Dr. Jim Shelton of USAID discusses the long-acting reversible hormonal contraceptive DMPA (depot medroxyprogesterone acetate) and addresses concerns about whether or not it increases the risk of HIV acquisition.

1. DMPA and HIV Acquisition
Risk

2.  Some, but not all, observational studies have
suggested an increase in the risk of HIV
acquisition for women using DMPA.
 What should we make of those data?

3.  Results based on comparing risk in women using
HC vs those using other methods and
sometimes not using
 Likely/Possible differences between HC and
Non-HC (and among HC):
 Condom use in comparison population
 Coital frequency
 Perceived “reliability” both for clients and providers
e.g. Injectables vs OC
Serious Problem of Confounding in Observational
Studies of Hormonal Contraception and HIV
Acquisition

4.  Most studies are secondary analyses of clinical trials designed for other
purposes (e.g. ARVs as HIV prevention). Data collection on
contraception secondary.
 Analyses attempt to control for various variables but are limited by the
underlying data.
 Data on condom use, highly suspect including “social/investigator”
bias – responses to facilitate staying in the trial and “getting out the
door”
 Data on coital frequency typically also highly suspect
 Difference between people actually condoms using for contraception
(typically very large part of the control groups) vs other use
 In Heffron study
 Only < 10% reported any unprotected sex in the last month.
 But pregnancy rate in non-hormonal users was 16%.
Confounding Issue
(Continued)

5.  Data from 18 studies
 Recrunched the individual-level data
 Methodologically sophisticated in many ways
 But limitations on addressing condom use, since
most studies collected very limited data (e.g.
yes/no at various points in time) and subject to
concerns about validity particularly in HIV
prevention trials.
Morrison 2015 Meta-Analysis

6.  Overall hazard ratio – 1.5 ( 1.24 - 1.83)
 Best studies hazard ratio – 1.22 (0.99 – 1.50)
 Oral Contraceptives not associated with
increased risk
Morrison 2015 Results for DMPA

7.  Follow up of 1393 discordant couples in Zambia
 Investigators have close relationship with
subject population and excellent follow-up
 252 infections
 Hazard Ratios:
 OCs – 1.3 ( 0.9-1.8)
 Implants – 1.1 (0.5-2.2)
 DMPA – 1.2 (0.8-1.7)
Wall et al, 2015

8. “Unless the true effect size approaches a relative
risk of 2.19, it is unlikely that reductions in IHC
(injectable hormonal contraception) could result in
public health benefit, with the possible exception
of those countries in southern Africa with the
largest HIV epidemics”
- Butler et al, AIDS, 2013
Modeling Competing Risk with
Maternal Mortality

9. WHO extensively reviewed the
evidence on HC and HIV acquisition
in 2014.
Use of DMPA by women at risk of
HIV remains Category 1 – No
Restriction

10.  Randomized Trial of 7800 women
 South Africa, Zambia, Swaziland, Kenya
 DMPA vs Copper IUD vs Implants
 Scheduled to begin this Summer
Echo Trial

11. New formulation of Depo-Provera:
Depo-subQ Provera 104, for delivery with Uniject
Depo-subQ Provera 104:
t New formulation for subQ injection
t 30% lower dose (104 mg vs. 150 mg)
t Rapid onset of action
t Same effectiveness, same length of protection
(>3 months)
t Approved by USFDA (2005) and EMA/UK
Uniject:
t Single dose, single package
t Prefilled, sterile, non-reusable
t Short needles for subQ injection (easier use by
non-clinical personnel/CHWs)
t Compact; easy to use and store
t Potential for home- and self-injection
t Approval by EMA and LDC registration
forthcoming
t PK study completed for injection in arm;
Acceptability studies to begin in early 2012;
Available for roll-out in late 2012-2013

12. The SQ Formulation of Depo-
Provera Is Efficacious at Lower
Concentrations
4.0
3.0
2.0
1.0
0
50 100 150 2000
Depo-Provera (n=8)
SQ Formulation of
Depo-Provera (n=42)
Time (days)
MPASerum
Concentration(ng/mL)
Data on file.
LD = lower dose.

13. Couples Need Better Access to Wider Variety of
Methods Especially LARCs

14. Thank you

15. Studies Comparing DMPA and Net-En for HIV Acquisition Risk