HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia.

Russia has one of the largest and fastest growing HIV epidemics. However, epidemiological data are scarce. Sub-subtype A6 is most prevalent in Russia but its identification is challenging. We analysed protease/reverse transcriptase-, integrase-sequences, and epidemiological data from 303 patients to develop a methodology for the systematisation of A6 identification and to describe the HIV epidemiology in the Russian Southern Federal District. Drug consumption (32.0%) and heterosexual contact (27.1%) were the major reported transmission risks. This study successfully established the settings for systematic identification of A6 samples. Low frequency of subtype B (3.3%) and large prevalence of sub-subtype A6 (69.6%) and subtype G (23.4%) were detected. Transmitted PI- (8.8%) and NRTI-resistance (6.4%) were detected in therapy-naive patients. In therapy-experienced patients, 17.3% of the isolates showed resistance to PIs, 50.0% to NRTI, 39.2% to NNRTIs, and 9.5% to INSTIs. Multiresistance was identified in 52 isolates, 40 corresponding to two-class resistance and seven to three-class resistance. Two resistance-associated-mutations significantly associated to sub-subtype A6 samples: A62VRT and G190SRT. This study establishes the conditions for a systematic annotation of sub-subtype A6 to normalise epidemiological studies. Accurate knowledge on South Russian epidemiology will allow for the development of efficient regional frameworks for HIV-1 infection management.

Longitudinal comparison of HIV-1 plasma viral load and cellular proviral load.

INTRODUCTION: The goal of antiretroviral treatment (ART) in HIV-1 infection is the permanent suppression of plasma viral load (pVL) below the currently existing limit of detection of 50 copies/mL (DAIG HIV-therapy guidelines). Therefore, treatment effectiveness is based on pVL. pVL measurements however do not give any information about the viral reservoir in peripheral blood mononuclear cells (PBMCs). Therefore, the proviral DNA of HIV-1 could be a useful marker for the investigation of viral reservoirs and monitoring ART in patients showing undetectable pVL. MATERIALS AND METHODS: Seventy-seven treatment-experienced HIV-1 infected patients with pVL <50 copies/mL were randomly selected. pVL and proviral DNA load were measured using the Roche COBAS TaqMan HIV-1 v2.0 assay. Additionally, CD4+ cell count per mL and the total white blood cell (wbc) count per mL were determined for each patient. Follow-up data were collected 24 weeks after the time point of the first measurement. Proviral DNA load per mL, CD4+ cell count per mL as well as wbc count per mL were observed over time and differences were estimated using the Mann-Whitney U test. Additionally, correlations between the clinical parameters were analyzed using the two-sided Pearson correlation analysis. RESULTS: Out of the 77 patients, 38 show a significant increase in proviral load per mL over time (p=0,001), whereas 39 patients show a significant decrease (p=0,001). No differences became visible in the CD4+ cell count per mL comparing week 0 and week 24 data. Thirty five patients show a significant increase in wbc count per mL over time (p<0,001), while 42 patients show a significant decrease (p<0,001). A significant correlation of increasing proviral load per mL and wbc count per mL for data of the first (p<0.001) and the second measurement (p<0.001) can be detected, while there are no correlations found between proviral load per mL and CD4+ cell count per mL. CONCLUSIONS: Our data show that the presence of viral reservoirs in other cell types and not only CD4+ cells is most probable. HIV-1 proviral DNA seems to be an interesting marker in patients with undetectable pVL and allows the assessment of replication under ART. Nevertheless, further longitudinal studies are needed to assess the usefulness and the clinical significance of this marker.