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.

Adult↗

PubMed2002

Hyperlactataemia and lactic acidosis during antiretroviral therapy: relevance, reproducibility and possible risk factors.

OBJECTIVE: To evaluate the prevalence, outcome and possible risk factors for hyperlactataemia and lactic acidosis in HIV-positive persons receiving antiretroviral therapy. METHODS: Cross-sectional and longitudinal data from a prospectively collected clinical database. Associations with antiretroviral regimen, clinical and laboratory parameters were assessed using univariate and multivariate Cox's proportional hazards model. RESULTS: Patients naive to therapy and patients on current therapy for a minimum of 4 months were assessed. Median lactate was 1.1 mol/l in 253 untreated individuals and 1.4 mmol/l in 1239 patients stable on therapy for at least 4 months. At least two on-therapy samples were available for 750 of the 1239 individuals, taken a median 92 days apart. Lactate measurement showed a low positive predictive value of 38.9% but a high negative predictive value (98%) for normal values. Lactate was elevated > or = 2.4 mmol/l in 102 individuals on at least one occasion. In the multivariate Cox's proportional hazards model, no demographic characteristics were associated with hyperlactataemia. Didanosine-containing regimens doubled the relative hazard of hyperlactataemia compared with those sparing didanosine. Abacavir-containing regimens reduced the hazard of hyperlactataemia. Choice of thymidine analogue did not influence risk. Hyperlactataemia was associated with acid-base disturbance. Use of didanosine and female sex were over-represented amongst nine patients with severe hyperlactataemia (> 5 mmol/l) or lactic acidosis. CONCLUSIONS: Screening of lactate is of limited use in asymptomatic individuals on antiretroviral therapy. Raised lactate represents part of a spectrum of lactate and acid-base disturbance that infrequently includes lactic acidosis. Didanosine appears associated with an increased risk of hyperlactataemia.

Acidosis, Lactic↗

PubMed2002

Switching to zidovudine plus lamivudine plus abacavir maintains viral suppression in patients with high viral load before antiretroviral therapy: a retrospective clinical cohort analysis.

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Anti-HIV Agents↗

PubMedDate not supplied

Considerations in selecting protease inhibitor therapy.

Over the past 10 years, highly active antiretroviral therapy that included a protease inhibitor has played a significant role in reducing morbidity and mortality among HIV-infected individuals. The early protease inhibitors were associated, however, with some significant limitations that posed major obstacles to their use--limited potency, difficult side effects, high regimen complexity and potential for cross-resistance. Important advances in the protease inhibitor class, including ritonavir boosting and the approval of two new protease inhibitors with the potential for once daily dosing, have led to simpler, better-tolerated protease-inhibitor therapy with the potential for improved efficacy, less toxicity and a reduced risk of the development of HIV resistance. Protease inhibitor characteristics and patient preferences should be considered in selecting the protease inhibitor that maximizes the opportunity for long-term efficacy and tolerability of highly active antiretroviral therapy.

Drug Administration Schedule↗