Background.

 Previous studies identified specific Chlamydia trachomatis strains circulating among men who have sex with men (MSM). This study investigates whether distinct C. trachomatis strains circulate among subpopulations within the MSM community.Methods. Participants were recruited at the sexually transmitted infections (STI) clinic of the Public Health Service of Amsterdam, from 2008 to 2009. C. trachomatis samples were typed using multilocus sequence typing (MLST). Epidemiological and clinical data were derived from questionnaires and patient records.

Results.

 Typing of 277 samples from 260 MSM identified distinct C. trachomatis strains, circulating concurrently over time. Men infected with lymphogranuloma venereum (LGV) inducing strains were more likely to be HIV-infected, more often had a history of STIs, and displayed higher sexual risk behavior. No such associations were found for non-LGV-inducing strains. MSM infected with heterosexual-associated strains were often younger (p=0·04) and more often reported sex with women (p=0·03), compared with men infected with MSM-associated strains.

Conclusions.

 With the exception of LGV-inducing strains, no evidence was found that different C. trachomatis strains circulated in distinct subpopulations of MSM. This indicates that no separate transmission networks for C. trachomatis among MSM existed. However, younger MSM and bisexuals were more often infected with heterosexual-associated C. trachomatis strains.

BACKGROUND:

The prevalence of myocarditis and cardiotropic viral infection in human immunodeficiency virus (HIV)-associated cardiomyopathy is unknown in Africa.

METHODS:

Between April 2002 and December 2007, we compared the prevalence of myocarditis and cardiotropic viral genomes in HIV-associated cardiomyopathy cases with HIV-negative idiopathic dilated cardiomyopathy patients (i.e. negative controls for immunodeficiency) and heart transplant recipients (i.e. positive controls for immunodeficiency) who were seen at Groote Schuur Hospital, Cape Town, South Africa. Myocarditis was sought on endomyocardial biopsy using the imunohistological criteria of the World Heart Federation in 33 patients, 14 of whom had HIV-associated cardiomyopathy, eight with idiopathic dilated cardiomyopathy and 11 heart transplant recipients.

RESULTS:

Myocarditis was present in 44% of HIV-associated cardiomyopathy cases, 36% of heart transplant recipients, and 25% of participants with idiopathic dilated cardiomyopathy. While myocarditis was acute in 50% of HIV- and heart transplant-associated myocarditis, it was chronic in all those with idiopathic dilated cardiomyopathy. Cardiotropic viral infection was present in all HIV-associated cardiomyopathy and idiopathic dilated cardiomyopathy cases, and in 90% of heart transplant recipients. Multiple viruses were identified in the majority of cases, with HIV-associated cardiomyopathy, heart transplant recipients and idiopathic dilated cardiomyopathy patients having an average of 2.5, 2.2 and 1.1 viruses per individual, respectively.

CONCLUSIONS:

Acute myocarditis was present in 21% of cases of HIV-associated cardiomyopathy, compared to none of those with idiopathic dilated cardiomyopathy. Infection with multiple cardiotropic viruses may be ubiquitous in Africans, with a greater burden of infection in acquired immunodeficiency states.

OBJECTIVE::

Although passive immunization with anti-HIV-1 Env IgG1 neutralizing monoclonal antibodies (nmAbs) prevented simian-human immunodeficiency virus (SHIV) infection in rhesus monkeys, IgA nmAbs have not been tested. Here, we sought to determine whether human anti-HIV-1 dimeric (d)IgA1, dIgA2, and IgG1 differ in their ability to prevent mucosal R5 SHIV acquisition in rhesus monkeys.

DESIGN:

: DIgA1, dIgA2, and IgG1 versions of nmAb HGN194 were applied intrarectally in three rhesus monkey groups 30 min before intrarectal SHIV challenge.

METHODS::

After a control pharmacokinetic study confirmed that nmAb concentrations in rectal fluids over time were similar for all HGN194 isotypes, control and nmAb-treated animals were challenged intrarectally with an R5 SHIV, and viral loads were monitored.

RESULTS::

Unexpectedly, dIgA1 provided the best protection in vivo - although all nmAbs showed similar neutralizing activity in vitro. Five out of the six dIgA1-treated rhesus monkeys remained virus-free compared to only one out of six animals given dIgA2 (P = 0.045 by log-rank test) and two out of six rhesus monkeys treated with IgG1 forms of the nmAb (P = 0.12). Protection correlated significantly with virion capture activity by a given nmAb form, as well as inhibition of transcytosis of cell-free virus across an epithelial cell layer in vitro.

CONCLUSIONS::

Our data imply that dIgA1-mediated capturing of virions in mucosal secretions and inhibition of transcytosis can provide significant prevention of lentiviral acquisition - over and above direct virus neutralization. Vaccine strategies that induce mucosal IgA, especially IgA1, should be developed as a first line of defense against HIV-1, a virus predominantly transmitted mucosally.

Human herpes virus-8 (HHV-8) is etiologically associated with Kaposi's sarcoma. There is insufficient information on the epidemiology of HHV-8 infection from India. Blood samples from 87 human immunodeficiency virus (HIV)-infected individuals and 84 normal healthy blood donors were tested for the HHV-8 IgG antibodies. Further, a total of 309 whole blood samples from treatment-naïve HIV-1-infected individuals and from 70 normal healthy individuals were also collected and tested for HHV-8 DNA. The seroprevalence of HHV-8 was 4.7% in the South Indian population. There was no significant difference in the seroprevalence of HHV-8 in the HIV-infected and uninfected patients. None of the 379 samples tested were positive for HHV-8 DNA. Our study revealed a very low exposure of the South Indian patient population to HHV-8 and multicentric epidemiological studies are needed to understand the prevalence of HHV-8 in different regions of India and to confirm any gender-specific differences in seroprevalence.

PURPOSE:

Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor, widely prescribed for type 1 human immunodeficiency virus infection. A small proportion of individuals treated with NVP experience severe cutaneous adverse events, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Our aim was to verify whether genetic variability in NVP-metabolizing cytochromes or in transporter genes could be involved in susceptibility to SJS/TEN.

METHODS:

Twenty-seven patients with NVP-induced SJS/TEN and 78 controls, all from Mozambique, were genotyped for the ABCB1 and ABCC10 transporter genes and for CYP2B6, CYP3A4 and CYP3A5 cytochrome gene variants. A case-control and a genotype-phenotype analysis were performed.

RESULTS:

CYP2B6 G516T and T983C single nucleotide polymorphisms (SNPs) were found to be associated with SJS/TEN susceptibility. The 983C allele in particular was found to be highly associated with a higher risk to develop SJS/TEN [odds ratio (OR) 4.2, P = 0.0047]. The GT haplotype (wildtype for both SNPs) showed a protective effect, with an OR = 0.33 (P = 0.0016).

CONCLUSIONS:

This is the first study showing that genetic variability in a metabolizing enzyme can also contribute to NVP-induced SJS/TEN susceptibility.

Background:

Psoriasis is a chronic skin disorder. The most frequently used systemic anti-psoriatic therapy in Germany is fumaric acid esters (FAE).

Objectives:

We aimed to characterize immunological changes in psoriasis patients under FAE treatment. Methods and Materials: Over 200 flow-cytometry analyses of blood from 27 psoriasis patients and histological, molecular, and serological analyses of samples from a patient who developed Kaposi sarcoma (KS) during FAE therapy were performed.

Results:

The patients receiving FAE showed decreased CD8+ T cell counts, in particular during the first six months. The CD4+ T cell decline was less pronounced and delayed in time. In a patient with KS, we found a profound CD4 and CD8 lymphocytopenia, as well as a NK cell number reduction, although leukocyte and lymphocyte counts were within the recommended limits. The patient was HIV negative, but positive for HHV8. After cessation of FAE therapy, KS regressed. Discussion: HHV8 infection and iatrogenic T cell reduction, prominently of CD8+ T cells, could have contributed to KS development in this patient. Therefore, we suggest a control of CD4+ and CD8+ T cell counts in addition to the commonly-used differential blood counts in patients with a higher HHV8 prevalence or at high risk of other latent viral infections.

We describe our experience with stent-graft placement in a patient with a clinically diagnosed syphilitic aortic aneurysm.The patient was a 43-year-old man with syphilitic and human immunodeficiency virus (HIV) co-infection. Computed tomography (CT) revealed an aortic aneurysm with 89 mm in maximum size which was located at distal aortic arch and was considered syphilis derived saccular aneurysm. The aneurysm was judged at high risk of rupture from its shape. We decided to perform stent-graft implantation. Before surgery, the patient was given antibacterial and anti-HIV agents. Hand-made fenestrated stent graft by Tokyo Medical University was implanted. The graft was placed from the ascending aorta to Th 9 level in the descending aorta. The aneurysm completely disappeared during follow-up, with no flare-up of syphilitic infection up to 2 years after surgery.The number of patients with syphilis and human immunodeficiency virus co-infection is now increasing. Stent-graft implantation may be an effective treatment in such immunocompromised patients.

Tumor necrosis factor receptor-associated factor (TRAF) signaling plays a central role in many biological activities, such as the regulation of immune and inflammatory responses and control of apoptosis, which are key events in the pathogenesis of the human immunodeficiency virus (HIV)-1 and the hepatitis C virus (HCV) infections. Here we show that TRAF2, TRAF5 and TRAF6 interact with the HIV-1 Nef protein, an immunomodulatory viral protein expressed and released by cells infected by the virus. We also found that TRAF2 and TRAF5 interact with the HCV Core protein. Interestingly, we observed that HIV-1 Nef interacts with HCV Core. The activation of TRAF (2, 5, 6) - mediated by HIV-1 Nef and HCV Core - enhanced the activation of the nuclear factor-kappa B (NF-κB) and increased HIV-1 replication in monocyte- derived macrophages (MDMs). The knockdown of TRAF2, TRAF5 and TRAF6 resulted in decreased NF-κB activation and reduced HIV-1 replication in MDMs. Our results reveal a mechanism by which the activation of the TRAF pathway by HIV-1 Nef and HCV Core favors the replication of HIV-1 in macrophages and could be a critical factor for optimal replication of HIV-1 in macrophages of HIV-HCV-coinfected patients.

Management of co-infection with malaria and HIV is a major challenge to public health in developing countries and yet potential drug-drug interactions between antimalarial and antiviral regimens have not been adequately investigated in people with both infections. Each of the constituent components of artemether-lumefantrine, the first-line regimen for malaria treatment in Nigeria, and nevirapine, a major component of highly active antiretroviral therapy, are drugs metabolised by the cytochrome P450 3A4 isoenzyme system, which is also known to be induced by nevirapine. We examined potential interactions between lumefantrine and nevirapine in 68 HIV-positive adults, all of whom were diagnosed with asymptomatic Plasmodium falciparum infections by microscopy. Post hoc PCR analysis confirmed the presence of P. falciparum in only a minority of participants. Day 7 capillary blood levels of lumefantrine were significantly higher in HIV positive participants than in 99 HIV negative controls (P=0.0011). Associations between day 7 levels of lumefantrine and risk of persistent parasitaemia could not be evaluated due to inadequate power. Further investigations of the impact of nevirapine on in vivo malaria treatment outcomes in HIV-infected patients are thus needed.

BACKGROUND:

To achieve the goal of United Nations of elimination of new HIV infections, a program of prevention of mother-to-child transmission (PMTCT) was launched in Guangdong province. The objective of this study is to evaluate the effectiveness of the PMTCT program.

METHODS:

The retrospective cross-section analysis was conducted using the data of case reported cards of HIV positive mothers and their infants from 2007 to 2010 in Guangdong province, and 108 pairs of eligible subjects were obtained. We described the data and compared the rates of MTCT by various PMTCT interventions respectively.

RESULTS:

The overall rate of HIV MTCT was 13.89% (15) among 108 pairs of HIV positive mothers and their infants; 60.19% (65) of the mothers ever received ARVs, 80.56% (87) of infants born to HIV positive mothers ever received ARVs, but 16.67% (18) of the mothers and infants neither received ARVs. Among all the mothers and infants, who both received ARVs, received triple ARVs, mother received ARVs during pregnancy, and both received ARVs and formula feeding showed the lower rates of HIV MTCT, and the rates were 8.06%, 2.50%, 5.77%, and 6.67% respectively. In infants born to HIV positive mother, who received mixed feeding had a higher HIV MTCT up to 60.00%. Delivery mode might not relative to HIV MTCT.

CONCLUSIONS:

The interventions of PMTCT program in Guangdong could effectively reduce the rate of HIV MTCT, but the effectiveness of the PMTCT program were heavily cut down by the lower availability of the PMTCT interventions.