The history of antiretrovirals: key discoveries over the past 25 years

Clercq, Erik De

doi:10.1002/rmv.624

Cited by 160 publications

(101 citation statements)

References 77 publications

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“…Considering the different classes of anti-HIV drugs currently available [NRTIs, nucleotide reverse transcriptase inhibitors (NtRTIs), NNRTIs, protease inhibitors (PIs), fusion inhibitors (FIs), coreceptor inhibitors (CRIs), and integrase inhibitors (INIs)] (62,63), the number of possible multidrug combinations is unrealistically high (Figure 8). Yet the number of approved fixed-dose drug combinations is rather limited; the only one containing three different classes of compounds is Atripla R , which consists of 300 mg TDF (tenofovir disoproxil fumarate), Combination of anti-HIV drugs.…”

Section: Drug Combination Therapymentioning

confidence: 99%

A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

Clercq

2011

Annu. Rev. Pharmacol. Toxicol.

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My search for a selective antiviral chemotherapy started more than 40 years ago with interferon inducers, then shifted to nucleoside analogs with the discovery of BVDU (brivudin), a highly selective anti-HSV-1 and anti-VZV agent, and to dideoxynucleoside analogs such as d4T (stavudine), anti-HIV agents. The search culminated in the discovery of acyclic nucleoside phosphonates (ANPs) (in collaboration with Antonin Holý), a key class of compounds active against HIV, hepatitis B virus, and DNA viruses at large; the best known of these compounds is tenofovir. Along the way, the principle of the non-nucleoside reverse transcriptase inhibitors (NNRTIs) was established. This work, initiated in collaboration with the late Paul A.J. Janssen, eventually led to the identification of rilpivirine as perhaps an "ideal" NNRTI.1

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Section: Drug Combination Therapymentioning

confidence: 99%

A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

Clercq

2011

Annu. Rev. Pharmacol. Toxicol.

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150

144

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“…De Clercq's review (2010) shows that with Azidothymidine/Zidovudine (AZT) being the first antiretroviral drug used 25 years ago, ART has advanced significantly to advocate for three or four drugs to be used in a triple therapy combination. In this report, ART will be the term used to denote highlyactive active antiretroviral therapy (HAART), which has been available since 1996 in developed countries (De Clercq, 2009) (Simon, et al, 2006).…”

Section: Antiretroviral Therapy (Art)mentioning

confidence: 99%

Developmental delay in HIV-exposed infants in Harare, Zimbabwe

Hutchings¹,

Potterton

2013

Vulnerable Children and Youth Studies

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The aim of this cross-sectional study was to determine the difference in development (cognition; receptive and expressive language; and fine and gross motor) of Human Immunodeficiency Virus (HIV) -exposed infected (HEI) infants with the development of HIV-exposed but uninfected (HEU) infants using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Sixty infants were enrolled in the study; 32 (53.33%) HEU infants and 28 (46.67%) HEI infants. The two groups were well-matched for infant demographics, anthropometry at birth, maternal demographics, as well as socioeconomic status. Statistically significant differences were found in anthropometry and development between the HEI and HEU group. The HEI infants had malnutrition, were stunted and had smaller head circumferences than HEU infants. The BSID-III showed that the mean developmental delay for the HEI group was approximately two months below their mean chronological age for all scales (cognitive; receptive and expressive communication; and, fine and gross motor age).The HEI group showed that 64.29% had cognitive delay, 60.71% had language delay and 53.57% had motor delay, all of which was significantly different from the development of the HEU group for all domains (p<0.001). In addition to using the BSID-III, the majority of mothers were able to correctly indicate whether their child was developing at the same, or at a slower rate of development than children of the same age. This study demonstrates that infants who are HIV-exposed and infected are at risk of developmental delay.

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“…Also HAART can successfully prevent aids-related morbidity and mortality, resulting in increased lifespan of HIV-infected patients. In turn, the course of HIV disease has evolved from a universally fatal infection to a manageable chronic illness [55,56].…”

Section: Oxidative Stress During Antiretroviral Treatmentmentioning

confidence: 99%

“…Additional adverse effects and/or regimen adherence difficulties have serious consequences such as loss of serum HIV suppression, development of drug-resistant HIV strains, and increased probability of opportunistic illness develop [60]. NRTI are associated with lactic acidosis, hyperlipidemia, glucose intolerance, diabetes mellitus, atherosclerosis, fat redistribution and wasting syndrome; all of these could be related to increased OS and its toxicity [31,55,64]. Phophorylated-NRTI mitochondrial toxicity may amplify some of the pathophysiologic and phenotypical events in infection.…”

Section: Oxidative Stress During Antiretroviral Treatmentmentioning

confidence: 99%

Altered Redox Regulation as Cofactor in Comorbidities and Accelerated Aging in HIV Infection Evolution and Antiretroviral Treatment

Valle¹

2014

Epidemiol

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Metabolic issues persist in HIV patients who are otherwise stable with and without antiretroviral treatment. Metabolic alterations are associated to chronic inflammation, severe mitochondrial toxicity and oxidative stress as critical factors influencing HIV disease outcomes even during antiretroviral treatment. These aspects could also be involved in comorbidities and premature aging. Both factors should be managed during therapy and they should be focus of intense ongoing investigation.The aim of this mini-review is to describe essential mechanisms of in vivo reactive oxygen species generation, antioxidants pathways, and oxidative stress involved in HIV disease. Potential impact on reactive oxygen species, oxidative damage, cellular function, and how these responses change could mediate aging in pathophysiological situations are discussed. Accrual experimental and clinical reports analyses allow us a better understanding of various inter-related contributing factors. In addition, oxidative stress as an often-overlooked link between HIVinfection and the progression of aids, during antiretroviral treatment, is analyzed. Potential long-term consequences of antioxidant treatment require on-going investigation in order to obtain important clinical issues that have recently been reported. Currently, the most practical advice is to start antiretroviral therapy early and to manage traditional risk factors of non-aids-related conditions.

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The history of antiretrovirals: key discoveries over the past 25 years

Cited by 160 publications

References 77 publications

A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

Developmental delay in HIV-exposed infants in Harare, Zimbabwe

Altered Redox Regulation as Cofactor in Comorbidities and Accelerated Aging in HIV Infection Evolution and Antiretroviral Treatment

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