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. METHODOLOGY: 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. DISCUSSION: 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.

Lymphocyte transformation in lepromatous leprosy: a study of the influence of disease activity and symptom duration

The lymphocyte hyporesponsiveness to M. leprae of patients with active lepromatous leprosy has been well described. This immune defect is less well understood in terms of its time of origin, possible reversibility and specificity. To further examine the persistence and specificity of this abnormality, lymphocyte transformation tests of 93 leprosy patients to lepromin, BCG and PHA were studied. Among lepromatous patients, a decreased response to M. leprae was seen, whether the disease was active or inactive. Decreased responses to BCG were found in lepromatous patients with active disease, but not in those with inactive disease. The duration of patient symptoms was not associated with differences in LTT responses among the active lepromatous patients.