Safer Conception Strategies for HIV-Serodiscordant Couples: How Safe Is Safe Enough?
JID
Safer Conception Strategies for HIV-Serodiscordant Couples: How Safe Is Safe Enough?
Andrea L. Ciaranello 1 2
Lynn T. Matthews 0 2
0 Center for Global Health, Massachusetts General Hospital , Boston
1 Medical Practice Evaluation Center
2 Division of Infectious Disease, Department of Medicine
EDITORIAL COMMENTARY
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With access to antiretroviral therapy
(ART), human immunodeficiency virus
(HIV)–infected men and women are
living longer and healthier lives and have
childbearing desires similar to those of
HIV-unaffected individuals [1]. Many
are in HIV-serodiscordant sexual
partnerships (with an HIV-uninfected
partner), and attempts at conception confer
sexual HIV transmission risk [2]. HIV
risk reduction strategies are available for
HIV-serodiscordant couples, in which the
male is infected, who want to conceive
(Table 1), but there are limited data to
inform which or how many concurrent
methods a couple should adopt. ART for
the HIV-infected male partner is
recommended regardless of conception plans,
to reduce HIV transmission risk to
partners and improve the man’s own health
[11, 12]. Because adherence to ART is
imperfect and genital shedding of HIV may
occur even in the presence of suppressed
plasma viral load, couples may seek
additional methods to reduce transmission
risk. For an uninfected woman wishing
to conceive with an infected male partner
who is receiving ART, oral preexposure
prophylaxis (PrEP) may be a valuable
option, particularly if use of ART or ART
adherence by the male partner is limited.
Combining PrEP for the female partner
(oral tenofovir/emtricitabine, or TDF/
FTC) – with ART administration to the
male partner for safer conception has
been acceptable in observational studies
[13–15]. Because PrEP trials were
conducted without receipt of ART by the
infected partner and ART trials were
conducted without receipt of PrEP by
the uninfected partner, there are no direct
clinical data to estimate the benefit of
using PrEP and ART together to decrease
periconception HIV transmission risk,
compared with either intervention alone.
In this issue of The Journal of
Infectious Diseases, Hoffman et al use a
thoughtfully designed simulation model
to investigate the role of PrEP, ART, or
both in male-infected, HIV-serodiscordant
couples who are attempting to conceive.
When clinical data are limited,
simulation models can help to inform
decision-making. If multiple studies provide
partial information, a single model can
integrate available data. When data are
equivocal or missing, investigators make
explicit assumptions about which values
to use in a model and then vary these
values in sensitivity analyses to identify
the thresholds at which decisions would
change; this allows readers to understand
whether more data are needed to
accurately inform clinical choices [16].
Here, Hoffman et al combine
transmission risks from separate PrEP trials,
ART-as-prevention trials, and
observational studies of age-stratified pregnancy
rates, and conduct extensive sensitivity
analyses on key model parameters. They
focus this analysis on couples who
maintain the high rates of ART-mediated viral
suppression and PrEP adherence seen in
the HPTN 052 and Partners PrEP trials
[3 ,5, 17, 18]. They also assume that
both partners are aware of each others’
HIV status, have been screened and
treated for sexually transmitted infections
(STIs), and have completed normal
fertility evaluations. There are 3 primary
messages from their analysis.
First, if couples limit condomless sex to
the 2 days before and the day of
ovulation, and if the male partner is receiving
virally suppressive ART, PrEP for the
female partner provides little additional
benefit. The authors define a “successful”
outcome as one in which the female
partner remains uninfected and a full-term
pregnancy occurs. With ART alone, the
yearly chance of this successful outcome is
29.1%; with ART plus PrEP, this chance
is 29.2%, which is essentially equivalent
within the margin of error of the model
results.
Second, if couples choose a single
intervention, ART for the male partner is
projected to be more effective in reducing
transmission than PrEP for the female
Sex without condoms
limited to peak fertility
ART for the infected
partner
PrEP (oral, daily FTC/TDF)
for the uninfected
partner [5, 6]
STI treatment [7, 8]
Sperm processing [9, 10]
Estimated Risk
Reduction, %
Unknown Reduces cumulative HIV exposure
while permitting conception
96% in clinical trial [3]; Reduces morbidity and mortality for
approximately 64% in infected partner while reducing risk
non-trial setting [4] of transmission to uninfected
partner
63–75 Female controlled
Reduces morbidity for the treated
individuals and may reduce risk of
HIV acquisition and transmission
Highly effective
Difficult for couples to determine time of peak
fertility and/or negotiate condomless sex
Detectable HIV may remain in semen despite
suppressed plasma virus
Treatment refusal and sub-optimal adherence
ar (...truncated)