Viral Load Is Key Factor in Mother-to-Child HIV Transmission

		SUMMARY: 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.

By Liz Highleyman

Study 1

In 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 (non-transmitters).

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).

Results

	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.
	HIV-transmitting mothers were less like than non-transmitters to be receiving ART at the time of conception (16% vs 45%; P = 0.017).
	Women who transmitted HIV were more likely to report problems with treatment adherence compared with non-transmitters (37% vs 12%; P = 0.005).
	Transmitting women had a significantly higher maximum viral load than non-transmitting mothers (P < 0.001).
	At week 30 of gestation, transmitting mothers were more likely than non-transmitters to have viral load > 100,000 copies/mL (42% vs 11%).
	Women who transmitted HIV were less likely than non-transmitters to have viral load < 500 copies/mL at all time points:
	14 weeks: 0% of transmitters vs 38.1% of non-transmitters (P = 0.02); 28 weeks: 7.7% vs 62.1%, respectively (P = 0.005); 32 weeks: 21.4% vs 71.1%, respectively (P = 0.004).
	Viral load differences remained significant when restricting the analysis to the 10 cases of intrapartum transmission.
	In 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).
	However, 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.

Study 2

In 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.

This 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.

Results

	Overall, 32% of the women in the cohort had detectable HIV RNA at the time of delivery.
	Among 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).
	Among 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).
	Among 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.
	However, type of ART regimen was not a significant predictor of detectable HIV RNA at delivery in either the treatment-experienced or treatment-naive groups.

"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.

2/16/10

References

R 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.

IT 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.