DMPA and HIV Acquisition Risk

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?

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

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)

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

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

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

“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

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

Randomized Trial of 7800 women South Africa, Zambia, Swaziland, Kenya DMPA vs Copper IUD vs Implants

Scheduled to begin this Summer

Echo Trial

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

The SQ Formulation of Depo-Provera Is Efficacious at Lower

Concentrations

4.0

3.0

2.0

1.0

0

50 100 150 200 0

Depo-Provera (n=8) SQ Formulation of Depo-Provera (n=42)

Time (days)

MPA

Ser

um

Con

cent

ratio

n (n

g/m

L)

Data on file.

LD = lower dose.

Couples Need Better Access to Wider Variety of Methods Especially LARCs

Thank you

Studies Comparing DMPA and Net-En for HIV Acquisition Risk