Simon Collins

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

BACKGROUND Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause. RESULTS A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. CONCLUSIONS The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.).

British HIV Association guidelines for HIV‐associated malignancies 2014

M Bower, S Collins, C Cottrill, K Cwynarski, S Montoto, M Nelson, N Nwokolo, T Powles, J Stebbing, N Wales and A Webb, on behalf of the AIDS Malignancy Subcommittee Department of Oncology, Chelsea & Westminster Hospital, London, UK, HIV i-Base and UK-CAB, London, UK, St Bartholomew’s Hospital, London, UK, Royal Free Hospital, London, UK, Hammersmith Hospital, London, UK and Royal Sussex County Hospital, Brighton, UK

Recreational drug use, polydrug use, and sexual behaviour in HIV-diagnosed men who have sex with men in the UK: results from the cross-sectional ASTRA study

BACKGROUND Recreational drug use in men who have sex with men (MSM) is of concern because it might be linked to the transmission of HIV and other sexually transmitted infections. Evidence about drug use in HIV-diagnosed MSM in the UK is limited by representativeness of the study populations. We describe patterns of drug use and associations with sexual behaviours in HIV-diagnosed MSM in the UK. METHODS We used data from the cross-sectional ASTRA study, which recruited participants aged 18 years or older with HIV from eight HIV outpatient clinics in the UK between Feb 1, 2011, and Dec 31, 2012. We examined data for MSM, assessing the prevalence of recreational drug use and polydrug use in the previous 3 months and associations with sociodemographic and HIV-related factors. We examined the association of polydrug use with measures of condomless sex in the previous 3 months and with other sexual behaviours. FINDINGS Our analysis included data for 2248 MSM: 2136 (95%) were gay, 1973 (89%) were white, 1904 (85%) were on antiretroviral treatment (ART), and 1682 (76%) had a viral load of 50 copies per mL or lower. 1138 (51%) used recreational drugs in the previous 3 months; 608 (27%) used nitrites, 477 (21%) used cannabis, 460 (21%) used erectile dysfunction drugs, 453 (20%) used cocaine, 280 (13%) used ketamine, 258 (12%) used 3,4-methylenedioxy-N-methylamphetamine (MDMA), 221 (10%) used gamma-hydroxybutyrate or gamma-butyrolactone, 175 (8%) used methamphetamine, and 162 (7%) used mephedrone. In the 1138 individuals who used drugs, 529 (47%) used three or more drugs and 241 (21%) used five or more. Prevalence of injection drug use was 3% (n = 68). Drug use was independently associated with younger age (p < 0·0001), not being religious (p = 0·001), having an HIV-positive stable partner (p = 0·0008), HIV-serostatus disclosure (p = 0·009), smoking (p < 0·0001), evidence of harmful alcohol drinking (p = 0·0001), and ART non-adherence (p < 0·0001). Increasing polydrug use was associated with increasing prevalence of condomless sex (prevalence range from no drug use to use of five or more drugs was 24% to 78%), condomless sex with HIV-seroconcordant partners (17% to 69%), condomless sex with HIV-serodiscordant partners (10% to 25%), and higher-HIV-risk condomless sex after taking viral load into account (4% to 16%; p ≤ 0·005 for all). Associations were similar after adjustment for sociodemographic and HIV-related factors. Methamphetamine was more strongly associated with higher-HIV-risk condomless sex than were other commonly used drugs. INTERPRETATION Polydrug use is prevalent in HIV-diagnosed MSM and is strongly associated with condomless sex. Specialist support services for MSM with HIV who use recreational drugs might be beneficial in the reduction of harm and prevention of ongoing transmission of HIV and other sexually transmitted infections. FUNDING National Institute for Health Research.

Health-related quality-of-life of people with HIV in the era of combination antiretroviral treatment: a cross-sectional comparison with the general population

BACKGROUND Combination antiretroviral therapy has substantially increased life-expectancy in people living with HIV, but the effects of chronic infection on health-related quality of life (HRQoL) are unclear. We aimed to compare HRQoL in people with HIV and the general population. METHODS We merged two UK cross-sectional surveys: the ASTRA study, which recruited participants aged 18 years or older with HIV from eight outpatient clinics in the UK between Feb 1, 2011, and Dec 31, 2012; and the Health Survey for England (HSE) 2011, which measures health and health-related behaviours in individuals living in a random sample of private households in England. The ASTRA study has data for 3258 people (response rate 64%) and HSE for 8503 people aged 18 years or older (response rate 66%). HRQoL was assessed with the Euroqol 5D questionnaire 3 level (EQ-5D-3L) instrument that measures health on five domains, each with three levels. The responses are scored on a scale where a value of 1 represents perfect health and a value of 0 represents death, known as the utility score. We used multivariable models to compare utility scores between the HIV and general population samples with adjustment for several sociodemographic factors. FINDINGS 3151 (97%) of 3258 of participants in ASTRA and 7424 (87%) of 8503 participants in HSE had complete EQ-5D-3L data. The EQ-5D-3L utility score was lower for people with HIV compared with that in the general population (marginal effect in utility score adjusted for age, and sex/sexuality -0·11; 95% CI -0·13 to -0·10; p < 0·0001). HRQoL was lower for people with HIV for all EQ-5D-3L domains, particularly for anxiety/depression. The difference in utility score was significant after adjustment for several additional sociodemographic variables (ethnic origin, education, having children, and smoking status) and was apparent across all CD4 cell count, antiretroviral therapy, and viral load strata, but was greatest for those people diagnosed with HIV in earlier calendar periods. Reduction in HRQoL with age was not greater in people with HIV than in the general population (pinteraction > 0·05). INTERPRETATION People living with HIV have significantly lower HRQoL than do the general population, despite most HIV positive individuals in this study being virologically and immunologically stable. Although this difference could in part be due to factors other than HIV, this study provides additional evidence of the loss of health that can be avoided through prevention of further HIV infections. FUNDING UK National Institute for Health Research.

Poly drug use, chemsex drug use, and associations with sexual risk behaviour in HIV-negative men who have sex with men attending sexual health clinics

BACKGROUND Recreational drug use and associated harms continue to be of significant concern in men who have sex with men (MSM) particularly in the context of HIV and STI transmission. METHODS Data from 1484 HIV-negative or undiagnosed MSM included in the AURAH study, a cross-sectional, self-completed questionnaire study of 2630 individuals from 20 sexual health clinics in the United Kingdom in 2013-2014, was analysed. Two measures of recreational drug use in the previous three months were defined; (i) polydrug use (use of 3 or more recreational drugs) and (ii) chemsex drug use (use of mephedrone, crystal methamphetamine or GHB/GBL). Associations of socio-demographic, health and lifestyle factors with drug use, and associations of drug use with sexual behaviour, were investigated. RESULTS Of the 1484 MSM, 350 (23.6%) reported polydrug use and 324 (21.8%) reported chemsex drug use in the past three months. Overall 852 (57.5%) men reported condomless sex in the past three months; 430 (29.0%) had CLS with ≥2 partners, 474 (31.9%) had CLS with unknown/HIV+ partner(s); 187 (12.6%) had receptive CLS with an unknown status partner. For polydrug use, prevalence ratios (95% confidence interval) for association with CLS measures, adjusted for socio-demographic factors were: 1.38 (1.26, 1.51) for CLS; 2.11 (1.80, 2.47) for CLS with ≥2 partners; 1.89 (1.63, 2.19) for CLS with unknown/HIV+ partner(s); 1.36 (1.00, 1.83) for receptive CLS with an unknown status partner. Corresponding adjusted prevalence ratios for chemsex drug use were: 1.38 (1.26, 1.52); 2.07 (1.76, 2.43); 1.88 (1.62, 2.19); 1.49 (1.10, 2.02). Polydrug and chemsex drug use were also strongly associated with previous STI, PEP use, group sex and high number of new sexual partners. Associations remained with little attenuation after further adjustment for depressive symptoms and alcohol intake. CONCLUSION There was a high prevalence of polydrug use and chemsex drug use among HIV negative MSM attending UK sexual health clinics. Drug use was strongly associated with sexual behaviours linked to risk of acquisition of STIs and HIV.

Minimal Cognitive Impairment in UK HIV Positive Men Who Have Sex with Men: Effect of Case Definitions, and Comparison with the General Population and HIV Negative Men.

Background:To determine the prevalence of neurocognitive impairment (NCI) in UK HIV-positive and HIV-negative men who have sex with men (MSM). Methods:HIV-positive and HIV-negative participants were recruited to a cross-sectional study from 2 London clinics and completed computer-assisted neuropsychological tests and questionnaires of depression, anxiety, and activities of daily living. Published definitions of HIV-associated neurocognitive disorders (HAND) and global deficit scores were used. Age- and education-adjusted neuropsychological test scores were directly compared with reference population data. Results:A total of 248 HIV-positive and 45 HIV-negative MSM participated. In the HIV-positive group, median time since diagnosis was 9.4 years, median CD4+ count was 550 cells per cubic millimeter, and 88% were on antiretroviral therapy. Prevalence of HAND was 21.0% in HIV-positive MSM (13.7% asymptomatic neurocognitive impairment, 6.5% mild neurocognitive disorder, and 0.8% HIV-associated dementia). Using a global deficit score threshold of 0.5, the prevalence of NCI was 31.5% (when averaged over 5 neuropsychological domains) and 40.3% (over 10 neuropsychological test scores). These results were not significantly different from the HIV-negative study sample. No consistent pattern of impairment was seen in HIV-positive patients relative to general male population data (n = 380). Conclusions:We found a prevalence of HAND and degree of impairment on neuropsychological testing of HIV-positive MSM that could represent a normal population distribution. These findings suggest that NCI may be overestimated in HIV-positive MSM, and that the attribution of NCI to HIV infection implied by the term HAND requires revision.

Potential impact on HIV incidence of higher HIV testing rates and earlier antiretroviral therapy initiation in MSM.

Background:Increased rates of testing, with early antiretroviral therapy (ART) initiation, represent a key potential HIV-prevention approach. Currently, in MSM in the United Kingdom, it is estimated that 36% are diagnosed by 1 year from infection, and the ART initiation threshold is at CD4+ cell count 350/&mgr;l. We investigated what would be required to reduce HIV incidence in MSM to below 1 per 1000 person-years (i.e. <535 new infections per year) by 2030, and whether this is likely to be cost-effective. Methods:A dynamic, individual-based simulation model was calibrated to multiple data sources on HIV in MSM in the United Kingdom. Outcomes were projected according to future alternative HIV testing and ART initiation scenarios to 2030, considering also potential changes in levels of condomless sex. Results:For ART use to result in an incidence of close to 1/1000 person-years requires the proportion of all HIV-positive MSM with viral suppression to increase from below 60% currently to 90%, assuming no rise in levels of condomless sex. Substantial increases in HIV testing, such that over 90% of men are diagnosed within a year of infection, would increase the proportion of HIV-positive men with viral suppression to 80%, and it would be 90%, if ART is initiated at diagnosis. The scenarios required for such a policy to be cost-effective are presented. Conclusion:This analysis provides targets for the proportion of all HIV-positive MSM with viral suppression required to achieve substantial reductions in HIV incidence.

The ‘Antiretrovirals, Sexual Transmission Risk and Attitudes’ (ASTRA) Study. Design, Methods and Participant Characteristics

Life expectancy for people diagnosed with HIV has improved dramatically however the number of new infections in the UK remains high. Understanding patterns of sexual behaviour among people living with diagnosed HIV, and the factors associated with having condom-less sex, is important for informing HIV prevention strategies and clinical care. In addition, in view of the current interest in a policy of early antiretroviral treatment (ART) for all people diagnosed with HIV in the UK, it is of particular importance to assess whether ART use is associated with increased levels of condom-less sex. In this context the ASTRA study was designed to investigate current sexual activity, and attitudes to HIV transmission risk, in a large unselected sample of HIV-infected patients under care in the UK. The study also gathered background information on demographic, socio-economic, lifestyle and disease-related characteristics, and physical and psychological symptoms, in order to identify other key factors impacting on HIV patients and the behaviours which underpin transmission. In this paper we describe the study rationale, design, methods, response rate and the demographic characteristics of the participants. People diagnosed with HIV infection attending 8 UK HIV out-patient clinics in 2011-2012 were invited to participate in the study. Those who agreed to participate completed a confidential, self-administered pen-and-paper questionnaire, and their latest CD4 count and viral load test results were recorded. During the study period, 5112 eligible patients were invited to take part in the study and 3258 completed questionnaires were obtained, representing a response rate of 64% of eligible patients. The study includes 2248 men who have sex with men (MSM), 373 heterosexual men and 637 women. Future results from ASTRA will be a key resource for understanding HIV transmission within the UK, targeting prevention efforts, and informing clinical care of individuals living with HIV.

Socioeconomic status and treatment outcomes for individuals with HIV on antiretroviral treatment in the UK: cross-sectional and longitudinal analyses

Summary Background Few studies have assessed the effect of socioeconomic status on HIV treatment outcomes in settings with universal access to health care. Here we aimed to investigate the association of socioeconomic factors with antiretroviral therapy (ART) non-adherence, virological non-suppression, and virological rebound, in HIV-positive people on ART in the UK. Methods We used data from the Antiretrovirals, Sexual Transmission Risk and Attitudes (ASTRA) questionnaire study, which recruited participants aged 18 years or older with HIV from eight HIV outpatient clinics in the UK between Feb 1, 2011, and Dec 31, 2012. Participants self-completed a confidential questionnaire on sociodemographic, health, and lifestyle issues. In participants on ART, we assessed associations of financial hardship, employment, housing, and education with: self-reported ART non-adherence at the time of the questionnaire; virological non-suppression (viral load >50 copies per mL) at the time of questionnaire in those who started ART at least 6 months ago (cross-sectional analysis); and subsequent virological rebound (viral load >200 copies per mL) in those with initial viral load of 50 copies per mL or lower (longitudinal analysis). Findings Of the 3258 people who completed the questionnaire, 2771 (85%) reported being on ART at the time of the questionnaire, and 2704 with complete data were included. 873 (32%) of 2704 participants reported non-adherence to ART and 219 (9%) of 2405 had virological non-suppression in cross-sectional analysis. Each of the four measures of lower socioeconomic status was strongly associated with non-adherence to ART, and with virological non-suppression (prevalence ratios [PR] adjusted for gender/sexual orientation, age, and ethnic origin: greatest financial hardship vs none 2·4, 95% CI 1·6–3·4; non-employment 2·0, 1·5–2·6; unstable housing vs homeowner 3·0, 1·9–4·6; non-university education 1·6, 1·2–2·2). 139 (8%) of 1740 individuals had subsequent virological rebound (rate=3·6/100 person-years). Low socioeconomic status was predictive of longitudinal rebound risk (adjusted hazard ratio [HR] for greatest financial hardship vs none 2·3, 95% CI 1·4–3·9; non-employment 3·0, 2·1–4·2; unstable housing vs homeowner 3·3, 1·8–6·1; non-university education 1·6, 1·1–2·3). Interpretation Socioeconomic disadvantage was strongly associated with poorer HIV treatment outcomes in this setting with universal health care. Adherence interventions and increased social support for those most at risk should be considered. Funding National Institute for Health Research.

Effects of age on symptom burden, mental health and quality of life amongst people with HIV in the UK

The evolving HIV epidemic, coupled with advances in HIV treatment, has resulted in an ageing HIV‐diagnosed population. It has been suggested that adverse physical and psychological effects of HIV may be higher among older people. However, few studies have examined the effect of older age on well‐being for people with HIV.