zidovudine
Sources réglementaires consultées
Indications approuvées
- Traitement antirétroviral combiné du VIH et prévention de la transmission materno-fœtale selon le protocole.
Contre-indications
Absolues
- Hypersensibilité ; neutrophiles <0,75 × 10^9/l’ou hémoglobine <7,5 g/dl.
- Chez le nouveau-ne : hyperbilirubinemie necessitant un traitement autre que la phototherapie ou transaminases >5 fois la limite superieure de la normale.
Mises en garde cliniques
- Elle peut provoquer anémie sévère, neutropénie et myélosuppression ; surveiller la numération et adapter ou arrêter. — CIMA/AEMPS, ficha técnica 57486
- Elle peut provoquer myopathie, acidose lactique et hépatomégalie sévère avec stéatose ; arrêter en cas de suspicion. — CIMA/AEMPS, ficha técnica 57486
Interactions médicamenteuses
- SévèreGanciclovir, interféron, ribavirine ou autres myélosuppresseurs
Mécanisme: La toxicité hématologique peut être additive.
Recommandation: Surveiller la numération et éviter ou adapter l’association.
CIMA/AEMPS, ficha técnica 57486
- ModéréeAutres médicaments contenant de la zidovudine
Mécanisme: Ils doublent l’exposition.
Recommandation: Ne pas dupliquer la zidovudine.
CIMA/AEMPS, ficha técnica 57486
- SévèreRifampicine
Mécanisme: Elle réduit l’AUC de la zidovudine et peut entraîner une perte d’efficacité.
Recommandation: Éviter l’association.
CIMA/AEMPS, ficha técnica 57486
- SévèreStavudine
Mécanisme: Un antagonisme antiviral existe in vitro.
Recommandation: Éviter l’association.
CIMA/AEMPS, ficha técnica 57486
Effets indésirables
Communs (≥1%)
Anémie, neutropénie, céphalées, nausées et malaise
Rares mais graves
Aplasie médullaire, acidose lactique, hépatomégalie avec stéatose et myopathie
Grossesse et allaitement
Elle peut être utilisée pendant la grossesse dans le schéma indiqué pour traiter le VIH ou prévenir la transmission verticale. La notice déconseille l’allaitement chez les personnes vivant avec le VIH traitées.
Bibliographie récente (PubMed)
In 1989, one in four (25%) infants born to women living with HIV were infected; by the age of 2 years, there was 25% mortality among them due to HIV. These and other pieces of data prompted the development of interventions to offset vertical transmission, including the landmark Pediatric AIDS Clinical Trial Group Study (PACTG 076) in 1994. This study reported a 67.5% reduction in perinatal HIV transmission with prophylactic antenatal, intrapartum, and postnatal zidovudine. Numerous studies since then have provided compelling evidence to further optimize interventions, such that annual transmission rates of 0% are now reported by many health departments in the US and elimination has been validated in several countries around the world. Despite this success, the elimination of HIV's vertical transmission on the global scale remains a work in progress, limited by socioeconomic factors such as the prohibitive cost of antiretrovirals. Here, we review some of the key trials underpinning the development of guidelines in the US as well as globally, and discuss the evidence through a historic lens. Zidovudine has been well studied during breastfeeding. Milk levels are low and most breastfed infants do not have detectable blood levels. Some breastfed infants have developed anemia during maternal therapy. Achieving and maintaining viral suppression with antiretroviral therapy decreases breastfeeding transmission risk to less than 1%, but not zero. Individuals with HIV who are on antiretroviral therapy with a sustained undetectable viral load and who choose to breastfeed should be supported in this decision. If a viral load is not suppressed, banked pasteurized donor milk or formula is recommended.[1,2] Extended postnatal prophylaxis of breastfed infants with zidovudine should continue until breastfeeding is stopped.[3] The antivirals are a large and diverse group of agents that are typically classified by the virus infections for which they are used, their chemical structure a
In the REPRIEVE trial of statin therapy in people with HIV, pitavastatin reduced major adverse cardiovascular events (MACE) among those with low-to-moderate risk of cardiovascular disease (CVD). We aimed to investigate associations between former and current use of antiretroviral therapy (ART) on entry into the REPRIEVE trial and the development of MACE. This longitudinal cohort analysis was a prespecified secondary analysis of the REPRIEVE trial, a double-blind, placebo-controlled, multicentre, phase 3 randomised trial conducted at 137 sites in 12 countries. REPRIEVE enrolled people with HIV aged 40-75 years, currently on ART, with a CD4 count of more than 100 cells per μL and low-to-moderate CVD risk, and randomly assigned them to receive pitavastatin or placebo. For this secondary analysis, participants' history of ART use, including lifetime exposure to selected agents, was collected at baseline. The primary outcome of interest was time-to-first MACE. Stratified Cox proportional hazards models were used to estimate the relative hazards of MACE associated with ART exposures. Effects of no previous exposure, former exposure, and current exposure to ART at entry to the study were compared using models unadjusted and adjusted for entry risk factors and ART regimen at entry. All analyses were conducted in the intention-to-treat population. The REPRIEVE trial is registered at ClinicalTrials.gov, NCT02344290, and is complete. Between March 26, 2015, and July 31, 2019, 7769 participants were enrolled into the REPRIEVE trial. 2419 (31·1%) of 7769 participants were assigned female at birth and 5350 (68·9%) were assigned male at birth. 3208 (41·3%) of 7769 participants were Black or African American, 2704 (34·8%) were White, 1138 (14·6%) were Asian, and 719 (9·3%) were of other races. Participants had a median age of 50·0 years (IQR 45·0-55·0), LDL cholesterol concentration of 106 mg/dL (86-128), 10-year atherosclerotic cardiovascular disease risk score of 4·5% (2·1-7·0),
HIV treatment has evolved since the introduction of antiretroviral therapy (ART) in the 1990s. Earlier treatment strategies, and the introduction of integrase inhibitors in preferred first-line ART have fundamentally changed cardiovascular side effects due to HIV infection and ART. This review provides an update on cardiovascular toxicity of contemporary ART. Cardiovascular disease (CVD) risk, including heart failure, is still increased in people living with HIV (PLWH). Exposure to older antiretrovirals, including stavudine and zidovudine, still impact on CVD risk through persistent changes in body fat distribution years after discontinuation. Protease inhibitors (PI) and efavirenz have associated metabolic disturbances and increased risk of CVD, although use is decreasing worldwide. Integrase inhibitors and CCR5 antagonists seem to have negligible immediate CVD toxicity. Weight gain on newer antiretrovirals including integrase inhibitors is a reason for concern. CVD risk should be monitored carefully in PLWH who were exposed to first generation ART, efavirenz or to PIs. Registries should capture ART use and CVD events to stay informed on actual clinical risk in the current era of rapid initiation on integrase inhibitor-based ART.