Henrin A: A New Anti-HIV Ent-Kaurane Diterpene from Pteris henryi.

Henrin A (1), a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and was further confirmed by X-ray crystallographic analysis. The compound was evaluated for its biological activities against a panel of cancer cell lines, dental bacterial biofilm formation, and HIV. It displayed anti-HIV potential with an IC50 value of 9.1 µM (SI = 12.2).

A review of the toxicity of HIV medications.

Antiretroviral therapy has changed human immunodeficiency virus (HIV) infection from a near-certainly fatal illness to one that can be managed chronically. More patients are taking antiretroviral drugs (ARVs) for longer periods of time, which naturally results in more observed toxicity. Overdose with ARVs is not commonly reported. The most serious overdose outcomes have been reported in neonates who were inadvertently administered supratherapeutic doses of HIV prophylaxis medications. Typical ARV regimens include a "backbone" of two nucleoside reverse transcriptase inhibitors (NRTI) and a "base" of either a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor. New classes of drugs called entry inhibitors and integrase inhibitors have also emerged. Older NRTIs were associated with mitochondrial toxicity, but this is less common in the newer drugs, emtricitabine, lamivudine, and tenofovir. Mitochondrial toxicity results from NRTI inhibition of a mitochondrial DNA polymerase. Mitochondrial toxicity manifests as myopathy, neuropathy, hepatic failure, and lactic acidosis. Routine lactate assessment in asymptomatic patients is not indicated. Lactate concentration should be obtained in patients taking NRTIs who have fatigue, nausea, vomiting, or vague abdominal pain. Mitochondrial toxicity can be fatal and is treated by supportive care and discontinuing NRTIs. Metabolic cofactors like thiamine, carnitine, and riboflavin may be helpful in managing mitochondrial toxicity. Lipodystrophy describes changes in fat distribution and lipid metabolism that have been attributed to both PIs and NRTIs. Lipodystrophy consists of loss of fat around the face (lipoatrophy), increase in truncal fat, and hypertriglyceridemia. There is no specific treatment of lipodystrophy. Clinicians should be able to recognize effects of chronic toxicity of ARVs, especially mitochondrial toxicity.

Management of persons infected with human immunodeficiency virus requiring admission to the intensive care unit.

Rates of admission to the intensive care unit (ICU) for persons infected with human immunodeficiency virus (HIV) remain relatively unchanged in the modern era despite advances in antiretroviral therapy (ART) and improvements in ICU survival. Critical care may be required for patients with HIV because of severe opportunistic infections or malignancy, antiretroviral drug toxicity, or critical illness seemingly unrelated to HIV, and each of these scenarios may present different management challenges. In this article, the epidemiology of HIV-related ICU admission is reviewed and key management issues are discussed.

Overdose with HAART: are we managing these patients adequately?

Increasing numbers of HIV/AIDS-infected individuals have presented to medical casualty at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) after attempting suicide by overdosing on their antiretroviral therapy. Since 2009, medical gastro-enterology at CMJAH has been the primary specialty unit for cases of accidental or intentional overdose. Psychiatry and other medical sub-specialties are consulted as needed. Our unit sees approximately 1 case a month of accidental/intentional overdose with antiretrovirals. Between January and September 2010, 6% of all overdoses seen at CMJAH were of antiretroviral origin. Supportive care is provided and patients undergo psychiatric evaluation. The information available on overdoses with antiretrovirals is from studies in developed countries, where intravenous drug users and men who have sex with men make up the bulk of the HIV-positive population. This differs significantly from South Africa, which now has the largest antiretroviral programme in the world. With little evidence related to this type of overdose, are we approaching the management, monitoring and follow-up of these patients correctly?

Zidovudine (AZT) overdose in a healthy newborn receiving postnatal prophylaxis.

CONTEXT: Pediatric medication dosing and administration, faced with inherent challenges of dose to body weight adjustment and variable delivery vehicles, may lead to inadvertent errors effectively resulting in overdose. Zidovudine (AZT), a nucleoside analog reverse transcriptase inhibitor (NRTI), is a commonly prescribed medication to treat HIV-exposed newborns, with limited overdose data in this patient population. Metabolic acidosis with elevated lactate is the most serious consequence of AZT toxicity in the adult population, associated with mortality. Other significant effects may include neutropenia and hepatic dysfunction. CASE REPORT: A 4-day-old male infant who received two inadvertent 10-fold overdoses of AZT while being treated for HIV postnatal prophylaxis. The newborn developed a transient metabolic acidosis with elevated lactate that resolved within 24 h, a small increase in AST, and persistent neutropenia for 5 weeks. The patient's mother cited several key factors leading to the dosing error. DISCUSSION: The paucity of AZT overdose data in newborns and infants compels this case report, which reviews the published literature and provides insight into prevention and improvement of pediatric patient safety.

Uncomplicated outcome after an accidental overdose of nevirapine in a newborn.

We report the first case of a massive accidental overdose of nevirapine in a 1-week newborn, due to confusion between nevirapine (Viramune) and nelfinavir (Viracept). The drug was eliminated spontaneously and quickly. We only observed mild neutropenia and hyperlactatemia, which regressed on its own without any clinical complication. Despite the good evolution of this massive overdose, physicians should be aware of confusion risks between some antiretroviral drugs.