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Human immunodeficiency virus (HIV)
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Richard Basilan, William Salzer
A 6-week course of zidovudine chemoprophylaxis is recommended for all HIV-exposed neonates in the United States, ideally initiated within 6 to 12 hours of delivery. It may be appropriate to shorten the course to 4 weeks in situations where concerns exist regarding adherence or toxicity, as the optimal duration for neonatal chemoprophylaxis is not known. In other countries, such as the United Kingdom and Ireland, a 4-week course is the recommended regimen, while WHO guidelines indicate a 4- to 6-week course of zidovudine to be appropriate. Please see Table 3 for specific dosing for zidovudine.
Infections
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
The first Phase III study (PACTG 076) demonstrating the efficacy of zidovu-dine in the prevention of HIV transmission from mother to fetus was published in 1994 [3]. The trial enrolled 477 women infected with HIV. The transmission rate was 8% in the group treated with zidovudine and 25% in the group given placebo. The dosing schedule used in this study was 100 mg zidovudine orally, 5 times daily, administered until delivery, followed by a 2 mg/kg per-partum intravenous infusion and the administration of 2 mg/kg 4 times daily orally to the newborn from birth until age 6 weeks. This dosing schedule was based on the fact that the plasma half-life of zidovudine is very short (~1 hour) [4]. When the protocol was designed, it was thought that having a short interval between doses would ensure that the molecule was continuously present in the plasma. Later, after publication of the results the recommended dosing schedule for adults was changed to 300 mg BD, based on intracellular pharmacokinetic studies [5] that showed that the intracellular half-life of the phosphorylated metabolites was much longer than the half-life of zidovudine in plasma. Thus, in subsequent studies[6] on the transmission of HIV from mother to fetus, zidovudine 300 mg BD was given to the mother as recommended for the curative treatment of adults. However, the dosing schedule recommended for neonates was not modified, and it remains 2 mg/kg QDS.
Zidovudine
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Catherine L. Cherry, Suzanne M. Crowe
Zidovudine is indicated for the treatment and prevention of HIV infection, generally given in combination with other antiretroviral agents. It is now less commonly used in Australia, Europe, and the USA, although patients exist in these areas who have been taking zidovudine as part of their combination therapy with virologic suppression and no clinical evidence of toxicity for 20 years. Zidovudine remains indicated for use as first-line antiretroviral therapy in low- and middle-income countries (WHO, 2013).
Pharmacological approaches to prevent vertical transmission of HIV and HBV
Published in Expert Review of Clinical Pharmacology, 2022
Emanuela Zappulo, Agnese Giaccone, Nicola Schiano Moriello, Ivan Gentile
Intravenous (IV) zidovudine readily crosses the placenta providing a pre-exposure prophylaxis to the infant during labor. IV ZDV is indicated in patients with HIV RNA >1000 copies/ml or unknown viral load within 4 weeks of delivery. It is also recommended in patients with documented ZDV resistance who did not receive ZDV as part of the ARV regimen during pregnancy. Its benefit in those with HIV RNA >1000 copies/ml remains controversial, and the US guidelines do not recommend IV ZDV in patients with HIV RNA <50 copies/ml near delivery who are adherent to their ARV regimen [61]. The British guidelines also recommend that untreated women presenting in labor at term should also be given a start dose of nevirapine 200 mg as it rapidly crosses the placenta achieve effective concentrations in the neonate for up to 10 days, then start oral zidovudine and lamivudine 150 mg bd plus raltegravir 400 mg bd [68].
HIV TB coinfection - perspectives from India
Published in Expert Review of Respiratory Medicine, 2021
Bharat Bhushan Rewari, Amitabh Kumar, Partha Pratim Mandal, Anoop Kumar Puri
Zidovudine was the first drug shown to be effective against HIV in 1985 but the virus developed resistance quickly with single drug. By 1995, many studies demonstrated the benefit of using a two-drug combination in preventing progression of disease and reduction in mortality as well-opportunistic infections. The year 1996 was a turning point in the treatment options when results of using a triple drug combination using new very potent agents, protease inhibitors, became available. But these were associated with issue of multiple pills, high costs, and toxicity issues. Discovery of non-nucleoside reverse transcriptase inhibitors (Nevirapine and later Efavirenz) made the therapy simpler and soon became standard of care along with two nucleoside reverse transcriptase inhibitors. The availability of different drugs in fixed dose combination (FDC) by Indian pharmaceutical companies in generic forms made therapy simpler, reduced the number of tablets to be taken daily thereby increasing adherence potential. The offer of ART at ‘a dollar a day’ by an Indian pharmaceutical company was clearly the game changer in increasing access to antiretroviral (ARV) drugs globally. The annual cost of treatment has come down significantly from USD$ 10,000 in late nineties to around USD$ 60 presently.
The Changing Global Epidemic of HIV and Ocular Disease
Published in Ocular Immunology and Inflammation, 2020
Remco P. H. Peters, Philippe G. Kestelyn, Manfred Zierhut, John H. Kempen
The clinical face of the HIV epidemic has changed dramatically over the past three decades. In the early 1980s people were dying of a clinical syndrome labeled the Acquired Immune Deficiency Syndrome (AIDS) for which there was no treatment; Pneumocystis carinii (now Pneumocystis jirovecii) pneumonia, cytomegalovirus (CMV) retinitis, and Kaposi sarcoma were the most common presenting opportunistic infections at that time. In 1985, HIV was discovered; the first antiretroviral drug, zidovudine, was registered in 1987, the first nucleoside reverse transcriptase inhibitor (NRTI). The effect of monotherapy with zidovudine on morbidity and mortality was favorable but limited due to rapid emergency of resistance.6 The same was observed for monotherapy with other drugs from the same class of NRTIs such as didanosine and stavudine.7 Introduction of triple therapy consisting of a dual NRTI backbone combined with a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor changed the prognosis of HIV dramatically, as the probability of resistance-inducing mutations was dramatically reduced with triple (or more) drug therapy. This approach (HAART), introduced in 1995–1996, has become the mainstay of HIV treatment; a wide array of therapeutic options is now available.7 Widespread use of HAART, now including new classes of drugs with fewer side-effects and a higher genetic barrier to resistance, have resulted in a near-normal life expectancy of HIV-infected individuals on suppressive HAART.8