1. University of North Carolina
Modelling combination interventions to prevent HIV among girls of school age in South Africa
HPTN 068
Marie Stoner, PhD
University of North Carolina
Chapel Hill, NC, USA
23 July, 2019

2. Introduction
Combination prevention strategies may be an effective way to prevent HIV in adolescent girls and young women (AGYW)
Example: combining a cash transfer with adolescent friendly health services
Resource intensive
Modelling strategies are a cost-effective way to determine what might work before implementation

3. Factors associated with incident HIV infection in the HPTN 068 cohort
Depression
Intimate Partner Violence (IPV)
Age-disparate relationships
Transactional Sex
Low school attendance
2,533 AGYW years in rural South Africa

4. Goal
Identify combination interventions by modeling the effects of known population interventions among AGYW on these five HIV-associated risk factors
Depression
IPV
Age-disparate relationships
Transactional sex
Low school attendance

5. The G-Formula
Create a simulated cohort (N=50,000) based on observed distribution of key characteristics
Ask more nuanced questions that are relevant for policy and planning
Conventionally studies compare:
Risk of HIV in girls who are depressed versus in those who are not depressed
Using G-formula:
If we intervened to reduce depression by 25%, how much would this reduce HIV incidence?

6. Estimating the effects of interventions
Percent of risk factor observed in data
Entirely exposed vs. entirely unexposed (standard comparison)
C. Observed vs. no one exposed
D. Observed vs reduced by X%
Westreich 2017, Epidemiology

7. Objectives
Estimate population intervention effects on HIV acquisition in AGYW
Quantify the potential reduction in HIV incidence after intervening on a combination of the 5 HIV-associated risk factors

8. Effective interventions to reduce HIV-associated risk factors
36.2% reduction in depression (Chibanda et al. 2016)
3.9% reduction low school attendance (Baird et al 2010)
10% reduction in IPV (Pettifor et al. 2016)
3% reduction in transactional sex (3%) (Cluver et.al 2013)
1.5% reduction in age-disparate partnership (Dupas et. al. 2011)

9. Age-disparate Partnership
Entirely exposed vs. entirely unexposed (standard comparison)
Low School Attendance 
Depression
Ever IPV
Age-disparate Partnership
Transactional Sex
Risk Difference (%)
-8.5
(-8.8, -8,1)
-3.2
(-3.5, -2.9)
-0.3
(-0.7,0.0)
-2.6
(-2.9, -2.2)
-6.6
(-6.9, -6.2)
Risk Ratio
0.41
(0.39,0.43)
0.64
(0.61,0.67)
0.95
(0.9,1)
0.70
(0.67,0.74)
0.46
(0.44,0.48)
Bold p<0.005

10. Age-disparate Partnership
Observed vs. no one exposed
Low School Attendance 
Depression
Ever IPV
Age-disparate Partnership
Transactional Sex
Prevalence
6.8%
18.1%
16.9%
7.8%
9.3%
Risk Difference (%)
-0.5
(-0.7, -0.2)
-0.6
(-0.9,-0.3)
-0.2
(-0.5,0.1)
-0.7
(-1.0, -0.4)
Risk Ratio
0.93
(0.88,0.97)
0.64
(0.61,0.67)
0.97
(0.93,1.02)
(0.92,1.02)
0.89
(0.84,0.94)
Bold p<0.005

11. Observed vs reduced by X%
Intervention 1: school attendance alone (3.9% reduction)
Intervention 2: depression alone (36.2% reduction)
Intervention 3: transactional sex alone (3% reduction)

12. Combination intervention effects
Intervention 4: school attendance, depression and transactional sex
Intervention 5: school attendance and depression
Intervention 6: school attendance and transactional sex
Intervention 7: transactional sex and depression

13. Conclusions and next steps
Intervening on depression alone will reduce risk of HIV infection in AGYW
Transactional sex, depression and low school attendance had the largest population effects
We need stronger interventions to substantially reduce these risk factors
G-formula is a useful tool to determine how combination interventions will reduce HIV incidence across populations

14. Acknowledgements UNC Audrey Pettifor Amanda Selin Linda Kimaru
Aimee Julien
Mary Jane Hill
Stephanie DeLong
Jess Edwards
Carolyn Halpern
Allison Aiello
Bill Miller
Pettifor Advisee Group
National Institutes of Health (NIH) [R01MH and R01 MH110186] )
Carolina Population Center [P2C HD050924].
South Africa
Kathleen Kahn
Xavier Gomez-Olive
Catherine MacPhail (WrHI/UOW)
Ryan Wagner
Stephen Tollman
Rhian Twine
Audrey Khosa
HTPN 068 study team and participants
HPTN Laboratory Center
Susan Eshleman
Oliver Laeyendecker
Yaw Agyei
HIV Prevention Trials Network

15. The HIV Prevention Trials Network is funded by the National Institute of Allergy and Infectious Diseases (UM1AI068619, UM1AI068613, UM1AI ), with co-funding from the National Institute of Mental Health, and the National Institute on Drug Abuse, all components of the U.S. National Institutes of Health. The work presented here was funded by NIH grants UM1AI068619, UM1AI and UM1AI
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Leadership and Operations Center (LOC):
Grant #: UM1AI068619
Laboratory (LC):
Grant #: UM1AI
Statistical and Data Management Center (SDMC):
Grant #: UM1AI
Please remove any award number not applicable to presented research

16. References
Cluver L, Boyes M, Orkin M, Pantelic M, Molwena T, Sherr L. Child-focused state cash transfers and adolescent risk of HIV infection in South Africa: A propensity-score-matched case-control study. Lancet Glob Heal 2013; 1. doi: /S X(13)
Chibanda D, Weiss HA, Verhey R, Simms V, Munjoma R, Rusakaniko S, et al. Effect of a primary care-based psychological intervention on symptoms of common mental disorders in Zimbabwe: A randomized clinical trial. JAMA - J Am Med Assoc Published Online First: doi: /jama
Baird S, Chirwa E, McIntosh C, Ozler B. The short-term impacts of a schooling conditional cash transfer program on the sexual behavior of young women. Health Econ 2010; 19 Suppl:55–68.
Dupas P. Do teenagers respond to HIV risk information? Evidence from a field experiment in Kenya. Am Econ J Appl Econ Published Online First: doi: /app.3.1.1
Pettifor A, MacPhail C, Hughes JP, Selin A, Wang J, Gómez-Olivé FX, et al. The effect of a conditional cash transfer on HIV incidence in young women in rural South Africa (HPTN 068): a phase 3, randomised controlled trial. Lancet Glob Heal Published Online First: doi: /S X(16)
Westreich D, Edwards JK, Rogawski ET, Hudgens MG, Stuart EA, Cole SR. Causal Impact: Epidemiological Approaches for a Public Health of Consequence. Am J Public Health Published Online First: doi: /ajph