For the ASTRA Study Group Do socioeconomic factors explain gender differences in virological response to ART in the UK? R O’Connell, LS Burch, J Anderson, M Johnson, AM Geretti, AJ Rodger, L Sherr, R Gilson, N Perry, J Elford, M Jones, AN Phillips, A Speakman, FC Lampe, CJ Smith For the ASTRA Study Group

Gender and socioeconomic factors in HIV Biological Susceptibility, immune activation, disease progression compartmentalization, pregnancy, reproductive health Treatment Pharmacokinetics, pharmacodynamics, drug toxicities, viral load outcomes Socioeconomic Testing, access to care, retention in care, mental health and well-being, gender based violence, neighbourhood, food security, housing Research Equity of access: support, treatment and cure Loutfy MR et al. AIDS Soc 2013;16:18509 ; Rosin C, et al. HIV Med 2015;16(5):319-25; Zheng Yin et el UK Health Protection Directorate; Gueler A, et al. AIDS 2015;29(2):231-8.; Johnston RE, Heitzeg MM. AIDS Res Human Retrovir 2015;31(1):85-97; Hatcher AM, et al. AIDS 2015; 29(16):2183–2194

Gender and socioeconomic factors: UK Higher prevalence in socioeconomically vulnerable areas; MSW and women vs MSM test less in sexual health setting; higher prevalence in Black African Women vs men (71 vs 41 /1000); Black African MSW present late compared to all other groups1 Conflicting evidence for VL outcomes: no difference1,2; worse outcomes for women and MSW vs MSM3; higher VL failure for MSW vs women4 Socioeconomic stress factors associated with viral load rebound despite universal treatment access5 Zheng Yin et al HIV in the United Kingdom 2014 Report; Sherr L, et al. Women Health. 2012;52(3):214-33. Saunders P et al; HIV Med. 2015. Barber TJ et al Antiviral Ther 2011;16(6):805-14 Burch et al CROI 2015 Poster 560

Aims To assess whether socio-economic factors explain observed differences in virological outcomes in MSM and MSW and women in the ASTRA study

ASTRA study Self completed questionnaire survey of 3258 participants (64% response rate) in 8 clinics in the UK 2011-12 Demographic factors [gender/sexuality, age, ethnicity, stable partner, children, identifies with a religion] Socio-economic factors [UK birth/English fluency, financial status, employment, housing status, education, supportive network (modified Duke FSS questionnaire)] Current depression symptoms (PHQ-9) HIV-related and other health-related factors [time since HIV diagnosis, ART use, disclosure of HIV status, currently pregnant, IDU transmission route] Lifestyle factors [smoking, possible alcohol dependency (CAGE questionnaire), recreational drug use] 637 women 373 MSW (heterosexual men) 2248 MSM (gay/bisexual men) Longitudinal linkage to care with additional consent (N= 2983)

Statistical methods Cross sectional: CD4 and VL recorded by clinic at time of questionnaire Population: on ART, and started at least 6 months ago Virological outcome: VL >50 copies/ml Prevalence of VL>50 compared between MSM, MSW and women using modified Poisson regression Longitudinal: linkage with prospective clinic data for consenting participants (92%); data available for 6 clinics Population: on ART, and started at least 6 months ago with VL<50 copies/ml at time of questionnaire Viral rebound: first VL>200 copies/ml Rate of rebound compared between MSM, MSW and women using Cox Proportional Hazards regression

Baseline characteristics: MSM, MSW, women On ART started > 6 months ago N=2445 N (%/ median IQR) MSM N=1678 MSW N=285 Women N=482 p-value* Age <40 years 28% 20% 38% <0.001 White 89% 29% 19% <0.001  Black African 1% 54% 66% Other/missing 10% 17% 15% UK born 72% 23% 18% Non-UK born, fluent English 25% 59% 65% Non-UK born, not fluent English 3% Time on ART (years) 8.3 (4.0,13.8) 7.1 (3.5, 11.4) 7.2 (3.6,11.1) CD4 570 (430,750) 472 (328,682) 570 (397,757) Non-adherence 31% 34% 40% 0.004 Self-reported number of times ≥ 2 consecutive days or ART missed in 2 months prior to questionnaire or 1 or more missed ART dose in past 2 weeks *chi squared test

Baseline characteristics: MSM, MSW, women On ART started > 6 months ago N=2445 N (%/ median IQR) MSM N=1678 MSW N=285 Women N=482 p-value* Age <40 years 28% 20% 38% <0.001 White 89% 29% 19% <0.001  Black African 1% 54% 66% Other/missing 10% 17% 15% UK born 72% 23% 18% Non-UK born, fluent English 25% 59% 65% Non-UK born, not fluent English 3% Time on ART (years) 8.3 (4.0,13.8) 7.1 (3.5, 11.4) 7.2 (3.6,11.1) CD4 570 (430,750) 472 (328,682) 570 (397,757) Non-adherence 31% 34% 40% 0.004 Self-reported number of times ≥ 2 consecutive days or ART missed in 2 months prior to questionnaire or 1 or more missed ART dose in past 2 weeks *chi squared test

Baseline characteristics: MSM, MSW, women On ART started > 6 months ago N=2445 MSM N=1678 MSW N=285 Women N=482 *p-value Enough money for basic needs 53% 27% 21% <0.001  Mostly enough money 24% 25% Sometimes enough money 12% 31% 29% Never enough money 8% 18% Currently employed 58% 44% <0.001 Homeowner 22% 16% Renting 50% 60% 67% Unstable/ Other 6% 17% University 39% 34% High supportive network# 59% 55% 0.263 Medium support 33% 32%   Low support 10% 9% 13% Living with partner 42% Partner, not living together 14% 20% 23% No Partner 45% Depression★ (PHQ-9) 0.004 Temporary accommodation, staying with family or friends, homeless, other; #Modified Duke Functional Social Support Questionnaire (FSSQ); ★ Major/Other depression by PHQ-9. *chi squared test

Baseline characteristics: MSM, MSW, women On ART started > 6 months ago N=2445 MSM N=1678 MSW N=285 Women N=482 *p-value Enough money for basic needs 53% 27% 21% <0.001  Mostly enough money 24% 25% Sometimes enough money 12% 31% 29% Never enough money 8% 18% Currently employed 58% 44% <0.001 Homeowner 22% 16% Renting 50% 60% 67% Unstable/ Other 6% 17% University 39% 34% High supportive network# 59% 55% 0.263 Medium support 33% 32%   Low support 10% 9% 13% Living with partner 42% Partner, not living together 14% 20% 23% No Partner 45% Depression★ (PHQ-9) 0.004 Temporary accommodation, staying with family or friends, homeless, other; #Modified Duke Functional Social Support Questionnaire (FSSQ); ★ Major/Other depression by PHQ-9. *chi squared test

Baseline characteristics: MSM, MSW, women On ART started > 6 months ago N=2445 MSM N=1678 MSW N=285 Women N=482 *p-value Enough money for basic needs 53% 27% 21% <0.001  Mostly enough money 24% 25% Sometimes enough money 12% 31% 29% Never enough money 8% 18% Currently employed 58% 44% <0.001 Homeowner 22% 16% Renting 50% 60% 67% Unstable/ Other 6% 17% University 39% 34% High supportive network# 59% 55% 0.263 Medium support 33% 32%   Low support 10% 9% 13% Living with partner 42% Partner, not living together 14% 20% 23% No Partner 45% Depression★ (PHQ-9) 0.004 Temporary accommodation, staying with family or friends, homeless, other; #Modified Duke Functional Social Support Questionnaire (FSSQ); ★ Major/Other depression by PHQ-9. *chi squared test

Cross sectional analysis: on ART > 6 months and factors associated with VL> 50 c/ml p=0.003♯ p<0.001 % with VL>50 copies/ml ♯ Chi squared tests

Cross sectional analysis: on ART 6 months: socioeconomic factors associated with VL> 50 p<0.001♯ p<0.001 p=0.005 p=0.15 p=0.046 % with VL>50 copies/ml ♯p values by Chi squared tests

Prevalence ratios from modified Poisson regression Cross sectional analysis: comparing VL>50 c/ml in MSM to MSW and women Women MSW MSM p=0.008 p=0.013 p=0.045 p=0.24 p=0.007 p=0.17 p=0.023 p=0.23 Unadjusted Adjusted for age and UK birth/ English fluency Adjusted age and financial hardship Adjusted for age and employment Adjusted for age and housing status Adjusted for age and education Adjusted for age, socioeconomic factors, partner, supportive network and depression Adjusted for age only 0.1 1.0 2.0 Prevalence ratios from modified Poisson regression

Longitudinal analysis: VL rebound (first VL >200c/mL) during follow-up N=1586 with VL<50c/mL on ART, started ≥6 months ago# Women N=271 MSW N=163 MSM N=1152 Number with VL>200c/mL during follow-up 24 19 43 Person-years at risk 406 241 1929 Rebound rate* /100 p-y [95% CI] 5.9 [3.7, 8.8] 7.9 [4.8, 12.3] 2.2 [1.6, 3.0] p<0.001 for comparison across gender/sexuality groups * First VL>200c/mL after questionnaire date. Mean (range) follow-up from questionnaire 20 months (range 0.1 to 37 months) #Includes only participants with linked clinic follow-up VL data

Hazard ratios by Cox PH regression Longitudinal analysis: comparing first VL>200 c/ml in MSM to MSW and women p<0.001 p=0.008 Hazard ratios by Cox PH regression

Conclusions and Recommendations In the ASTRA study, MSW and women compared to MSM more likely to have: -detectable viral load -viral load rebound after suppression Differences in virological outcomes between MSM and women are largely explained by socio-economic circumstances They appear to have less impact for virological differences between MSM and MSW Interventions aiming at assisting those at socioeconomic disadvantage may improve viral load outcomes in women and to some extent MSW Researchers should encourage equity of access and participation Clinical research should include measures of socioeconomic factors

Acknowledgments Thank you to all ASTRA study participants ASTRA clinic teams Royal Free Hospital: Alison Rodger; Margaret Johnson; Jeff McDonnell; AdebiyiAderonke Mortimer Market Centre: Richard Gilson; Simon Edwards; Lewis Haddow; Simon Gilson; Christina Broussard; Robert Pralat; SonaliWayal Brighton and Sussex University Hospital: Martin Fisher; Nicky Perry; Alex Pollard; Serge Fedele; Louise Kerr; Lisa Heald; Wendy Hadley; Kerry Hobbs; Julia Williams; ElaneyYoussef; Celia Richardson; Sean Groth North Manchester General Hospital: Ed Wilkins; Yvonne Clowes; Jennifer Cullie; Cynthia Murphy; Christina Martin; Valerie George; Andrew Thompson HomertonUniversity Hospital: Jane Anderson; SifisoMguni; DamilolaAwosika; Rosalind Scourse East Sussex Sexual Health Clinic: KazeemAderogba; Caron Osborne; Sue Cross; Jacqueline Whinney; Martin Jones Newham University Hospital: Rebecca O’Connell; Cheryl Tawana Whipps Cross University Hospital: Monica Lascar; ZandileMaseko; Gemma Townsend; Vera Theodore; Jas Sagoo ASTRA core team: Fiona Lampe; Alison Rodger; Andrew Speakman; Andrew Phillips ASTRA data management: Andrew Speakman; Marina Daskalopoulou; Fiona Lampe ASTRA advisory group: Lorraine Sherr; Simon Collins; Jonathan Elford; Alec Miners; Anne Johnson; Graham Hart; Anna-Maria Geretti; Bill Burman CAPRA grant Advisory Board: Nick Partridge; Kay Orton; Anthony Nardone; Ann Sullivan The ASTRA study presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research funding scheme (RP-PG-0608-10142). The views expressed in this presentation are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health