Load Is Key Factor in Mother-to-Child HIV Transmission
HIV viral load, both throughout pregnancy and at the
time of delivery, plays a key role in whether an HIV
positive woman will transmit the virus to her baby
during gestation or birth, according to 2 recently published
studies. While antiretroviral
therapy (ART) has dramatically lowered the rate
of perinatal HIV transmission, these findings indicate
there is still room for further risk reduction, even
in developed countries.
the first study, published in the February
15, 2010 issue of Clinical Infectious Diseases, Roland
Tubiana from Hôpital Pitié Salpêtrière
in Paris and colleagues aimed to identify factors associated with
residual perinatal HIV transmission in a low-risk setting.
The rate of mother-to-child HIV
transmission is as low as 0.5%-1.0% among HIV positive women
who deliver at full term, are receiving ART and have a plasma
viral load < 500 copies/mL at the time of delivery, and do
not breast-feed their infants, the study authors noted as background.
However, this situation accounted for 20% of the HIV-infected
children born during 1997-2006 in the French Perinatal Cohort.
The investigators performed a case-control study nested within
the larger French Perinatal Cohort study. The analysis included
19 case patients (women who transmitted HIV) and 60 control women
All infants were full-term (at least 37 weeks gestation) and none
of the mothers breastfed their babies. Infants were considered
to have been infected during gestation if they had detectable
HIV DNA at the time of birth; if not, infection was assumed to
have occurred during delivery (intrapartum).
Women who transmitted HIV and non-transmitters did not differ
according to geographical origin, baby's gestational age at
the time of mother's HIV diagnosis, type of ART received,
or elective Cesarean delivery.
mothers were less like than non-transmitters to be receiving
ART at the time of conception (16% vs 45%; P = 0.017).
who transmitted HIV were more likely to report problems with
treatment adherence compared with non-transmitters (37% vs
12%; P = 0.005).
women had a significantly higher maximum viral load than non-transmitting
mothers (P < 0.001).
week 30 of gestation, transmitting mothers were more likely
than non-transmitters to have viral load > 100,000 copies/mL
(42% vs 11%).
who transmitted HIV were less likely than non-transmitters
to have viral load < 500 copies/mL at all time points:
weeks: 0% of transmitters vs 38.1% of non-transmitters
(P = 0.02);
weeks: 7.7% vs 62.1%, respectively (P = 0.005);
weeks: 21.4% vs 71.1%, respectively (P = 0.004).
load differences remained significant when restricting the
analysis to the 10 cases of intrapartum transmission.
a multivariate analysis at 30 weeks adjusted for viral load,
CD4 cell count, and time at ART initiation, viral load was
the only factor independently associated with mother-to-child
transmission (adjusted odds ratio 23.2; P < 0.001).
0.4% of women with viral load consistently below 50 copies/mL
still transmitted HIV to their babies.
Based on these results, the researchers concluded, "Early
and sustained control of viral load is associated with a decreasing
residual risk of mother-to-child transmission of HIV-1."
Guidelines should take into account not only CD4 count and risk
of pre-term delivery, but also baseline HIV viral load for determining
when to start ART during pregnancy, they recommended, adding that
maternal viral load should be controlled well before delivery.
They also suggested that transmission during delivery might be
due to HIV shedding in the genital tract, offering another potential
opportunity for prevention.
the second study, described in the January
8, 2010 advance online edition of the Journal of Acquired Immune
Deficiency Syndromes, Ingrid Katz from Brigham and Women's
Hospital in Boston and colleagues evaluated factors -- including
specific ART regimen -- associated with detectable viral load
at the time of delivery.
analysis included 630 HIV positive women enrolled in the Women
and Infants Transmission Study (WITS) between 1998 and 2005 who
received combination ART during pregnancy.
32% of the women in the cohort had detectable HIV RNA at the
time of delivery.
the subset of 364 ART-experienced women, lower CD4 cell count
and higher HIV viral load at study enrollment were significantly
associated with detectable HIV (> 400 copies/mL) at delivery
(adjusted odds ratio [OR] 1.20 per 100 cells/mm3 and 1.52
per log copies/mL, respectively).
the 266 ART-naive women, both lower CD4 count and higher HIV
RNA at enrollment were again linked to detectable viral load
at delivery (adjusted OR 1.24 per 100 cells/mm3 and 1.35 per
log copies/mL, respectively).
treatment-naive women, maternal age at the time of delivery
(adjusted AOR 0.92 per 10 years older) and mother's illegal
drug use (adjusted OR 3.15) were also significantly associated
with detectable viral load at delivery.
type of ART regimen was not a significant predictor of detectable
HIV RNA at delivery in either the treatment-experienced or
"Lack of viral suppression at delivery was common in the
WITS cohort, but differences by antiretroviral regimen were not
identified," the study authors concluded. "Despite a
transmission rate below 1% in the last 5 years of the WITS cohort,
improved measures to maximize HIV-1 RNA suppression at term among
high-risk women are warranted."
Study 1: Département des Maladies Infectieuses et Tropicales,
Assistance Publique des Hôpitaux de Paris (AP?HP), Hôpital
Pitié Salpêtrière; Institut National de la
Santé et de la Recherche Médicale (INSERM) U943;
Institut National Etudes Démographiques; Laboratoire de
Virologie, AP?HP, Hopital Necker; Université Paris Descartes;
Université Paris 7, Paris Diderot; Service de Santé
Publique et Épidémiologie, AP?HP, Hopital Bicêtre;
Service d'Hématologie et d'Oncologie Pédiatrique;
Hôpital Trousseau; Service de Pédiatrie Générale,
AP?HP, Hôpital Robert Debré; Unité d'Immunologie
Hématologie Pédiatrique, AP?HP, Hôpital Necker,
Paris, France; Faculté de Médecine Paris?Sud, Université
Paris?Sud, Le Kremlin?Bicêtre; Service de Gynécologie?Obstétrique,
AP?HP, Hôpital Louis Mourier, Colombes, France.
Study 2: Brigham and Women's Hospital, Boston, MA; Beth Israel
Deaconess Medical Center, Boston, MA; Harvard Medical School,
Boston, MA; Clinical Trials and Surveys Corporation, Baltimore,
MD; Eunice Kennedy Shriver National Institute of Child Health
and Human Development, National Institutes of Health, Bethesda,
MD; Harvard School of Public Health, Boston, MA.
Tubiana, J Le Chenadec, C Rouzioux, and others. Factors Associated
with Mother-to-Child Transmission of HIV-1 Despite a Maternal
Viral Load < 500 Copies/mL at Delivery: A Case-Control Study
Nested in the French Perinatal Cohort (EPF-ANRS CO1). Clinical
Infectious Diseases 50(4): 585-596 (Abstract).
February 15, 2010.
Katz, R Shapiro, D Li, and others. Risk Factors for Detectable
HIV-1 RNA at Delivery Among Women Receiving Highly Active Antiretroviral
Therapy in the Women and Infants Transmission Study. Journal
of Acquired Immune Deficiency Syndromes (Abstract).
January 8, 2010.