Reduction of Maternal-Infant Transmission of Human Immunodeficiency Virus Type 1 with Zidovudine Treatment

Connor, Edward; Sperling, Rhoda; Gelber, Richard D.; Kiselev, P.N.; Scott, Gwendolyn B.; OʼSullivan, Mary J.; Vandyke, Russell; Bey, Mohammed; Shearer, William T.; Jacobson, Robert L.; Jiménez, Eleanor; O'Neill, Edward H.; Bazin, Brigitte; Delfraissy, Jean François; Culnane, Mary; Coombs, Robert W.; Elkins, Mary; Moye, John; Stratton, Pamela; Balsley, James

doi:10.1056/nejm199411033311801

Cited by 3,383 publications

(1,167 citation statements)

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“…The effectiveness of highly active antiretroviral treatment (HAART) regimens in reducing mother‐to‐child vertical transmission (MTCT) of HIV‐infection and in delaying disease progression has been demonstrated and should therefore be offered to all pregnancies 1, 2, 3. Anti‐retroviral (ARV) treatment comprised of two nucleoside reverse transcriptase inhibitors (NRTIs) and non‐nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) is recommended in pregnancy by the United States, World Health Organization and European guidelines 4, 5.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial toxicity and caspase activation in HIV pregnant women

Hernández

Morén

Catalán-García

et al. 2016

J Cellular Molecular Medi

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To assess the impact of HIV‐infection and highly active anti‐retroviral treatment in mitochondria and apoptotic activation of caspases during pregnancy and their association with adverse perinatal outcome. Changes of mitochondrial parameters and apoptotic caspase activation in maternal peripheral blood mononuclear cells were compared at first trimester of pregnancy and delivery in 27 HIV‐infected and ‐treated pregnant women versus 24 uninfected pregnant controls. We correlated immunovirological, therapeutic and perinatal outcome with experimental findings: mitochondrial DNA (mtDNA) content, mitochondrial protein synthesis, mitochondrial function and apoptotic caspase activation. The HIV pregnancies showed increased adverse perinatal outcome (OR: 4.81 [1.14–20.16]; P < 0.05) and decreased mtDNA content (42.66 ± 5.94%, P < 0.01) compared to controls, even higher in naïve participants. This depletion caused a correlated decrease in mitochondrial protein synthesis (12.82 ± 5.73%, P < 0.01) and function (20.50 ± 10.14%, P < 0.001), not observed in controls. Along pregnancy, apoptotic caspase‐3 activation increased 63.64 ± 45.45% in controls (P < 0.001) and 100.00 ± 47.37% in HIV‐pregnancies (P < 0.001), in correlation with longer exposure to nucleoside analogues. HIV‐infected women showed increased obstetric problems and declined genetic and functional mitochondrial parameters during pregnancy, especially those firstly exposed to anti‐retrovirals. The apoptotic activation of caspases along pregnancy is emphasized in HIV pregnancies promoted by nucleoside analogues. However, we could not demonstrate direct mitochondrial or apoptotic implication in adverse obstetric outcome probably because of the reduced sample size.

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Section: Introductionmentioning

confidence: 99%

Mitochondrial toxicity and caspase activation in HIV pregnant women

Hernández

Morén

Catalán-García

et al. 2016

J Cellular Molecular Medi

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“…Of currently available antiretrovirals, zidovudine is the agent for which there is the most information; information about other antiretrovirals is limited. In the PACTG 076 study the only significant side effect among ZDV recipients was the presence of anemia in ZDV-exposed infants; however, the anemia was mild and resolved spontaneously without any need for transfusion (64). There has been no evidence of an increase in congenital abnormalities in infants who were exposed in utero to ZDV; uninfected children who were participants in this study have now been studied for over 4 years with no evidence of an impact of ZDV on growth, neurodevelopment, or immunologic status (65).…”

Section: Antiretroviral Therapy: Known and Unknown Risksmentioning

confidence: 99%

Human immunodeficiency virus and assisted reproduction: reconsidering evidence, reframing ethics

Lyerly

Anderson

2001

Fertility and Sterility

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“…12,13 Moreover, strong scientific evidence supporting the use of ART in the prevention of mother-to-child transmission in both developed and developing country settings has added further argument to the biological plausibility of such therapy in other exposure settings. 14,15 In this context, the US Centers for Disease Control and Prevention (CDC) have stated that: ''because the therapy remains unproven and can pose risks, physicians should consider its use only in individual circumstances when the probability of HIV infection is high, the therapy can be initiated promptly, and adherence to the regimen is likely. It should not be used routinely and should never be considered a form of primary prevention.…”

mentioning

confidence: 99%