Undetectable viral load and HIV transmission dynamics on an individual and population level: where next in the global HIV response?

PURPOSE OF REVIEW: To examine recent literature on the efficacy and effectiveness of HIV treatment in preventing HIV transmission through sexual exposure, at both an individual and at a population level. RECENT FINDINGS: Two recent studies on the individual-level efficacy of treatment as prevention (TasP) have added to the now conclusive evidence that HIV cannot be transmitted sexually when the virus is suppressed. However, four large cluster-randomized population-level trials on universal HIV testing and treatment in Africa have not delivered the expected impact in reducing HIV incidence at a population level. Two of these trials showed no differences in HIV incidence between the intervention and control arms, one demonstrated a nonsignificant lower incidence in the intervention arm, and the fourth trial found a reduction between the communities receiving a combination prevention package and the control arm, but no difference between the immediate treatment plus the prevention package and the control arm. Factors contributing to the disconnect between individual high-level efficacy and population-level effectiveness of TasP include undiagnosed infection, delays in linkage to care, challenges in retention and adherence to antiretroviral therapy (ART), time between ART initiation and viral suppression, and stigma and discrimination. SUMMARY: Suppressive ART renders people living with HIV sexually noninfectious. However, epidemic control is unlikely to be achieved by TasP alone

Non-Disclosure of HIV Status and Associations with Psychological Factors, ART Non-Adherence, and Viral Load Non-Suppression Among People Living with HIV in the UK

Disclosure of HIV status to family, friends, and a stable partner may be linked to improved health outcomes for people living with HIV. This study assessed whether non-disclosure is associated with psychological symptoms, non-adherence to antiretroviral therapy (ART), and viral load (VL) non-suppression. A total of 3258 HIV-diagnosed individuals in the UK completed the confidential ASTRA study questionnaire (2011-2012). Participants reported whether they told anyone they had HIV; to which confidant(s) (friends, family, work colleagues, stable partner) and to what extent (none, some, most/all). The prevalence and factors associated with non-disclosure were assessed. Associations between non-disclosure and the following factors were established using modified Poisson regression with adjustment for socio-demographic factors (gender, age group, ethnicity), HIV-related factors (time since HIV diagnosis, ART status), and clinic: low social support (score ≤ 12 on modified Duke-UNC FSSQ); depression and anxiety symptoms (≥10 on PHQ-9 and GAD-7 respectively); self-reported ART non-adherence in past 2 weeks/3 months; VL non-suppression (clinic-recorded VL > 50 copies/mL among those who started ART ≥ 6 months ago). Among 3233 participants with disclosure data, the prevalence of non-disclosure to anyone was 16.6 % (n/N = 61/367) among heterosexual men, 15.7 % (98/626) among women, and 5.0 % (113/2240) among MSM. MSM were more likely to disclose to some/all friends compared to family (85.8 vs. 59.9 %) while heterosexuals were less likely to disclose to friends than family (44.1 vs. 61.1 % for men, 57.5 vs. 67.1 % for women). Among 1,631 participants with a stable partner, non-disclosure to a stable partner was 4.9 % for MSM, 10.9 % for heterosexual men, and 13.0 % for women. In adjusted analyses, older age (≥60 years), non-white ethnicity, more recent HIV diagnosis, and not having a stable partner were significantly associated with overall non-disclosure for MSM and heterosexual individuals. The prevalence of low social support was 14.4 %, of depression and anxiety symptoms 27.1 and 22.0 %, respectively, of ART non-adherence 31.8 %, and of viral load non-suppression on ART 9.8 %. There was no evidence that non-disclosure overall (versus disclosure to anyone) was associated with low social support, depression or anxiety symptoms, ART non-adherence or VL non-suppression among MSM or heterosexual individuals. However, compared to MSM who disclosed to 'none' or 'some' friends and family, MSM who disclosed to 'most or all' of their friends and family were more likely to have symptoms of depression (adjusted PR = 1.4, 95 % CI 1.2-1.7), anxiety (1.3, 1.1-1.6), and to report ART non-adherence (1.3, 1.1-1.5). In this large multicentre study of people living with HIV in the UK, non-disclosure was overall low, but higher for heterosexual individuals compared to MSM. Non-disclosure was not associated with higher prevalence of adverse health measures

Cirrhosis and liver transplantation in patients co-infected with HIV and hepatitis B or C: an observational cohort study

This study assessed the likelihood of referral for liver transplantation assessment in a prospective cohort of patients co-infected with HIV and hepatitis B or C with complications of cirrhosis. There were 141 co-infected patients from 11 UK centres with at least one complication of cirrhosis recorded (either decompensation or hepatocellular carcinoma) out of 772 identified with cirrhosis and/or HCC. Only 23 of these 141 (16.3%) were referred for liver transplantation assessment, even though referral is recommended for co-infected patients after the first decompensation episode

Health-state utilities in a prisoner population : a cross-sectional survey

Background: Health-state utilities for prisoners have not been described. Methods: We used data from a 1996 cross-sectional survey of Australian prisoners (n = 734). Respondent-level SF-36 data was transformed into utility scores by both the SF-6D and Nichol's method. Socio-demographic and clinical predictors of SF-6D utility were assessed in univariate analyses and a multivariate general linear model. Results: The overall mean SF-6D utility was 0.725 (SD 0.119). When subdivided by various medical conditions, prisoner SF-6D utilities ranged from 0.620 for angina to 0.764 for those with none/mild depressive symptoms. Utilities derived by the Nichol's method were higher than SF-6D scores, often by more than 0.1. In multivariate analysis, significant independent predictors of worse utility included female gender, increasing age, increasing number of comorbidities and more severe depressive symptoms. Conclusion: The utilities presented may prove useful for future economic and decision models evaluating prison-based health programs

Low intensity transcranial magnetic stimulation modulates skilled motor learning in adult mice

Repetitive transcranial magnetic stimulation (rTMS) is commonly used to modulate cortical plasticity in clinical and non-clinical populations. Clinically, rTMS is delivered to targeted regions of the cortex at high intensities (>1 T). We have previously shown that even at low intensities, rTMS induces structural and molecular plasticity in the rodent cortex. To determine whether low intensity rTMS (LI-rTMS) alters behavioural performance, daily intermittent theta burst LI-rTMS (120 mT) or sham was delivered as a priming or consolidating stimulus to mice completing 10 consecutive days of skilled reaching training. Relative to sham, priming LI-rTMS (before each training session), increased skill accuracy (~9%) but did not alter the rate of learning over time. In contrast, consolidating LI-rTMS (after each training session), resulted in a small increase in the rate of learning (an additional ~1.6% each day) but did not alter the daily skill accuracy. Changes in behaviour with LI-rTMS were not accompanied with long lasting changes in brain-derived neurotrophic factor (BDNF) expression or in the expression of plasticity markers at excitatory and inhibitory synapses for either priming or consolidation groups. These results suggest that LI-rTMS can alter specific aspects of skilled motor learning in a manner dependent on the timing of intervention

How have guidelines on when to start antiretroviral therapy affected survival of people living with HIV infection?

Purpose of review: Until recently, conflicting data led to discrepancies in guideline recommendation on ‘when to start’ antiretroviral therapy (ART) in asymptomatic HIV infection. This review focuses on evidence underpinning guidelines over the past decade and recent randomized clinical trial data in this area, which definitively informed the debate. Recent findings: In 2015, the landmark START trial demonstrated clear clinical benefit in terms of a reduction in serious AIDS and non-AIDS-related events and death from any cause in HIV-positive individuals randomized to start ART with a CD4 count more than 500 cells/µl compared with deferring starting until CD4 count declined to 350 cells/µl. Further, randomized clinical trial data were also available from the Temprano trial in Côte D’Ivoire which also demonstrated a reduced risk of death associated with earlier ART initiation. Summary: Following the results of the START trial, guidelines that had previously set CD4 thresholds for treatment initiation were universally changed. This is likely to reduce mortality in people living with HIV who are diagnosed early and have immediate access to ART. However, unless HIV testing rates and ART coverage are increased globally, raising the threshold for initiation of ART in clinical guidelines may be of limited benefit in reducing mortality in HIV

Patterns of sexualised recreational drug use and its association with risk behaviours and sexual health outcomes in men who have sex with men in London, UK: a comparison of cross-sectional studies conducted in 2013 and 2016

Objective: London has one of the highest identified prevalence of chemsex (sexualised recreational drug use) among men who have sex with men (MSM) in Europe. We examine MSM’s patterns of chemsex and its association with HIV/STI risk behaviours, STI diagnoses, and sexual healthcare-seeking behaviours, including if HIV testing behaviour met UK national guidelines (3-monthly if engaging in chemsex). Methods: Cross-sectional survey data from 2013 (n=905) and 2016 (n=739) were collected using anonymous, self-administered questionnaires from MSM recruited in commercial gay venues in London, UK. Descriptive and multivariable analyses, stratified by self-reported HIV status, were conducted. Adjusted prevalence ratios (aPR) with 95% confidence intervals (CI) were calculated. Results: Comparing the 2013 and 2016 surveys; chemsex prevalence in the past year remained stable, in both HIV-negative/unknown-status MSM (20.9% in 2013 vs 18.7% in 2016, p=0.301) and HIV-positive MSM (41.6% in 2013 vs 41.7% in 2016, p=0.992). Combined 2013-2016 data showed that compared to other MSM, those reporting chemsex were more likely to report HIV/STI risk behaviours, including condomless anal intercourse with serodifferent HIV-status partners (HIV-negative/unknown-status men: aPR 2.36, 95% CI 1.68-3.30; HIV-positive men: aPR 4.19, 95% CI 1.85-9.50), and STI diagnoses in the past year (HIV-negative/unknown-status men: aPR 2.10, 95% CI 1.64-2.69; HIV-positive men: aPR 2.56, 95% CI 1.57-4.20). 69.0% of HIV-negative/unknown-status men reporting chemsex attended sexual health clinics and 47.6% had tested for HIV more than once in the past year. Conclusions: Chemsex in London MSM remained stable but high, particularly among HIV-positive men. Irrespective of HIV status, chemsex was associated with engagement in HIV/STI risk behaviours. Frequency of HIV testing in the past year among HIV-negative/unknown-status men was below national recommendations. Promoting combination prevention strategies, including 3-monthly HIV/STI testing, access to PrEP/ART, and behavioural interventions among MSM reporting chemsex, remain vital to address sexual health inequalities in MSM

Determinants of assault-related violence in the community: potential for public health interventions in hospitals.

Data from emergency departments (EDs) in England describe the epidemiology of violent assaults. However, the potential of such data to inform hospital-based public health interventions remains unknown

Is Sustained Virological Response a Marker of Treatment Efficacy in Patients with Chronic Hepatitis C Viral Infection with No Response or Relapse to Previous Antiviral Intervention?

Background: Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs.  Methods: We created a decision tree model based on a Cochrane systematic review on interferon retreatment for patients who did not respond to initial therapy or who relapsed following SVR. Extrapolating data to 20 years, we modelled the outcome from three scenarios: (1) observed medium-term (5 year) annual mortality rates continue to the long term (20 years); (2) long-term annual mortality in retreatment responders falls to that of the general population while retreatment non-responders continue at the medium-term mortality; (3) long-term annual mortality in retreatment non-responders is the same as control group non-responders (i.e., the increased treatment-related medium mortality “wears off”).  Results: The mean differences in life expectancy over 20 years with interferon versus control in the first, second, and third scenarios were -0.34 years (95% confidence interval (CI) -0.71 to 0.03), -0.23 years (95% CI -0.69 to 0.24), and -0.01 (95% CI -0.3 to 0.27), respectively. The life expectancy was always lower in the interferon group than in the control group in scenario 1. In scenario 3, the interferon group had a longer life expectancy than the control group only when more than 7% in the interferon group achieved SVR.  Conclusions: SVR may be a good prognostic marker but does not seem to be a valid surrogate marker for assessing HCV treatment efficacy of interferon retreatment. The SVR threshold at which retreatment increases life expectancy may be different for different drugs depending upon the adverse event profile and treatment efficacy. This has to be determined for each drug by RCTs and appropriate modelling before SVR can be accepted as a surrogate marker