Tenofovir disoproxil fumarate in pregnancy and prevention of mother-to-child transmission of HIV-1: is it time to move on from zidovudine?
OBJECTIVE
Zidovudine (ZDV) has been the cornerstone of antiretroviral (ARV) therapy for pregnant women infected with HIV-1 in the prevention of mother-to-child transmission (MTCT) and remains the only licensed ARV for use in pregnancy. We explored the current and future roles of tenofovir disoproxil fumarate (TDF) in the prevention of MTCT of HIV-1.


METHODS
We reviewed the published literature by conducting database searches of in vitro, animal and clinical studies, reported in journals and at conferences, using the search terms Tenofovir/gs4331/viread, pregnant/pregnancy, lactate, lactation, natal, reproduce/reproduction, placenta/placental, malformation, and teratogenicity/teratogenic.


RESULTS
In a macaque model, perinatal exposure to very high dose tenofovir resulted in bone toxicity in some offspring. However, perinatal use of TDF, both single dose and as part of highly active antiretroviral therapy in women, has been well tolerated in the short term by mothers and their infants. Further, the addition of single-dose TDF to single-dose nevirapine (SD-NVP) during delivery following maternal ZDV use during pregnancy significantly reduces the frequency of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance.


CONCLUSIONS
The addition of TDF to SD-NVP reduces NNRTI resistance. The role of TDF in this setting and during pregnancy for reducing rates of MTCT requires investigation. While short-term toxicity data are encouraging, long-term follow-up of exposed mothers and infants is required.
Foster
C
C
The Family Clinic, Imperial College NHS Trust, St Mary's Campus, London W2 1NY, UK. drcarolinefoster@btinternet.com
Lyall
H
H
Olmscheid
B
B
Pearce
G
G
Zhang
S
S
Gibb
D M
DM
D000225:Adenine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D000818:Animals; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D001847:Bone Diseases / Q000139:chemically induced; D002648:Child; D002675:Child, Preschool; D000013:Congenital Abnormalities / Q000453:epidemiology / Q000209:etiology; D004195:Disease Models, Animal; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000635:transmission*; D015497:HIV-1; D006297:Health Services Accessibility; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008251:Macaca; D008928:Mitochondria / Q000187:drug effects; D019829:Nevirapine / Q000627:therapeutic use; D063065:Organophosphonates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000453:epidemiology; D000068698:Tenofovir; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
D019380:Anti-HIV Agents; D063065:Organophosphonates; D015215:Zidovudine; D019829:Nevirapine; D000068698:Tenofovir; D000225:Adenine