Partners of people on ART - a New Evaluation of the Risks (The PARTNER study): design and methods.

BACKGROUND: It is known that being on antiretroviral therapy reduces the risk of HIV transmission through sex. However it remains unknown what the absolute level of risk of transmission is in a person on ART with most recent measured HIV plasma viral load<50 c/mL in the absence of condom use. There are no data on risk of transmission for anal sex in MSM when the index partner is on ART. METHODS/DESIGN: The PARTNER study is an international, observational multi-centre study, taking place from 2010 to 2014 in which HIV serodifferent partnerships who at enrolment reported recently having had condom-less vaginal or anal sexual intercourse are followed over time, with 46 monthly reporting of transmission risk behaviour through a confidential self completed risk behaviour questionnaire and with 46 monthly HIV testing for the HIV negative partner. The objective is to study (i) the risk of HIV transmission to partners, in particular in partnerships that continue not to use condoms consistently and the HIV-positive partner is on therapy with a viral load<50 copies/mL and (ii) why some partnerships do not use condoms, to describe the proportion who begin to adopt consistent condom use, and factors associated with this. For any negative partner who becomes infected phylogenetic analysis will be used following anonymisation of the samples to assess if transmission had been from the HIV infected partner. DISCUSSION: This observational study will provide missing information on the absolute risk of HIV transmission for both vaginal and anal sex when the index case is on ART with a VL<50 copies/mL in the absence of condom use.

Treatment of heavily antiretroviral-experienced HIV-infected patients.

In 2008, the goal of antiretroviral therapy is the suppression of viral load to undetectable levels (<50 HIV-RNA copies/ml) even in heavily pretreated patients harboring multidrug-resistant viruses. This ambitious goal can be achieved by combining at least two fully active antiretroviral drugs with an optimized background regimen according to genotypic and phenotypic resistance testing. This favorable situation has been accomplished by the advent of new compounds in already known drug classes (e.g. second-generation protease inhibitors and nonnucleoside reverse transcriptase inhibitors) as well as thanks to the development of new drug classes with a different mode of action (e.g. fusion inhibitors, integrase inhibitors, and coreceptor antagonists). Moreover, new diagnostic tools have been developed to better predict virologic response and tolerability of a given regimen in the individual patient, such as weighted mutation scores, virtual phenotypes, viral tropism assays, pharmacogenetics and pharmacokinetic analyses. This new array of therapeutic and diagnostic tools requires a highly specialized training of the treating physician to achieve the ultimate goal of halting disease progression. The purpose of this review is to introduce the new drugs and drug classes, and discuss their safety and use in combination therapy of multidrug-resistant viruses, guided by new diagnostic tools.

Transfer of Autologous Gene-modified T Cells in HIV-infected Patients with Advanced Immunodeficiency and Drug-resistant Virus.

Drug toxicity and viral resistance limit the long-term efficacy of antiviral drug treatment for human immunodeficiency virus (HIV) infection. Thus, alternative therapies need to be explored. We tested the infusion of T lymphocytes transduced with a retroviral vector (M87o) that expresses an HIV entry-inhibitory peptide (maC46). Gene-modified autologous T cells were infused into ten HIV-infected patients with advanced disease and multidrug-resistant virus during anti-retroviral combination therapy. T-cell infusions were tolerated well, with no severe side effects. A significant increase of CD4 counts was observed after infusion. At the end of the 1-year follow-up, the CD4 counts of all patients were still around or above baseline. Gene-modified cells could be detected in peripheral blood, lymph nodes, and bone marrow throughout the 1-year follow-up, and marking levels correlated with the cell dose. No significant changes of viral load were observed during the first 4 months. Four of the seven patients who changed their antiviral drug regimen thereafter responded with a significant decline in plasma viral load. In conclusion, the transfer of gene-modified cells was safe, led to sustained levels of gene marking, and may improve immune competence in HIV-infected patients with advanced disease and multidrug-resistant virus.