Current HIV Research - Volume 11, Issue 8, 2013

HIV infection is characterized by aberrant B cell responses and B cell dysfunction. These dysfunctional responses have been extensively documented in peripheral blood and organized lymphoid tissues such as the lymph nodes. Though the loss of CD4 T cell help has been thought to play a key role in dysfunctional B cell responses, recent studies have implicated a subset of CD4 T helper cells called the T follicular helper (Tfh) cells in this process. Tfh cells interact with B cells and play a key role in mediating the germinal center reaction, and driving the differentiation and maturation of B cells. Why Tfh expands in some HIV infected individuals as compared to their loss in others is still not clear. Here we review some of the recent developments in the field and discuss the implications of Tfh cell dysregulation on B cell responses during HIV infection.

Acquired Immunodeficiency Syndrome (AIDS) was discovered 30 years ago and was followed by the identification and characterization of its causative agent, Human Immunodeficiency Virus (HIV). Increasing spread of retroviral infections has impelled science to understand the evolution of retroviruses from primates to humans. In the course of evolution, host cells have developed intracellular proteins to counteract the transforming viral defence system. Such inhibitory endogenous intracellular proteins are known as restriction factors. Tripartite motif protein isoform 5 alpha (TRIM5α), Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC), and Tetherin proteins are few important restriction factors that have been extensively studied. Several evidences have conveyed information regarding specific adaptations occurring in HIV-1 and its relatives to inhibit these host defenses; making the study more interesting. The characteristic potential of restriction factors to restrict the replication of retroviruses was enticing when studies were found that HIV-1 virus cannot infect nonhuman primate species. This review emphasizes on TRIM5α as a restriction factor and its significance in the evolution of retroviruses. It also accentuates the role of polymorphism within the regions of TRIM5α in both human and primate species that eventually affect the cross-species transmission of immunodeficiency viruses.

Antigen-presenting viral vectors have been extensively used as vehicles for the presentation of antigens to the immune system in numerous vaccine strategies. Particularly in HIV vaccine development efforts, two main viral vectors have been used as antigen carriers: (a) live attenuated vectors and (b) virus-like particles (VLPs); the former, although highly effective in animal studies, cannot be clinically tested in humans due to safety concerns and the latter have failed to induce broadly neutralizing anti-HIV antibodies. For more than two decades, Inoviruses (non-lytic bacterial phages) have also been utilized as antigen carriers in several vaccine studies. Inoviral vectors are important antigen-carriers in vaccine development due to their ability to present an antigen on their outer architecture in many copies and to their natural high immunogenicity. Numerous fundamental studies have been conducted, which have established the unique properties of antigen-displayed inoviral vectors in HIV vaccine efforts. The recent isolation of new, potent anti-HIV broadly neutralizing monoclonal antibodies provides a new momentum in this emerging technology.

To export intron-containing viral mRNAs that encode the structural components of new viral particles from the nucleus to the cytoplasm, HIV-1 uses the cellular CRM1 export pathway that is exploited by the viral Rev protein. Rev multimerizes on the Rev response element (RRE) present in the intron-containing RNA species to bridge these to the cellular export factor CRM1. As a result, this Rev-RRE complex is exported to the cytoplasm. This review provides a systematic overview of different aspects of the crucial function of Rev multimerization, such as co-operative Rev-Rev and Rev-RNA interactions, the biological function of Rev multimerization, the relevance of Rev multimerization in the absence of RRE and its potential as a therapeutic target.

Enteroaggregative Escherichia coli (EAEC) have been isolated from both HIV-positive and non-HIV diarrheal samples. In this study a collection of 18 isolates from these two groups were compared for biofilm formation and antibiotic resistance and for the presence of 14 virulence-related genes. All the HIV-positive and over 66% of the non- HIV strains were PCR-negative for adhesion-related sequences indicating that as yet unknown adhesins may play a role. However, despite some variations, the prevalence rate of the virulence-related genes was not significantly different in the two groups. HIV-positive isolates were biofilm producer but only a single weak biofilm former was observed among the non-HIV strains. The rate of resistance to most of the antibiotics used was higher among the HIV-positive group than the non-HIV isolates, but was significantly higher for amoxicillin-calvulanic acid (100%) and nalidixic acid (55.5%). Pulse field gel electrophoresis of the isolates produced 17 unique profiles reflecting the exiting heterogeneity of the isolates.

Objectives: The aim of the study was to identify variables that can influence atazanavir plasma concentration. Methods: We retrospectively analysed atazanavir trough concentration of HIV infected patients who performed therapeutic drug monitoring between October 2007 and July 2011. Qualitative variables were compared with X2 test while continuous ones with Mann-Whitney and Student’s t-test. A linear regression model was used to investigate factors influencing atazanavir plasma concentration. Therefore, we analysed the impact of cirrhosis on atazanavir pharmacokinetic variability. Results: 255 plasma samples from 179 patients were analysed. At the univariate analysis female gender (+144.4 ng/mL; p=0.05) and tenofovir (+196.8 ng/mL; p=0.002) were associated with higher atazanavir concentrations. The multivariate model confirmed these two variables (+164.6 ng/mL; p=0.02 and +150.4 ng/mL; p=0.01) as independently associated with higher atazanavir trough concentration. The analysis of cirrhotic population showed an influence of tenofovir (-255.9 ng/mL; p=0.01), increased AST (+95.3 ng/mL; p=0.09), ALT (+67.9 ng/mL; p=0.07) and creatinine (+517.2 ng/mL; p=0.04). The multivariate model confirm that tenofovir was associated with lower atazanavir trough concentration (-284.1 ng/mL; p=0.005) while AST values significantly increased atazanavir concentrations (+114.5 ng/mL; p=0.03). Discussion: Atazanavir is a safe and manageable drug. Our results suggest that female patients tend to have higher atazanavir plasma concentration, while the effect of tenofovir needs to be better clarified.

Cryptococcus neoformans is an important cause of morbidity in HIV-infected patients worldwide. In the northern region of Brazil, the prevalence of this infection is poorly known due to a lack of systematic investigations. This study aimed to determine the occurrence of cryptococcosis by detecting antigenaemia in HIV-infected patients in the State of Pará, Brazil. A latex Cryptococcus antigen detection kit was used to test 418 serum samples from HIV-infected patients seen at two Infectious Disease Specialized Units in the State of Pará. The C. neoformans antigenaemia prevalence was 2.6%, and titres reached 1:8. The cases occurred mainly in asymptomatic females, and 45% presented CD4+ T lymphocyte counts of fewer than 200 cells/mm3. These results show the importance of early C. neoformans antigenaemia detection to prevent fungal disease.

This is a retrospective study based on surveillance of Human Immunodeficiency Virus type-1 (HIV-1) positive pregnant women and their children in China’s Zhejiang Province. HIV counseling and testing, mother and infant characteristics, and outcomes are reported here. This study compares two principal periods, the period from 2007-2009 and the period from 2010 to 2013. The average rate of HIV counseling among pregnant women rose from 84.87% during the earlier period to 99.08% during the latter period. And the rate of HIV testing also rose significantly, from 80.60% to 98.58%. The HIV-1 prevalence among pregnant women increased slightly, from 0.01% to 0.02%. Over 70% of infected women were migrants. Half of these HIV-1 positive pregnant women were 20-30 years old. Significant differences in the characteristics of HIV-1 positive pregnant women were observed with time. The proportion of women who were employed increased dramatically from an average of 15.03% during 2007-2009 to an average of 31.34% during 2010-2013 and the proportion of women who had completed high school education increased from 0.52% to 6.51%. During 2007-2009, an average of 3.11% of these women was diagnosed before their pregnancies. During 2010-2013, this average reached to 32.53%. Sexual contact remained the primary route of transmission route during both periods, accounting for half of the infections. The proportion of women who had acquired HIV by blood transfusion declined noticeably. The proportion of mothers and children with antiretroviral therapy increased considerably over time. The overall mother-to-child transmission rate was found to be 7.14%. Although some progress has been made, further work should be performed, fostering early identification and timely therapy. Particular attention should be paid to health care of migrants.