Visiting Researcher, University of the Witwatersrand Sex, risk and preferences: Multipurpose HIV prevention products in South Africa Matthew Quaife Research Fellow in Health Economics, London School of Hygiene and Tropical Medicine Visiting Researcher, University of the Witwatersrand STRIVE Learning Lab 30th November 2017 Collaborators and co-authors: Fern Terris-Prestholt, Robyn Eakle, Maria Cabrera, Sinead Delany-Moretlwe, Peter Vickerman

Background and motivation South Africa has one of the largest and high profile generalised HIV epidemics in the world Estimated 12% prevalence and increasing

Background and motivation South Africa has one of the largest and high profile generalised HIV epidemics in the world Estimated 12% prevalence and increasing Predominantly heterosexual epidemic – has some nuances: Women 1.4x more like to be HIV positive than men Adolescent girls 8x more likely to be HIV positive than boys of the same age HIV prevalence for female sex workers (FSWs) in South Africa estimated at 70% (in Johannesburg)

Background and motivation South Africa has one of the largest and high profile generalised HIV epidemics in the world Estimated 12% prevalence and increasing Predominantly heterosexual epidemic – has some nuances: Women 1.4x more like to be HIV positive than men Adolescent girls 8x more likely to be HIV positive than boys of the same age HIV prevalence for female sex workers (FSWs) in South Africa estimated at 70% (in Johannesburg) For years, condoms were the only efficacious “product” to prevent HIV transmission Many reasons why condoms have not been effective at preventing a large epidemic E.g. gender norms, power asymmetry, transactional sex, incentives for risk in sex work

Background and motivation New antiretroviral (ARV)-based HIV prevention methods on the brink of roll-out. Five products in development – different ways of delivering ARV drugs Potential to increase agency of vulnerable groups – no partner participation required

Background and motivation New antiretroviral (ARV)-based HIV prevention methods on the brink of roll-out. Five products in development – different ways of delivering ARV drugs Potential to increase agency of vulnerable groups – no partner participation required But: Only oral PrEP and intravaginal ring have been proven efficacious Single purpose – only protect against HIV (for the moment) Concerns of substitution from condom use Efficacy ≠ effectiveness => adherence issues

Background and motivation: Models

Background and motivation: Models “13% of current HIV funding was found not to support priority interventions[…] [This] should be de-prioritised, with funding reallocated to more evidence-based approaches.” South African National Strategic Plan for HIV and TB: 2017-2022. NDoH 2016.

Methods: Discrete Choice Experiment (DCE)

Methods: Discrete Choice Experiment (DCE)

Methods: Data Collection

Methods: Data Collection Adult Females Adult Males Adolescent Females Female sex workers Total 203 recruited 202 recruited 204 recruited 203 recruited 812 recruited 35 self-reported HIV positive (17%) 16 self-reported HIV positive (8%) 5 self-reported HIV positive (2%) 81 self-reported HIV positive (40%) 137 self-reported HIV positive (17%) 10 not sexually active 4 not sexually active 126 not sexually active 0 not sexually active 140 not sexually active 158 completed DCE 182 completed DCE 73 completed DCE 122 completed DCE 535 completed DCE

Results: Product Preferences

Results: Product Preferences

Impact: Rollout scenarios    Product(s) HIV protection Pregnancy protection Scenario 1  Oral PrEP X Scenario 2 Intravaginal ring Scenario 3 Scenario 4 Injectable ARV Microbicide Gel SILCS diaphragm & microbicide gel Scenario 5 Diaphragm & microbicide gel 1. Current practice 2 & 3: Next few years 4. Kitchen sink 5. Multipurpose kitchen sink

Uptake Predictions

Impact: Model Simple static transmission model using South African demographic and HIV epidemiological data For each product (𝑥), protection is a function of efficacy ( 𝐸 𝑥 ) and use ( 𝑈 𝑥 ) 𝑃 𝑥 = 𝐸 𝑥 𝑈 𝑥

Impact: Model Simple static transmission model using South African demographic and HIV epidemiological data For each product (𝑥), protection is a function of efficacy ( 𝐸 𝑥 ) and use ( 𝑈 𝑥 ) Then: 𝑃 𝑥 = 𝐸 𝑥 𝑈 𝑥 Overall protection = additional protection from new products – condom migration + existing condom protection 𝑃 𝑛 = 𝑈 𝑥 1− 1−𝜀 𝑖=1..𝑛 𝑈𝑐 𝑖 𝐸 𝑥 + 1−𝜀 𝑖=1..𝑛 𝐸 𝑖 𝑈𝑐 𝑖 +𝜀 𝑖=1..𝑛 1− 𝐸 𝑥 𝐸 𝑖 𝑈𝑐 𝑖 + 1− 𝑈 𝑥 𝑖=1..𝑛 𝐸 𝑖 𝑈𝑛𝑐 𝑖 𝑖=1..𝑛 𝐸 𝑖 𝑈𝑛𝑐 𝑖 (1−𝜀) = propensity to still use condoms, Uc and Unc = product use among condom/non-condom users, Ei = efficacy

Impact: DALYs averted Estimate benefits from one year of product introduction No consideration of staged uptake over time, adherence DALYs averted through preventing HIV infections Do not consider benefits from unintended pregnancies averted Averaged DALYs averted per infection estimated for each population Estimate model with low/medium/high HIV incidence for each group No age-weighting Discount rate 3% (all costs and benefits) Willingness-to-pay threshold of $1,175 (Woods et al. 2016)

Cost model Fixed costs National start-up costs Training of providers Mass media   MPT research and development Variable costs Facility distribution costs Staff time Product Health system mark-up and overheads Averted health costs ART treatment Planned and unplanned miscarriage and births

Cost-effectiveness

But PrEP is already here… Women 16-24 Women 25-49 FSW Incidence assumption Low Central High Single-purpose Adding vaginal ring to PrEP (Scenario 2 compared to Scenario 1) $1,691 $801 $30 $4,763 $3,282 $1,008 $792 $-66 $-398 Multi-purpose Adding MPT ring to PrEP (Scenario 3 compared to Scenario 1) $727 $243 $-225 $-401 $-482 $-669 $-532 $-709 $-791 Adding MPT range to single-purpose range (Scenario 5 compared to Scenario 4) $1,214 $543 $-79 $88 $-114 $-503 $-1,810 $-1,502 $-1,334 *Negative ICER values in this table indicate cost-saving interventions with a positive impact

Conclusions MPTs likely cost-effective among younger women (16-24) and FSWs The most cost-effective scenarios were those with MPT products Likely cost-effective to add a MPT ring to PrEP provision, other scenarios more nuanced Estimates very sensitive to incidence Overall impact likely to be low Full scenario predicts 19% incidence reduction among younger women, 8% among older women and FSWs UNAIDS 90-90-90 targets estimated to lead to 48% reduction in incidence

Acknowledgements All study participants Interviewers and staff of Progressus Research and Development Bill and Melinda Gates Foundation Economic and Social Research Council

Thank you for listening @matthew_quaife matthew.quaife@lshtm.ac.uk

Additional slides

Uptake Predictions DCEs tell us how much people value different attributes - E.g. Pregnancy protection is twice as important as STI protection Cardinal estimates of utility provided by attributes Adult Females Adolescent Girls FSW HIV protection (full) 2.33 (0.53)*** 2.59 (0.88)*** 2.19 (0.425)*** Pregnancy prevention 0.16 (0.05)*** 0.48 (0.09)*** 0.14 (0.044)*** STI protection 0.22 (0.06)*** 0.44 (0.1)*** 0.36 (0.048)***

Contraceptive protection (varied) Uptake Predictions DCEs tell us how much people value different attributes E.g. Pregnancy protection is twice as important as STI protection We know the likely attributes of new products. E.g.: Product HIV efficacy STI efficacy Contraceptive protection (varied) Frequency of use Oral PrEP 61 N N (Y) Daily Vaginal Ring 55 Weekly

Contraceptive protection (varied) Uptake Predictions DCEs tell us how much people value different attributes E.g. Pregnancy protection is twice as important as STI protection We know the likely attributes of new products. E.g.: Because we know how much people value each attribute, we can predict the probability that somebody will choose oral PrEP over a vaginal ring Product HIV efficacy STI efficacy Contraceptive protection (varied) Frequency of use Oral PrEP 61 N N (Y) Daily Vaginal Ring 55 Weekly 𝑃𝑟𝑜𝑏𝑎𝑏𝑖𝑙𝑖𝑡𝑦 𝑜𝑟𝑎𝑙 𝑃𝑟𝐸𝑃 = 𝑢𝑡𝑖𝑙𝑖𝑡 𝑦 𝑜𝑟𝑎𝑙 𝑃𝑟𝐸𝑃 𝑢𝑡𝑖𝑙𝑖𝑡 𝑦 𝑜𝑟𝑎𝑙 𝑃𝑟𝐸𝑃 +𝑢𝑡𝑖𝑙𝑖𝑡 𝑦 𝑣𝑎𝑔𝑖𝑛𝑎𝑙 𝑟𝑖𝑛𝑔

The economics of sex work

Hypothesis Price premium of unprotected sex Supply1: Baseline Supply2: After intervention A Price decrease B Demand: remains constant Quantity increase Quantity of unprotected Sex

Methods: The Choice Experiment

Methods: Framing Introduction and survey questions First CE task (no framing) “You have the choice between providing services to one of two clients. Which would you prefer?”

Methods: Framing Introduction and survey questions First CE task (no framing) Introduction to PrEP

Methods: Framing HIV –ves only Introduction and survey questions First CE task (no framing) Introduction to PrEP Second CE task (with framing) “Now I would like you to choose between 10 more sets of clients, but this time I would like you to make your choices imagining you were using a product which prevented you from getting infected with HIV. This means that there would be no risk of getting HIV from any client, whether or not you use a condom.”

MNL Results (1) Unframed MNL Coeff. SE Price (ZAR 100) 0.16 *** 0.56 Condom 8.04 0.32 Anal sex -4.99 0.24 Think client has HIV -0.78 0.19 Think client has STI -1.38 0.21 Opt-out 2.90 0.215 Interaction terms PrEP framing x price PrEP framing x condom use PrEP framing x anal sex PrEP framing x client HIV PrEP framing x client STI PrEP framing x opt-out Log likelihood -1083 Implied condom differential ZAR 4,903 Reduction of 73% *p<0.1, **p<0.05, ***p<0.01

MNL Results (1) (2) Unframed MNL PrEP framed MNL Coeff. SE Price (ZAR 100) 0.16 *** 0.56 0.24 0.05 Condom 8.04 0.32 6.56 0.29 Anal sex -4.99 -5.01 0.23 Think client has HIV -0.78 0.19 -0.46 0.18 Think client has STI -1.38 0.21 -1.09 Opt-out 2.90 0.215 1.83 Interaction terms PrEP framing x price PrEP framing x condom use PrEP framing x anal sex PrEP framing x client HIV PrEP framing x client STI PrEP framing x opt-out Log likelihood -1083 -1273 Implied condom differential ZAR 4,903 ZAR 2,733 Reduction of 73% *p<0.1, **p<0.05, ***p<0.01

MNL Results (1) (2) (3) Unframed MNL PrEP framed MNL Interacted MNL Coeff. SE Price (ZAR 100) 0.16 *** 0.56 0.24 0.05 0.14 0.48 Condom 8.04 0.32 6.56 0.29 7.53 0.26 Anal sex -4.99 -5.01 0.23 -4.95 0.22 Think client has HIV -0.78 0.19 -0.46 0.18 0.87 0.17 Think client has STI -1.38 0.21 -1.09 -1.31 Opt-out 2.90 0.215 1.83 2.58 0.15 Interaction terms PrEP framing x price 0.12 ** PrEP framing x condom use -0.40 PrEP framing x anal sex -0.17 PrEP framing x client HIV 0.50 0.10 PrEP framing x client STI 0.92 PrEP framing x opt-out -0.48 0.11 Log likelihood -1083 -1273 -2386 Implied condom differential ZAR 4,903 ZAR 2,733 Reduction of 73% *p<0.1, **p<0.05, ***p<0.01