Role Of HIV Research Articles

Maternal mortality ratio - trends in the vital registration data

Background. The paucity of quality data on maternal deaths and possible mis-specification of models have resulted in a range of estimates of the maternal mortality ratio (MMR) for South Africa. Objectives. This paper contrasts the estimates from multi-country models for estimating the MMR with the South African data from vital registration. Method. A literature review was undertaken to identify estimates of the MMR for South Africa and methodologies used. In addition, cause of death data from Statistics SA were analysed for trends. Results. In contrast to prediction models used by international agencies, the Health Data Advisory and Co-ordinating Committee (HDACC) recommended the use of the vital registration data adjusted for under-registration and misclassification of causes to monitor maternal mortality. HADCC also recommended that, as is done by the Maternal Mortality Estimation Interagency Group (MMEIG), the number of maternal deaths identified be scaled up by 50% to account for the general under-reporting of maternal deaths. Based on this approach, the baseline MMR in 2008 was estimated to be 310 per 100 000 live births. From vital statistics, the indications are that by 2009, South Africa had not yet managed to reverse the upward trend in MMR. The increase is largely a result of an increase in the number of maternal deaths from indirect causes, as might be expected in the context of the HIV pandemic. However, the number of indirect maternal deaths increased markedly only since 2003, a few years later than the rapid increase in AIDS mortality. Conclusions. There are opportunities to improve monitoring maternal mortality, including strengthening the information systems (vital registration, the confidential enquiry and the routine health information system) and exploring opportunities for linking data from different sources. Better data on the role of HIV in maternal mortality are needed.

Role of FAP48 in HIV-associated lipodystrophy

The introduction of highly active antiretroviral therapies (HAART) has significantly changed the clinical course of HIV disease, with prolonged survival and better quality of life for HIV infected patients. However, this successful therapeutic advance has been partially marked by the development of serious long-term side effects including metabolic alterations, cardiovascular disease, kidney impairment, bone alterations and adipose tissue redistribution. This last phenomenon is currently indicated as HIV related lipodystrophy (Barbaro, 2006). Even if some studies suggested an independent role for HIV in the development of lipodystrophic phenotype, there is a widely accepted consensus that the risk to develop fat redistribution in HIV patients has to be mostly related to antiretroviral therapy. In order to investigate new pathways involved in the development of lipodystrophy, our group performed an array screening using two identical filter arrays with cDNAlabeled probes, generated from the adipose tissue of either HIV patients affected or not affected by lipodystrophy. Among the genes selected, we focused our attention on a recently described 48 kDa protein of 417 amino acids named FAP48. Our results suggest, using 3T3-L1-FAP48 stable clone, that FAP48 over-expression results in rapid NFAT dephosphorilatyon by activating CaN and in the increase of aP2 gene transcription, a gene expressed at the last phase of the adipocyte differentiation. These data support the role of Fap48 in the activation of adipocyte differentiation through a pathway involving NFAT. Moreover we evaluated the expression of PPARγ and aP2 in 3T3-L1 FAP48pcDNA stably transfected cells treated with five antiretroviral drugs (Indinavir, Amprenavir, Efavirenz, Stavudine and Saquinavir), belonging to the three main classes of anti-HIV drugs, that were able, in our experimental model, to affect adipocyte differentiation (Esposito et al., 2009). We observed that cells treated with Saquinavir and Efavirenz, using 3T3-L1- FAP48 stable clone, are characterized by an increased expression of PPARγ and aP2, during the 6 day time course, compared with the control cells. This evidence supports the hypothesis of a protective mechanism, that in 3T3L1 cells could counteract the toxicity of Efavirenz and Saquinavir or could be activated in presence of these drugs. Drawing from our experimental results it can be then postulated that this mechanism could work trough FAP48/ FBP52/Hsp90 pathway, suggesting this complex as a potential target for novel therapeutic approaches to the HAART related lipodystrophy in patients treated with regimen including Efavirenz and Saquinavir.

CCL2: A potential prognostic marker and target of anti‐inflammatory strategy in HIV/AIDS pathogenesis

Chemokines are critical components of the immune system that participate in immune homeostasis and alterations in chemokine balance can result in severe inflammatory and autoimmune diseases. The role of chemokines and their receptors in viral infections including HIV-1 was predicted from the early studies of HIV-1 co-receptor CCR5 and its ligands and a divergent role of C-C chemokines in HIV-1 pathogenesis has been established. For example, CCL3 (MIP-1α), CCL4 (MIP-1β) and CCL5 (RANTES) have been shown to possess antiviral effects by binding to the HIV-1 co-receptor CCR5, whereas CCL2, a pro-inflammatory chemokine, supports HIV-1 replication despite being a member of same chemokine family. Furthermore, the well-established role of CCL2 in driving the Th2 immune response supports its potential role in HIV-1/AIDS. Recent reports suggest multiple pathways of CCL2 affect HIV-1 infection. In this review, we provide a comprehensive overview of the role and potential mechanisms of the HIV-1-CCL2 interplay in driving virus-induced immuno-pathology, suggesting that CCL2 could be an anti-inflammatory target in the treatment of HIV-1 infection.

IL-23 in Infections, Inflammation, Autoimmunity and Cancer: Possible Role in HIV-1 and AIDS

The growing family of interleukin (IL)-12-like cytokines produced by activated macrophages and dendritic cells became the important players in the control of infections, development of inflammation, autoimmunity and cancer. However, the role of one of them-heterodimer IL-23, which consists of IL12p40 and the unique p19 subunit in HIV-1 infection pathogenesis and progression to AIDS, represent special interest. We overviewed findings of IL-23 involvement in control of peripheral bacterial pathogens and opportunistic infection, central nervous system (CNS) viral infections and autoimmune disorders, and tumorogenesis, which potentially could be applicable to HIV-1 and AIDS.

Diabetes is a risk factor for pulmonary tuberculosis: a case-control study from Mwanza, Tanzania.

BackgroundDiabetes and TB are associated, and diabetes is increasingly common in low-income countries where tuberculosis (TB) is highly endemic. However, the role of diabetes for TB has not been assessed in populations where HIV is prevalent.MethodsA case-control study was conducted in an urban population in Tanzania among culture-confirmed pulmonary TB patients and non-TB neighbourhood controls. Participants were tested for diabetes according to WHO guidelines and serum concentrations of acute phase reactants were measured. The association between diabetes and TB, and the role of HIV as an effect modifier, were examined using logistic regression. Since blood glucose levels increase during the acute phase response, we adjusted for elevated serum acute phase reactants.ResultsAmong 803 cases and 350 controls the mean (SD) age was 34.8 (11.9) and 33.8 (12.0) years, and the prevalence of diabetes was 16.7% (95% CI: 14.2; 19.4) and 9.4% (6.6; 13.0), respectively. Diabetes was associated with TB (OR 2.2, 95% CI: 1.5; 3.4, p<0.001). However, the association depended on HIV status (interaction, p = 0.01) due to a stronger association among HIV uninfected (OR 4.2, 95% CI: 1.5; 11.6, p = 0.01) compared to HIV infected (OR 0.1, 95% CI: 0.01; 1.8, p = 0.13) after adjusting for age, sex, demographic factors and elevated serum acute phase reactants.ConclusionDiabetes is a risk factor for TB in HIV uninfected, whereas the association in HIV infected patients needs further study. The increasing diabetes prevalence may be a threat to TB control.

Factors contributing to impaired self-awareness of cognitive functioning in an HIV positive and at-risk population

Purpose: To examine the association between self-awareness of cognitive impairment and age, selected mood disorders, and type and severity of cognitive impairment in a sample of individuals with HIV/AIDS and at risk for HIV. Method: 75 subjects, 52 HIV+ and 23 at risk for HIV completed a psychosocial interview, the Patient’s Assessment of Own Functioning (PAOF) questionnaire, and a battery of neuropsychological tests. Based upon the differences between their clinical impairment and self-reported impairment, subjects were classified as being “Underestimators”, “Good Awareness”, or “Impaired Awareness” with regard to self-awareness. Results: Those with more severe cognitive impairment were less aware than those with normal or borderline cognitive impairment. A one-way ANOVA suggested that the Impaired Awareness group differed significantly from the Underestimators on the Rey Figure Immediate and Delayed Recall tasks, and from both the Underestimators and Good Awarenesss groups on the Digit Symbol Substitution Task. There were significant differences among all awareness groups on the test of Simple Reaction Time. Furthermore there is some suggestion that age may contribute to impaired self-awareness. The role of HIV in self-awareness remains unclear, as both, individuals with HIV and at risk, demonstrated impaired self-awareness. Conclusions: Overall, impaired awareness was associated with poorer test performance, suggesting a relationship between awareness and sustained complex attention and visual spatial processing. This research has implications for understanding factors contributing to poor awareness among individuals with cognitive impairment.Implications for RehabilitationImpaired self-awareness is associated with poor rehabilitation outcomes in populations with cognitive impairment.Individuals with and at risk for HIV/AIDS demonstrate cognitive impairments often associated with impaired self-awareness.Individuals with or at risk for HIV/AIDS have a critical need that could be addressed by rehabilitation professionals with expertise in assessing and treating impairments in self-awareness.

Imbalance between endothelial progenitors cells and microparticles in HIV-infected patients naive for antiretroviral therapy

Cardiovascular events have been reported among HIV-infected patients following antiretroviral therapy. However, the role of HIV itself in determining vascular damage is less described. Chronic inflammatory state might impair some regulatory endothelium properties leading to its activation, apoptosis or erosion. To evaluate the balance between endothelial progenitor cells and microparticles in HIV-infected antiretroviral drug-naive patients. A case-control study comparing HIV-infected patients (n = 35) with sex-matched and age-matched healthy controls (n = 33). Endothelial progenitor cells populations expressing CD34, CD133 and KDR were quantified by flow cytometry. Endothelial-derived microparticles, expressing CD51, and platelet-derived microparticles, expressing CD31/CD42, were also measured. Endothelial function was estimated by flow-mediated dilation. Lower percentages of endothelial progenitor cells (CD34/KDR) were observed in HIV-infected individuals compared with controls (0.02 vs. 0.09%, P = 0.045). In addition, endothelial microparticles concentration was higher in HIV-infected individuals (1963 vs. 436 microparticles/μl platelet-poor plasma, P = 0.003), with similar number of platelet-derived microparticles among groups. Furthermore, flow-mediated dilation was lower among HIV-infected individuals compared with controls [mean (SEM): 10 (1) and 16% (2), respectively; P = 0.03]. Our findings suggest an imbalance between endothelial progenitor cells mobilization and endothelial apoptosis. The alteration in the turnover of endothelial cells may contribute to cardiovascular events in HIV-infected patients.

Distributive sharing among HIV–HCV co-infected injecting drug users: the preventive role of trust in one's physician

This study, based on data from the MANIF 2000 cohort study, investigates the relationship between the lending of injecting equipment, drug use, and experience with HIV care. The sample comprised 224 HIV–HCV co-infected patients who reported having injected drugs in the previous six months and their 538 visits to clinical services. Longitudinal data were collected for medical status, and self-reported risk behaviors. A logistic regression GEE model was used to identify correlates of distributive sharing. After multiple adjustment, patients who reported trust in physicians were significantly less likely to report lending injection equipment while cocaine users were at increased risk. Promoting dialog between physicians and injecting drug users (IDUs) may play an important role in HIV–HCV positive prevention.

HIV-1 gp120 induces antioxidant response element-mediated expression in primary astrocytes: Role in HIV associated neurocognitive disorder

HIV infection affects the central nervous system resulting in HIV associated neurocognitive disorder (HAND), which is characterized by depression, behavioral and motor dysfunctions. The HIV-1 viral envelope protein gp120 is known to induce the release of neurotoxic factors which lead to apoptotic cell death. Although the exact mechanisms involved in HIV-1 gp120-induced neurotoxicity are not completely understood, oxidative stress is suggested to play a vital role in the neuropathogenesis of HAND. Astrocytes represent major population of the non-neuronal cell type in the brain and play a critical role in the neuropathogenesis of HAND. Increased oxidative stress is known to induce nuclear factor erythroid derived 2-related factor 2 (Nrf2), a basic leucine zipper transcription factor which is known to regulate the antioxidant defensive mechanism. However, the role of Nrf2 in HAND has not been elucidated. We report that gp120 significantly upregulates Nrf2 in human astrocytes and is associated with stimulation of key antioxidant defensive enzymes Hemoxygenase (HO-1) and NAD(P)H dehydrogenase quinone1 (Nqo1). Pretreatment of the astrocytes with antioxidants or a specific calcium chelator BAPTA-AM, significantly blocked the upregulation of Nrf2, HO-1 and Nqo1. These results suggest a possible role of the intracellular calcium and oxidative stress in Nrf2 mediated antioxidant defense mechanism, which may have protective role in promoting cell survival.

Detection of Hepatitis B Virus Variants in HBV Monoinfected and HBV/HIV Coinfected Iranian Patients Under Lamivudine Treatment

Chronic hepatitis B affects nearly 10% of HIV-infected patients. Hepatitis B virus (HBV) infection is a dynamic disease and coinfection with HIV impacts directly on the outcome of HBV infection, considerably complicating its natural history, diagnosis, and management. The aim of this study was to compare two cohorts of HBV monoinfected and HBV/HIV coinfected Iranian patients undergoing long-term lamivudine therapy from the clinical and virological aspects, as well as the frequency of detected mutations in HBV genome. To this end, HBV Pol/S regions from 72 patients were PCR-amplified and directly sequenced. Phylogenetic analysis indicated a 40-times higher risk of coinfection with ayw3 subtype of HBV genotype D rather than ayw2 subtype [P<0.001, odd: 40.66, CI: 95 % (4.69-352.23)]. While no resistance mutation was detected in HBV/HIV coinfected cohort, LAM-resistance mutations (rtM204I/V in YMDD and rtL180M in FLLA polymerase motifs) were identified in 30% (9 out of 30) and 16.66% (5 out of 30) of HBV monoinfected patients (P<0.05). Moreover, several mutations (sP105A, sI110S/L, sS136Y and sP127T/L) with significant differences in the frequency were identified in the S region of both cohorts. Finally, this study found strong correlation between the type of infection (mono or coinfection) and characteristics like patient gender, ALT levels, HBV-DNA levels and HBV subtypes. These results pointed to the importance of determination of HBV variants in the management of patients and suggested that in contrary to HBV monoinfections, LAM may be still an appropriate drug for the treatment of HBV in HBV/HIV coinfected patients; however, further studies to clarify the role of HIV in HBV LAM-resistance mutations are required.

HIV infection, body composition changes and related metabolic complications: contributing factors and evolving management strategies

Metabolic toxicities in HIV patients are common and contribute to clinical status and long-term sequelae. Body fat mass alterations, of multifactorial causes, continue to occur, despite use of antiretroviral drugs associated with fewer metabolic side-effects. The role of HIV itself in the development of these changes is being better defined and a deeper understanding of perturbations in intermediary metabolic processes is emerging. Treatment options are also being identified. HIV itself may be a direct causal factor in the accelerated atherosclerosis and decreased levels of high-density lipoprotein that occur and contribute to increased cardiovascular complications. Antiretroviral drug-related and inflammation-related effects can cause mitochondrial toxicity and are an emerging area of research. The association of increased visceral adipose tissue with both drug-related and chronic inflammation-related factors is now better understood. The role of accelerated aging as a paradigm is useful to understand long-term outcome risks for patients. The use of growth hormone-releasing factor as a viable treatment option for increased visceral abdominal tissue has recently been confirmed for selected patients. Metabolic issues persist in HIV patients who are otherwise stable. Understanding the various inter-related contributing factors has allowed for rapid improvement in patients' clinical status, but long-term consequences are of concern and require ongoing investigation in order to prevent limiting the otherwise important clinical achievements that have recently occurred.

Liver-Related Factors Associated with Low Vitamin D Levels in HIV and HIV/HCV Coinfected Patients and Comparison to General Population

Low 25-Hydroxyvitamin D (25[OH]D) was associated with severe fibrosis and low sustained virological response (SVR) after interferon (IFN)-based therapy in chronic hepatitis C. Furthermore, hypovitaminosis D was reported in HIV-infected individuals, but its role in liver disease progression in HIV/HCV coinfection is unknown. 25(OH)D was retrospectively measured in 237 HIV-infected patients (93 with HCV coinfection) and 76 healthy controls. Multivariate analysis included season, immuno-virological data, combined antiretroviral therapy (cART) and, in a subgroup of 51 HIV/HCV-genotype 1 coinfected patients, factors influencing SVR to pegylated-IFN and ribavirin. In a group of 20 patients, liver expression of cytochrome (CY)-P27A1 and CYP2R1, 25-hydroxylating enzymes, was assessed by immunohistochemistry. Median 25(OH)D levels were 23.4 (interquartile range 16.7-33.7) ng/mL in the HIV-infected population and 24 ng/mL (18.3-29.5) in healthy controls (p=0.9). At multiple regression analysis, only winter/spring measurements correlated with lower 25(OH)D levels. No correlation with HCV coinfection, nor with cART regimens was found. Low 25(OH)D was independently associated with advanced fibrosis in HIV/HCV coinfected patients (p=0.023), whereas no association emerged with SVR to IFN-based therapy. CYP27A1 and CYP2R1 expression was associated neither with 25(OH)D serum levels nor with HCV-infection, liver histology, or cART. In our experience, despite the high prevalence of 25(OH)D insufficiency, HIV and HCV-infection did not seem to influence vitamin D status. The role of HIV, HCV and cART on hypovitaminosis D needs further validation in larger cohorts that account for the vitamin levels in general populations and for seasonal and regional variability.

Clinical characteristics of dermatophytosis among children in a Nigerian population: role of HIV/AIDS

Background: Dermatophytosis is a common superficial mycosis. It affects virtually every child at one stage or the other, but the disease may be more frequent in individuals with immunocompromising conditions. The typical characteristic of the rash is an annular, popular rash with a healing centre and an active periphery that may have an erythematous base and it occurs in different parts of the body. Aims: To elicit the clinical characteristics of dermatophytosis among children with HIV/AIDS. Methods: Two hundred each of HIV sero-positive and sero-negative children were evaluated for dermatophytosis (and its clinical types) and the possible role of HIV was examined. Results: Thirty-two (16%) seropositive and 24(12%) sero-negative children had dermatophytosis (P = 0.086). Tinea capitis was the most prevalent among the sero-positive and was the only type seen among the sero-negative subjects. Dermatophytosis was significantly more prevalent among those with more advanced clinical stage of HIV (p = 0.000). Children in 5 – 12 year age bracket were more affected in both groups. Conclusion: Tinea capitis was the most frequent type of dermatophytosis in the study, followed by tinea corporis. Children in 5 – 12 year age bracket were more affected in both groups. Occurrence of dermatophytosis was significantly influenced by the stage of HIV disease but not by HIV status. Keywords: Characteristics dermatophytosis HIV/AIDS children in Nigeria

Chinese Human Immunodeficiency Virus-1 Patients with Different Routes of Transmission Exhibit Altered Expression Levels of Blood Dendritic Cell Subpopulations

Dendritic cells (DCs) play a pivotal role in the pathogenesis of human immunodeficiency virus-1 (HIV-1). Reduced numbers of blood DCs have been observed in individuals with chronic HIV-1 infection. In the present study, we analyzed the expression levels of monocytes, myeloid dendritic cell (mDC) precursors, mDCs, and plasmacytoid dendritic cells (pDCs), in HIV-1-infected patients in China who were infected via different routes of transmission, including heterosexual and homosexual sexual contact, and blood transmission through importation of blood or blood products, to further elucidate their role in HIV. Compared with HIV-negative individuals (n = 40), relative levels of CD11c+CD14⁻mDCs, CD11c++CD123(low) mDCs, and CD11c⁻CD123+ pDCs in total peripheral blood mononuclear cells (PBMCs) were significantly lower in all HIV patients (n = 93), and in those with blood transmission (n = 26) and heterosexual transmission (n = 43), while relative levels of CD11c+CD14⁻mDCs were significantly lower in HIV patients infected via homosexual transmission (n = 24). The results of correlation analysis demonstrated a significant negative correlation between CD4+ T-cell counts and the relative levels of CD11c++CD123(low) mDCs in HIV-I patients infected via blood transmission. There was no significant correlation between CD4+ T-cell counts and the expression level of other DC subpopulations in PBMCs from HIV patients. The results of this study suggest that HIV-1 patients with different routes of transmission exhibit altered expression levels of blood DC subpopulations, which contributes to dysregulated immune responses and pathogenesis of HIV-1.

CD40 Ligand (CD154) Incorporated into HIV Virions Induces Activation-Induced Cytidine Deaminase (AID) Expression in Human B Lymphocytes

Most AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL) arises from errors in immunoglobulin heavy-chain gene (IgH) class switch recombination (CSR) or somatic hypermutation (SHM), events that occur in germinal center (GC) B cells and require the activity of activation induced cytidine deaminase (AID). Several oncogenic viruses (EBV, HCV, HPV) can induce AID gene (AID) expression, and elevated AID expression is seen in circulating lymphocytes prior to AIDS-NHL diagnosis. Here, we report that HIV produced in peripheral blood mononuclear cells (PBMC) induced AID expression in normal human B cells. Since HIV produced in PBMC contains host cell CD40 ligand (CD40L) incorporated into the viral membrane, and CD40L is known to induce AID expression in human B cells, the role of virion-associated CD40L in HIV-induced AID expression was examined. Only viruses expressing functional CD40L were seen to induce AID expression; CD40L-negative HIV did not induce AID expression. The induction of AID expression by CD40L+ HIV was abrogated by addition of blocking anti-CD40L antibody. AID protein was detected in B cells exposed to CD40L+ HIV using intracellular multicolor flow cytometry, with most AID producing B cells expressing the CD71 activation marker on their surface. Therefore, HIV virions that express CD40L induce AID expression in B cells, and this induction appears to be due to a direct interaction between CD40L on these viruses and CD40 on B cells. These findings are consistent with a role for HIV in the direct stimulation of B cells, potentially leading to the accumulation of molecular lesions that have the potential to contribute to the development of NHL.

Innate immune natural killer cells and their role in HIV and SIV infection.

The findings that early events during HIV-1 and SIV infection of Asian rhesus macaques dictate the levels of viremia and rate of disease progression prior to the establishment of mature and effective adaptive immune responses strongly suggest an important role for innate immune mechanisms. In addition, the fact that the major target of HIV and SIV during this period of acute infection is the gastrointestinal tissue suggests that whatever role the innate immune system plays must either directly and/or indirectly focus on the GI tract. The object of this article is to provide a general overview of the innate immune system with a focus on natural killer (NK) cells and their role in the pathogenesis of lentivirus infection. The studies summarized include our current understanding of the phenotypic heterogeneity, the putative functions ascribed to the subsets, the maturation/differentiation of NK cells, the mechanisms by which their function is mediated and regulated, the studies of these NK-cell subsets, with a focus on killer cell immunoglobulin-like receptors (KIRs) in nonhuman primates and humans, and finally, how HIV and SIV infection affects these NK cells in vivo. Clearly much has yet to be learnt on how the innate immune system influences the interaction between lentiviruses and the host within the GI tract, knowledge of which is reasoned to be critical for the formulation of effective vaccines against HIV-1.

Recurrent Chromosomal Alterations in Molecularly Classified AIDS-Related Lymphomas: An Integrated Analysis of DNA Copy Number and Gene Expression

HIV-infected individuals have a significantly increased risk of developing an aggressive B-cell Non-Hodgkin Lymphoma relative to HIV(-) persons. Due to their aggressive nature, AIDS-related lymphomas (ARL) can also be more difficult to classify. Genetic abnormalities are known to play a significant role in HIV(-) lymphomagenesis. To aid in case classification and identify key pathogenetic events in ARL, we analyzed gene expression data and somatic DNA copy number changes by high-resolution array comparative genomic hybridization in tumors from 20 B-cell derived ARL (B-ARL) patients. Gene expression-based predictors robustly classified the B-ARL cases, distinguishing Burkitt lymphoma and diffuse large B-cell lymphoma, and identifying activated B-cell like and germinal center B-cell like molecular subtypes of diffuse large B-cell lymphoma. Array comparative genomic hybridization analysis revealed 13 recurrent losses and 16 recurrent gains in the B-ARL cases, including gain of 19p13.2 and loss of 16q23, not previously reported in B-ARL. The WWOX tumor suppressor gene was characterized as a candidate gene for the 16q23.1 locus and showed gene silencing or truncated transcript in 9 of 16 cases. These data demonstrate the ability to molecularly classify B-ARL lymphomas by gene expression and identified DNA copy number alterations targeted in B-ARL.

Relation between levels of infant‐, child‐ and maternal‐mortality and their rates of decline

PurposeThe purpose of this paper is to study the cross‐country relation between initial levels of infant‐, child‐ and maternal‐mortality and their rates of decline so as to see whether the so‐called Matthew effect or the inverse‐care principle operates relative to these three important health indicators.Design/methodology/approachData on the three variables for a large number of countries covering several periods between 1950 and 2007 are considered. Signs and significance of correlations between initial levels and the rates of decline over the period, and of coefficients of initial levels in regressions of rates of decline on the initial level, are studied.FindingsFirst, in a broad global context, higher initial levels of mortality are associated with significantly lower rates of decline in each of the three indicators for every period, thus providing strong support to the operation of the inverse‐care principle and the Matthew effect. Second, the high‐income countries (and transition economies) deviate from the global pattern. Third, following Hart's suggestion, the parametric contrast between the high income and the developing groups may be interpreted as indicative of stronger government intervention in the healthcare sector in high‐income countries. Fourth, the contrast may thus indicate the desirability of greater government intervention in provision of healthcare in developing countries. Fifth, operation of the inverse‐care principle and the Matthew effect is observed even in the absence of high‐HIV prevalence. Sixth, the observed negative covariation between initial mortality and its rate of decline implies cross‐country divergence in these core indicators of health.Originality/valueFirst, this is the only study to investigate the operation of the inverse‐care principle relative to infant mortality for such a large number of countries and such a long period. Second, it is also the only study to extend the investigation to child‐mortality and maternal‐mortality, which are heavily emphasized in the millennium development goals. Third, the patterns are studied not only merely for the entire set of countries, but also for several subgroups. Fourth, the observed parametric contrasts are interpreted as possibly reflecting the importance of government intervention in the healthcare sector in mitigating the operation of the inverse‐care phenomenon. Fifth, an effort is made to factor out the role of HIV so as to show that the pattern is not significantly altered by high prevalence of HIV in poor countries. Sixth, the implied cross‐country divergence in these important health variables is suggestive of the need for caution in interpreting the conclusions stated by some scholars about convergence in several quality‐of‐life indicators. Last, contrary to what some scholars have suggested, not merely does it not seem to be the case that the inverse‐care proposition relative to infant mortality is observed only in exceptional cases, but the reported evidence suggests that the proposition holds globally over long periods even for child‐ and maternal‐mortality.

New cholesterol-specific antibodies remodel HIV-1 target cells’ surface and inhibit their in vitro virus production

The importance of membrane rafts in HIV-1 infection is still in the focus of interest. Here, we report that new monoclonal anticholesterol IgG antibodies (ACHAs), recognizing clustered membrane cholesterol (e.g., in lipid rafts), rearrange the lateral molecular organization of HIV-1 receptors and coreceptors in the plasma membrane of HIV-1 permissive human T-cells and macrophages. This remodeling is accompanied with a substantial inhibition of their infection and HIV-1 production in vitro. ACHAs promote the association of CXCR4 with both CD4 and lipid rafts, consistent with the decreased lateral mobility of CXCR4, while Fab fragments of ACHAs do not show these effects. ACHAs do not directly mask the extracellular domains of either CD4 or CXCR4 nor do they affect CXCR4 internalization. No significant inhibition of HIV production is seen when the virus is preincubated with the antibodies prior to infection. Thus, we propose that the observed inhibition is mainly due to the membrane remodeling induced by cholesterol-specific antibodies on the target cells. This, in turn, may prevent the proper spatio-temporal juxtaposition of HIV-1 glycoproteins with CD4 and chemokine receptors, thus negatively interfering with virus attachment/entry.

Possible role of HIV in stroke: HIV status of stroke patients as seen in A Tertiary Hospital

Possible role of HIV in stroke: HIV status of stroke patients as seen in A Tertiary Hospital