The relevance of ultradeep sequencing for low HIV-1 viral loads and proviruses in the clinical setting.

Improving the therapeutic management of HIV-positive persons is a major public health issue and includes better detection of drug resistance mutations (DRMs). The aim of this study was (i) to explore DRMs in HIV-1-positive persons presenting a blood viral load (VL) < 1000 genomes copies (gc)/mL, including the analyze of cerebrospinal fluid (CSF) and HIV-DNA from peripheral blood mononuclear cells using ultradeep sequencing (UDS) and (ii), to evaluate how these DRMs could influence the clinical practices. For each patient (n = 12), including five low-VL patients (i.e., <1000 gc/mL), HIV-1 UDS targeting the protease, reverse transcriptase and integrase genes was performed on plasma, proviral DNA, and CSF when available. Sequencing discordances or failures were mostly found in samples from low-VL patients. A 5% UDS cut-off allowed to increase the sensitivity to detect DRMs in different compartments, excepted in CSF. Patients with the highest viral quasispecies heterogeneity were naïve of treatment or presented a medical history suggesting low selection pressure or virological failures. When analyzing compartmentalization and following-up patients: low-frequency variants (LFVs) were responsible for 47% (n = 8) and 76% (n = 13) of changes in drug resistance interpretation, respectively. In such cases, we conclude that UDS is a robust technique, which still could be improved by increase the RNA and/or DNA extraction in low-VL samples to detect LFVs. Further studies are needed to define the impact of LFVs on antiretroviral treatments. At last, when considering a DRM, the use of mutational load would probably be more suitable than frequencies.

[Assessing the implementation of the 2010-2014 National Plan against HIV in the Regional Coordination Centers for the Fight against HIV (COREVIHs)]. / Déclinaison du plan national de lutte contre le VIH 2010/2014 au sein des COREVIH.

INTRODUCTION: In France, 50,000 people are unaware of their HIV status because they have not been screened. Every year, there are nearly 7,000 new HIVinfections. To address this issue, the French Ministry of Health and Sport published the 2010-2014 National Plan against HIV/AIDS and other sexually transmitted diseases. A national survey was conducted among the Regional Coordination Centers for the Fight against HIV (COREVIHs) to assess their views of the National Plan and their current funding levels. METHOD: A questionnaire was sent to the presidents and coordinators of the 28 COREVIHs. RESULTS: After two reminders, 19 of the 28 COREVIHs responded. The National Plan was the original impetus for an assessmentofcurrent practices, accompanied by the implementation ofnew measures and new working groups. There is evidence that the COREVIHs are committed to developing incentive measures to promote screening and that they are also working to coordinate regional training programs in the area of screening and testing. The assessment also found that 11 COREVIHs were considering a reorganization of the CDAG/CIDDIST centers (CDAG: Free Anonymous Testing Center/ CIDDIST: STI Information, Testing and Diagnosis Center). Some COREVIHs have been involved in coordinating therapeutic education at a regional level. Most COREVIHs are also actively involved in the fight against discrimination. However, a number of obstacles to the implementation of the plan were identified. DISCUSSION: The purpose of this study was to examine the involvement of the COREVIHs in the implementation of the 2010-2014 National Plan against HIV The results indicate that implementing a system involving a specific form ofregionalcoordination of a public health problem is possible and should provide a basis for the decentralized implementation of public health plans.

Treatment as prevention enrolling at least 75% of individuals on ART will be needed to significantly reduce HIV prevalence in a HIV cohort.

BACKGROUND: "Treatment as Prevention" (TasP) aims to reduce new HIV infections through higher enrolment on suppressive antiretroviral therapy (ART). OBJECTIVES: We studied the current epidemic and possible impact of TasP in a French HIV cohort including MSM and migrant subjects. STUDY DESIGN: Socio-demographic, clinical and laboratory variables were collected during the follow-up of 6995 HIV-infected patients. The numbers of individuals living with HIV in each year were estimated from diagnoses up to that year minus recorded deaths. Patients were classified according to gender, transmission mode, country of birth and treatment status. RESULTS: The cohort includes 6995 individuals diagnosed from 1985 to 2015, of whom 72% were men. Unprotected sexual intercourse was the main mode of transmission. Women were more likely to be migrants (45% versus 13%), whereas men were more likely to have been born in France (52% versus 27%). Diagnoses were more correlated with untreated than treated prevalence in each group. MSM diagnoses was strongly correlated to untreated prevalence whatever the country of birth (p < 0.0001). However, heterosexual diagnoses were better correlated with prevalence within individual country groups (b = 0.29 female diagnoses/year per untreated male born in France, compared to b = 0.73 for foreigners). Using these transmission rates, mathematical modelling estimated that enrolling 75% of untreated individuals per year would decrease diagnoses ten-fold by 2021. CONCLUSIONS: Enrolling at least 75% of individuals on ART is necessary to substantially impact numbers of new HIV infections in this cohort. Treatment as prevention will actually be effective to reduce HIV prevalence.

Is total community viral load a robust predictive marker of the efficacy of the TasP strategy?

A mild but significant association between a decrease in the total community viral load (CVL) and a decrease in the number of new HIV diagnoses was observed between 2005 and 2010 in the population of northern and eastern France. This result suggests that CVL could be used as robust marker of the efficacy of the "Treatment as Prevention" strategy, and it may even be stronger if a large number of undiagnosed patients and early HIV infection cases indicated by extend screening are included in the CVL measurement.