By
Liz Highleyman
While
studies have shown that zidovudine
(AZT; Retrovir) is safe and effective for preventing mother-to-child
HIV transmission, newer antiretroviral
drugs have not been as extensively studied. Rather than using single agents,
treatment guidelines in wealthy
countries recommend that HIV positive pregnant women should receive a fully suppressive
combination antiretroviral therapy
(ART) regimen.
Zidovudine
has fallen out of favor for non-pregnant HIV patients due to toxicities. Tenofovir
is a generally well-tolerated and widely recommended nucleoside/nucleotide
reverse transcriptase inhibitor (NRTI) component of ART that may be suitable
for use during pregnancy.
Kathleen
Squires and colleagues looked at data submitted to the APR, an international prospective
registry established in 1989 that collects voluntary reports from healthcare providers
and is designed to detect teratogenic effects (congenital anomalies or birth defects)
associated with antiretroviral drug exposure during pregnancy. Because most exposures
-- especially in developed countries -- involve multiple antiretroviral agents,
the investigators also evaluated congenital anomalies associated with selected
commonly used regimens.
Through
July 31, 2008, a total of 11,950 prospective instances of pregnancy in HIV positive
women taking antiretroviral drugs were reported to the registry. Among these,
1146 cases involved use of tenofovir (FDA-approved in 2001). Some cases were still
under investigation and others were lost to follow-up, so the final analysis included
10,471 pregnancies, of which 1056 involved tenofovir exposure. Out of these 10,471
pregnancies, 9948 resulted in live births.
The
median age of the women enrolled in the registry was about 28 years overall, and
30 years for those who used tenofovir. Among tenofovir recipients, 64% were black,
17% were Hispanic, and 12% were white. About 20% had advanced immune deficiency
with a CD4 count below 200 cells/mm3.
Results
 | The
overall prevalence of congenital anomalies in live-born infants with any antiretroviral
drug exposure was 2.7% (272 out of 9948 live births). |
| For
exposure during the first trimester -- the most sensitive period for fetal development
-- the prevalence was 2.9% (126 out of 4329 live births). |
| For
exposure during the second or third trimester, the prevalence was 2.6% (145 out
of 5618 live births). |
| These
rates are comparable to those for infants born to HIV negative mothers, according
to the Centers for Disease Control and Prevention (CDC) population-based birth
defects surveillance system (2.7% among live births during 1989-2003). |
| The
prevalence of congenital anomalies among infants with first trimester exposure
to any tenofovir-containing regimen was 2.3% (14 of 606 live births). |
| Among
infants with second or third trimester exposure to tenofovir, the prevalence was
1.5% (5 of 336 live births). |
| None
of the 5 infants born to HIV monoinfected (i.e., without viral hepatitis) women
using tenofovir plus emtricitabine
(Emtriva) plus efavirenz (Sustiva)
-- the 3 drugs in the Atripla coformulation -- had congenital anomalies, although
efavirenz is considered contraindicated due to birth defects observed in animal
studies and in humans. |
| Among
infants exposed to tenofovir plus emtricitabine (the 2 drugs in the Truvada coformulation)
plus any third drug other than efavirenz, the congenital anomaly prevalence was
2.2% (7 out of 321 live births). |
| Among
infants born to women taking any other tenofovir-containing regimen, the rate
was 1.4% (8 out of 556 live births). |
| In
addition, no anomalies were reported among women exposed to tenofovir during pregnancy
who had spontaneous abortions (miscarriages), induced abortions, or stillbirths.
|
Based
on these findings, the investigators concluded, "no increase in prevalence
of congenital anomalies was seen through prospective voluntary reporting to the
APR with use of [tenofovir]-containing antiretroviral regimens during pregnancy."Prevalence
of births defects among women exposed to antiretroviral drugs during the first
trimester was similar to the prevalence during the second or third trimester,
they added, and "no specific patterns of birth defects were observed."
Thomas
Jefferson Univ., Philadelphia, PA; Gilead Sci., Inc., Foster City, CA.
9/15/09
Reference
K
Squires, B Olmscheid, and S Zhang. Tenofovir-DF
(TDF)-Containing Antiretroviral (ARV) Regimens for Treatment of HIV in Pregnancy:
Findings from the Antiretroviral Pregnancy Registry (APR). 49th Interscience
Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009). San Francisco.
September 12-15, 2009. Abstract H-917.
