"I will start treatment when I think the time is right":HIV-positive gay men talk about their decision not to access antiretroviral therapy.

In a qualitative study, 20 HIV-infected Australian gay men were interviewed about their decision not to access antiretroviral drug therapy. The main reasons given for the decision were fear of side effects; fear of long-term damage to body organs; the inconvenience of the treatment regimens; belief that the regimen's demands would be a threat to morale; and belief that there was no reason to start therapy in the absence of AIDS-related symptoms. Actions taken by the men to monitor and maintain their health included seeing a doctor regularly; having regular T-cell and viral load tests; and trying to maintain a positive outlook by not letting HIV/AIDS 'take over' their lives. Almost half the men considered they had been subjected to unreasonable pressure to access therapy and there was considerable pride at having resisted this pressure. The findings suggest that the men disagreed with the biomedical model for managing HIV/AIDS only on the question of if and when to access therapy. They also suggest that underlying the men's dissent from the biomedical model was a different mode of thinking than is required by the model: while the model demands thinking that is abstract, the men focused strongly on factors close to the 'here and now' of immediate experience. The practical implications of the findings are explored.

Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy

Objective: To assess the evidence for the effectiveness of increasing numbers of drugs in antiretroviral combination therapy.

Design: Systematic review, meta-analysis, and meta-regression of fully reported randomised controlled trials. All studies included compared quadruple versus triple therapy, triple versus double therapy, double versus monotherapy, or monotherapy versus placebo or no treatment.

Participants: Patients with any stage of HIV infection who had not received antiretroviral therapy.

Main outcome measures: Changes in disease progression or death (clinical outcomes); CD4 count and plasma viral load (surrogate markers).
Search strategy: Six electronic databases, including Medline, Embase, and the Cochrane Library, searched up to February 2001.

Results: 54 randomised controlled trials, most of good quality, with 66 comparison groups were included in the analysis. For both the clinical outcomes and surrogate markers, combinations with up to and including three (triple therapy) were progressively and significantly more effective. The odds ratio for disease progression or death for triple therapy compared with double therapy was 0.6 (95% confidence interval 0.5 to 0.8). Heterogeneity in effect sizes was present in many outcomes but was largely related to the drugs used and trial quality.

Conclusions: Evidence from randomised controlled trials supports the use of triple therapy. Research is needed on the effectiveness of quadruple therapies and the relative effectiveness of specific combinations of drugs.

Hepatitis B Virus transmission and hepatocarcinogenesis: a 9 year retropective cohort of 13676 relatives with hepatocellular carcinoma

Background/Aims
Familial clustering of hepatitis B virus (HBV) infection is related to perinatal transmission, and is the main cause of familial-type hepatocellular carcinoma (HCC). The route of HBV transmission differs between the children and siblings of patients with HCC. This study examined the differences in HBV carrier rates and HCC-related mortality between two generations in HCC families.
Methods
From 1992 to 1997, relatives of individuals with HCC were screened prospectively with ultrasonography, alpha-fetoprotein, liver biochemistry tests and viral markers. Total HCC-related deaths during a 9-year period were compared between the generations of index patients and their children.
Results
The study included a total of 13 676 relatives in two generations. More HCC-related deaths occurred in the index patient generation than in the child generation. Furthermore, children of female index patients had higher rates of liver cancer related mortality than children of male index patients. The same was true when the analysis was limited to male HBV carriers. The prevalence of HBsAg in the offspring of HBsAg positive mothers was 66% in the child generation and 72% in the index patient generation. These high prevalences indicated high maternal HBV replication status.
Conclusions
Perinatal transmission and maternal viral load are important risk factors in hepatocarcinogenesis.

Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1

Manifestations of viral infections can differ between women and men, and marked sex differences have been described in the course of HIV-1 disease. HIV-1-infected women tend to have lower viral loads early in HIV-1 infection but progress faster to AIDS for a given viral load than men. Here we show substantial sex differences in the response of plasmacytoid dendritic cells (pDCs) to HIV-1. pDCs derived from women produce markedly more interferon-alpha (IFN-alpha) in response to HIV-1-encoded Toll-like receptor 7 (TLR7) ligands than pDCs derived from men, resulting in stronger secondary activation of CD8(+) T cells. In line with these in vitro studies, treatment-naive women chronically infected with HIV-1 had considerably higher levels of CD8(+) T cell activation than men after adjusting for viral load. These data show that sex differences in TLR-mediated activation of pDCs may account for higher immune activation in women compared to men at a given HIV-1 viral load and provide a mechanism by which the same level of viral replication might result in faster HIV-1 disease progression in women compared to men. Modulation of the TLR7 pathway in pDCs may therefore represent a new approach to reduce HIV-1-associated pathology.

Prevalence of beak and feather disease virus in wild Platycercus elegans: comparison of three tissue types using a probe-based real-time qPCR test

The detection of avian viruses in wild populations has considerable conservation implications. For DNA-based studies, feathers may be a convenient sample type for virus screening and are, therefore, an increasingly common technique. This is despite recent concerns about DNA quality, ethics, and a paucity of data comparing the reliability and sensitivity of feather sampling to other common sample types such as blood. Alternatively, skeletal muscle tissue may offer a convenient sample to collect from dead birds, which may reveal viraemia. Here, we describe a probe-based quantitative real-time PCR for the relative quantification of beak and feather disease virus (BFDV), a pathogen of serious conservation concern for parrots globally. We used this method to test for BFDV in wild crimson rosellas (Platycercus elegans), and compared three different sample types. We detected BFDV in samples from 29 out of 84 individuals (34.5%). However, feather samples provided discordant results concerning virus presence when compared with muscle tissue and blood, and estimates of viral load varied somewhat between different sample types. This study provides evidence for widespread infection of BFDV in wild crimson rosellas, but highlights the importance of sample type when generating and interpreting qualitative and quantitative avian virus data.

Defining the interaction of HIV-1 with the mucosal barriers of the female reproductive tract

Worldwide, HIV-1 infects millions of people annually, the majority of whom are women. To establish infection in the female reproductive tract (FRT), HIV-1 in male ejaculate must overcome numerous innate and adaptive immune factors, traverse the genital epithelium, and establish infection in underlying CD4(+) target cells. How the virus achieves this remains poorly defined. By utilizing a new technique, we define how HIV-1 interacts with different tissues of the FRT using human cervical explants and in vivo exposure in the rhesus macaque vaginal transmission model. Despite previous claims of the squamous epithelium being an efficient barrier to virus entry, we reveal that HIV-1 can penetrate both intact columnar and squamous epithelial barriers to depths where the virus can encounter potential target cells. In the squamous epithelium, we identify virus entry occurring through diffusive percolation, penetrating areas where cell junctions are absent. In the columnar epithelium, we illustrate that virus does not transverse barriers as well as previously thought due to mucus impediment. We also show a statistically significant correlation between the viral load of inocula and the ability of HIV-1 to pervade the squamous barrier. Overall, our results suggest a diffusive percolation mechanism for the initial events of HIV-1 entry. With these data, we also mathematically extrapolate the number of HIV-1 particles that penetrate the mucosa per coital act, providing a biological description of the mechanism for HIV-1 transmission during the acute and chronic stages of infection.