Switching Virally Suppressed, Treatment-Experienced Patients to a Raltegravir-Containing Regimen Does Not Alter Levels of HIV-1 DNA

Background: Current HIV-1 antiretroviral therapy (ART) greatly reduces virus replication but does not significantly affect the viral reservoir. Raltegravir, a recently introduced integrase inhibitor, could, at least theoretically, reduce residual viremia in patients on ART and affect the viral reservoir size. The aim of this study was to assess whether switching therapy in treatment-experienced patients that were virally suppressed to a raltegravir-containing regimen reduces the size of the viral reservoir, and if such treatment leads to a change in levels of HIV 2-LTR circles in this patient group. Methods: 14 ART experienced individuals with a suppressed viral load (,50 HIV-1 RNA copies/mL plasma) at baseline (for at least 2 months) were switched to a raltegravir-containing regimen. Blood samples were taken at baseline and at $2 timepoints up to 4866 weeks. Levels of total HIV-1 DNA and 2-LTR circles in peripheral blood mononuclear cells (PBMCs) were measured using real-time PCR assays. Results: There was no significant change in HIV-1 total DNA levels over the study duration (p = 0.808), median slope 0.24 (conservative nonparametric 95 % CI: 211.78, 26.23). Low levels of 2-LTR circles were detected in 2 patients. One had 16 copies/10 6 PBMCs at baseline and the other had 34 copies/10 6 PBMCs at week 51. Conclusions: The switch to a raltegravir containing regimen was not associated with a significant change in HIV-1 total DNA levels in this cohort. There were no observed changes in the levels of HIV-1 2-LTR circles associated with raltegravi

The impact of the mode of survey administration on estimates of daily smoking for mobile phone only users

Background: Over the past decade, there have been substantial changes in landline and mobile phone ownership, with a substantial increase in the proportion of mobile-only households. Estimates of daily smoking rates for the mobile phone only (MPO) population have been found to be substantially higher than the rest of the population and telephone surveys that use a dual sampling frame (landline and mobile phones) are now considered best practice. Smoking is seen as an undesirable behaviour; measuring such behaviours using an interviewer may lead to lower estimates when using telephone based surveys compared to self-administered approaches. This study aims to assess whether higher daily smoking estimates observed for the mobile phone only population can be explained by administrative features of surveys, after accounting for differences in the phone ownership population groups. Methods: Data on New South Wales (NSW) residents aged 18 years or older from the NSW Population Health Survey (PHS), a telephone survey, and the National Drug Strategy Household Survey (NDSHS), a self-administered survey, were combined, with weights adjusted to match the 2013 population. Design-adjusted prevalence estimates and odds ratios were calculated using survey analysis procedures available in SAS 9.4. Results: Both the PHS and NDSHS gave the same estimates for daily smoking (12%) and similar estimates for MPO users (20% and 18% respectively). Pooled data showed that daily smoking was 19% for MPO users, compared to 10% for dual phone owners, and 12% for landline phone only users. Prevalence estimates for MPO users across both surveys were consistently higher than other phone ownership groups. Differences in estimates for the MPO population compared to other phone ownership groups persisted even after adjustment for the mode of collection and demographic factors. Conclusions: Daily smoking rates were consistently higher for the mobile phone only population and this was not driven by the mode of survey collection. This supports the assertion that the use of a dual sampling frame addresses coverage issues that would otherwise be present in telephone surveys that only made use of a landline sampling frame

Nouvelles de l'archéologie

Objectives: To examine the relationship between human leukocyte antigen (HLA) genotype and body composition changes induced by thymidine analogue nucleoside reverse transcriptase inhibitor (NtRTI) use in HIV-positive individuals. Design: Data collected during the Simplification with Tenofovir-Emtricitabine (TDF-FTC) or Abacavir-Lamivudine (ABC-3TC) (STEAL) study were analysed to examine the potential association of HLA genotypes with changes in body composition in treatment-experienced HIV-positive individuals. Methods: Demographic, HIV-related, body composition and HLA genotyping data from the STEAL study were used in this analysis. The mean percentage peripheral fat at study baseline was compared in participants with and without prior NtRTI use. Analyses were also carried out for each HLA supertype strata, for five HLA genes, within the thymidine-exposed group. These comparisons were made using Mann-Whitney rank-sum tests. Results: Participants with prior NtRTI use had a significantly lower baseline mean peripheral fat percentage compared to those without NtRTI use (31.9 vs. 34.7%; P = 0.0045). However, participants carrying one or more of the three particular HLA supertype alleles, A01, B08 and DQ2, showed no significant difference in mean peripheral fat percentage at baseline by NtRTI use. Among participants with prior NtRTI exposure, there were significant differences in mean peripheral fat by HLA A01, B08 and DQ2 allele expression compared to those without expression of these alleles (A01: 34.91% vs. no A01: 30.3%; P = 0.0087; B08: 36.2% vs. no B08: 31.1%; P = 0.0317; DQ2: 35.16% vs. no DQ2: 30.06%; P = 0.0081). Conclusion: This analysis suggests that HIV-infected individuals carrying HLA A01, B08 or DQ2 supertype alleles may be resistant to NtRTI-induced peripheral fat loss

HLA alleles association with changes in bone mineral density in HIV-1-infected adults changing treatment to Tenofovir-Emtricitabine or Abacavir-Lamivudine

Background: There are limited data regarding the influence of human leukocyte antigen (HLA) polymorphisms on reduced bone mineral density (BMD). We investigated the relationship between HLA supertypes and BMD in HIV-infected adults changing their existing treatment to tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine (ABC-3TC) in the STEAL study. Methods: Lumbar spine and right hip BMD were measured by Dual-energy X-ray absorptiometry (DXA). HLA genotypes at the 2-digit level were classified into class I and II supertypes. Student’s t-tests were used to test the association between HLA supertypes and changes in hip and spine BMD over 96 weeks for the whole cohort and stratified by randomised groups. The relationship between HLA supertypes and BMD was also assessed in the subgroup of participants that were naı¨ve to both ABC and TDF at study entry. Results: Class II supertypes were mainly associated with hip BMD change. Overall, compared to participants not carrying HLA-DQ3, participants expressing DQ3 had less bone loss over 96 weeks at both the hip and spine (hip: 0.003 vs. –0.006 g/ cm², 95%CI 0.002 to 0.017, p = 0.016; spine: 0.006 vs. –0.006 g/cm², 95%CI 0.001 to 0.023, p = 0.041). In participants that were naïve to both ABC and TDF at baseline and randomised to TDF-FTC, DQ3 was significantly associated with less bone loss compared with those not carrying DQ3 (hip: 0.001 vs. –0.032 g/cm²; diff 0.033; 95%CI 0.017 to 0.049; p,0.001; spine: 0.007 vs. –0.023 g/cm²; diff 0.035; 95%CI 0.014 to 0.056; p = 0.001).Hila Haskelberg, Damien V. Cordery, Janaki Amin, Anthony D. Kelleher, David A. Cooper, Sean Emery, on behalf of the STEAL Study Grou

Patient disposition.

<p>* Some patients were ineligible for more than one reason.</p

Absolute change over 96 weeks in hip BMD by HLA-DQ3 supertype and randomisation in participants naïve to both ABC and TDF at study entry.

<p>Absolute change over 96 weeks in hip BMD by HLA-DQ3 supertype and randomisation in participants naïve to both ABC and TDF at study entry.</p

Baseline characteristics.

<p>Results are expressed as mean ± standard deviation or %.</p><p>Abbreviations: ABC-3TC, abacavir-lamivudine; HLA, human leukocyte antigen; TDF-FTC, tenofovir-emtricitabine; NRTI, Nucleoside Reverse Transcriptase Inhibitor.</p