Safety and efficacy of saquinavir soft-gelatin capsules + zidovudine + optional lamivudine in pregnancy and prevention of vertical HIV transmission.
BACKGROUND
The treatment of HIV infection during pregnancy significantly and substantially reduces the risk of mother-to-child transmission. Although triple therapy is the standard of care for management of HIV infection in adults, the safety of many approved antiretroviral agents in pregnancy is not currently established.


METHODS
An open-label pilot study conducted in Thailand and the UK of the safety of saquinavir soft-gel capsules 1200 mg three times daily administered in the second and third trimester of pregnancy in combination with local standard-of-care antiretroviral therapy. Infants received local standard-of-care antiretroviral therapy after delivery. Steady-state pharmacokinetics were performed in a subset of mothers at 4 weeks after the commencement of saquinavir therapy and paired samples collected from the mother and infant cord blood at delivery.


RESULTS
Eighteen antiretroviral-naive pregnant women with a mean viral load of 4.2 log10 and CD4 cell count of 481/mm(3) were recruited. All patients received zidovudine and 3 (all in the UK) received lamivudine. There were no serious adverse events and no discontinuations due to adverse events. Viral load declined by 1.6 log10 at week 4 and was less than 400 copies/mL at delivery in 16/17 mothers. Sixteen live births were recorded, with two in utero deaths-one secondary to an accident and the second due to antiphospholipid syndrome. Both deaths were considered by investigators to be unrelated to study therapy. All infants were HIV negative at subsequent follow-up and no fetal abnormalities were observed. Pharmacokinetic data suggested that mothers had relatively low exposures to saquinavir despite an excellent virologic response. Saquinavir was not detected in cord blood.


CONCLUSIONS
Saquinavir soft-gel capsules are well tolerated during pregnancy and are not associated in this small study with birth abnormalities. Transmission of HIV infection from mother to child was successfully prevented in all cases. Low maternal exposures of saquinavir were noted. However, these did not appear to affect virologic efficacy of the combination. Samples from cord blood indicate minimal fetal exposure to saquinavir.
Departments of Microbiology and Infectious Diseases, Chiang Mai University Hospital, Chiang Mai, Thailand.
Vicharn
V
Vithayasai
Graeme J
GJ
Moyle
Volaluck
V
Supajatura
Nisit
N
Wattanatchariya
Siripon
S
Kanshana
Preecha
P
Sirichthaporn
Krai
K
Dabtham
Pichaya
P
Somburanasin
Tawachai
T
Chantawuttinan
Andrew M
AM
Hill
David
D
Hawkins
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000635:transmission; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000378:metabolism; D012449:Safety; D019258:Saquinavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013785:Thailand; D006113:United Kingdom; D014766:Viremia / Q000150:complications / Q000188:drug therapy; D015215:Zidovudine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D019380:Anti-HIV Agents; D019259:Lamivudine; D015215:Zidovudine; D019258:Saquinavir