No therapies have been proven to persistently improve the outcome of HTLV-I-associated myelopathy. Clinical benefit has been reported with zidovudine and with lamivudine in observational studies. We therefore conducted a randomised, double blind, placebo controlled study of six months combination therapy with these nucleoside analogues in sixteen patients. Primary outcomes were change in HTLV-I proviral load in PBMCs and clinical measures. Secondary endpoints were changes in T-cell subsets and markers of activation and proliferation. Six patients discontinued zidovudine. No significant changes in pain, bladder function, disability score, gait, proviral load or markers of T-cell activation or proliferation were seen between the two arms. Active therapy was associated with an unexplained decrease in CD8 and non-T lymphocyte counts. Failure to detect clinical improvement may have been due irreversible nerve damage in these patients with a long clinical history and future studies should target patients presenting earlier. The lack of virological effect but may reflect a lack of activity of these nucleoside analogues against HTLV-I RT in vivo, inadequate intracellular concentrations of the active moiety or the contribution of new cell infection to maintaining proviral load at this stage of infection may be relatively small masking the effects of RT inhibition.

Background: We used a PCR-based approach to study the prevalence of genetic sequences related to a gammaretrovirus, xenotropic murine leukemia virus-related virus, XMRV, in human prostate cancer. This virus has been identified in the US in prostate cancer patients and in those with chronic fatigue syndrome. However, with the exception of two patients in Germany, XMRV has not been identified in prostate cancer tissue in Europe. Most putative associations of new or old human retroviruses with diseases have turned out to be due to contamination. We have looked for XMRV sequences in DNA extracted from formalin-fixed paraffin- embedded prostate tissues. To control for contamination, PCR assays to detect either mouse mitochondrial DNA (mtDNA) or intracisternal A particle (IAP) long terminal repeat DNA were run on all samples, owing to their very high copy number in mouse cells. Results: In general agreement with the US prevalence, XMRV-like sequences were found in 4.8% of prostate cancers. However, these were also positive, as were 21.5% of XMRV-negative cases, for IAP sequences, and many, but not all were positive for mtDNA sequences. Conclusions: These results show that contamination with mouse DNA is widespread and detectable by the highly sensitive IAP assay, but not always with less sensitive assays, such as murine mtDNA PCR. This study highlights the ubiquitous presence of mouse DNA in laboratory specimens and offers a means of rigorous validation for future studies of murine retroviruses in human disease.

Given that we still do not have an effective vaccine against HIV, the development of novel biomedical methods for preventing HIV transmission remains a top priority in controlling the HIV pandemic.

This review considers the use of antiretroviral drugs specifically to prevent HIV transmission. Antiretroviral therapy (ART) can be implemented for the protection of uninfected individuals both before (preexposure prophylaxis) and after (postexposure prophylaxis) exposure to HIV infection. Preexposure prophylaxis may be used coitally dependently when individuals are intermittently exposed or by continuous daily dosing for those constantly exposed; postexposure prophylaxis is used in 28-day courses. Alternatively, ART can be used strategically to reduce the viral load and consequent infectiousness of an HIV-infected individual, thereby limiting the risk of onward viral transmission. A policy of universal HIV testing to enhance the identification of all HIV-positive individuals followed by immediate treatment of all HIV-positive individuals, irrespective of their CD4 cell counts (universal test and treat), has been postulated as a potential tool capable of reducing HIV incidence at a population level. This concept represents a paradigm shift in the use of ART, targeting infectious individuals for prevention rather than protecting uninfected exposed populations. This strategy could have the advantage of preventing transmission and reducing HIV incidence at a population level, as well as delivering universal access to therapy for all people living with HIV and AIDS, potentially eliminating mother-to-child HIV transmission and limiting concomitant diseases such as tuberculosis. This review critically examines the scientific basis of ART for HIV prevention, summarizing the risks and opportunities of the potential expansion of ART for prevention. Specifically, we consider the evidences for and against targeting HIV-uninfected individuals compared with enhanced HIV testing and treatment of HIV-infected individuals in terms of impact on viral transmission.

To describe the frequency and risk factors of non-B HIV-1 subtypes in men who have sex with men (MSM) in the UK. Observational study. MSM diagnosed with HIV-1 infection from 1980-2007, with HIV genotype held in the UK HIV Drug Resistance Database were identified. Protease and reverse transcriptase sequences were collected and viral clade determined using the REGA algorithm. Associations between demographic variables and subtype were analysed using logistic regression. The prevalence of non-B HIV-1 infection amongst MSM in the UK was 5.4% (437/8058). In the UK this increased with year of diagnosis from pre1996 to 2002, and has subsequently remained relatively stable at around 7-9% after 2002, with a recent increase in 2007 to 13%. Multivariate analysis showed that acquisition of non-B HIV-1 infection was independently associated with later year of HIV diagnosis (P < 0.001), black ethnicity (P < 0.001) and non-European country of birth (P = 0.01). Age was also associated with subtype with individuals aged 25-39 years being less likely to have non-B virus than those aged less than 25 years (P = 0.01). Restricting the analysis to white men born in the UK, the association between subtype and year of diagnosis remained statistically significant (P < 0.001), as did the association with age (P < 0.001). The number of MSM in the UK infected with non-B clade HIV-1 is increasing, suggesting that the sociodemographic boundaries between HIV-1 viral subtypes globally are diminishing. Should viral subtypes be relevant to clinical disease progression or vaccine design, the changing pattern of distribution will need to be taken into account.