIV Cohort Study. High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated Swiss HIV patients. AIDS 2010;24:1127–34. [14] Bang UC, Shakar SA, HitzMF, et al. Deficiency of 25-hydroxyvitamin D inmale HIVpositive patients: a descriptive cross-sectional study. Scand J Infect Dis 2010;42:306–10. [15] Van Den Bout-Van Den Beukel CJ, Fievez L, Michels M, et al. Vitamin D deficiency among HIV type 1-infected individuals in the Netherlands: effects of antiretroviral therapy. AIDS Res Hum Retroviruses 2008;24:1375–82. [16] MelamedML, Michos ED, PostW, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med 2008;168:1629–37. [17] Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med 2008;168:1174–80. [18] Shewan LG, Coats AJ. Ethics in the authorship and publishing of scientific articles. Int J Cardiol 2010;144:1–2. [19] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.