Tolerability of HIV integrase inhibitors

Lee, Frederick J.; Carr, Andrew

doi:10.1097/coh.0b013e328356682a

Cited by 36 publications

(17 citation statements)

References 31 publications

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“…145 This could relate to the fact that they have only recently been brought into the pharmacopoeia. Evidence exists for a side effect of dyslipidemia, which could be considered a risk factor for increased cardiovascular disease, but are generally acceptable for clinical use.…”

Section: Other Antiretroviral Side Effects: Aging and Pismentioning

confidence: 99%

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Aging and HIV/AIDS: pathogenetic role of therapeutic side effects

Torres

Lewis

2014

Laboratory Investigation

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The intersection of aging and HIV/AIDS is a looming ‘epidemic within an epidemic.’ This paper reviews how HIV/AIDS and its therapy cause premature aging or contribute mechanistically to HIV-associated non-AIDS illnesses (HANA). Survival with HIV/AIDS has markedly improved by therapy combinations containing nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors, and protease inhibitors (PIs) called HAART (highly active anti-retroviral therapy). Because NRTIs and PIs together prevent or attenuate HIV-1 replication, and prolong life, the population of aging patients with HIV/AIDS increases accordingly. However, illnesses frequently associated with aging in the absence of HIV/AIDS appear to occur prematurely in HIV/AIDS patients. Theories that help to explain biological aging include oxidative stress (where mitochondrial oxidative injury exceeds antioxidant defense), chromosome telomere shortening with associated cellular senescence, and accumulation of lamin A precursors (a nuclear envelop protein). Each of these has the potential to be enhanced or caused by HIV/AIDS, antiretroviral therapy, or both. Antiretroviral therapy has been shown to enhance events seen in biological aging. Specifically, antiretroviral NRTIs cause mitochondrial dysfunction, oxidative stress, and mitochondrial DNA defects that resemble features of both HANA and aging. More recent clinical evidence points to telomere shortening caused by NRTI triphosphate-induced inhibition of telomerase, suggesting telomerase reverse transcriptase (TERT) inhibition as being a pathogenetic contributor to premature aging in HIV/AIDS. PIs may also have a role in premature aging in HIV/AIDS as they cause prelamin A accumulation. Overall, toxic side effects of HAART may both resemble and promote events of aging and are worthy of mechanistic studies.

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Section: Other Antiretroviral Side Effects: Aging and Pismentioning

confidence: 99%

“…Evidence exists for a side effect of dyslipidemia, which could be considered a risk factor for increased cardiovascular disease, but are generally acceptable for clinical use. 145,146 …”

Section: Other Antiretroviral Side Effects: Aging and Pismentioning

confidence: 99%

Aging and HIV/AIDS: pathogenetic role of therapeutic side effects

Torres

Lewis

2014

Laboratory Investigation

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“…In addition, treatment-experienced HIV-infected patients had comparable results when switched from raltegravir to an elvitegravir-containing regimen [46,52,[56][57][58]. A completed phase IIIb non-inferiority trial enrolling adults already suppressed on efavirenz or nevirapine or rilpivirine plus tenofovir/emtricitabine who were randomized to either remain in their current regimen or switch to elvitegravir/cobicistat/emtricitibine/tenofovir suggested that at 48 weeks (endpoint HIV RNA \50 copies/mL) the switch appeared efficacious and welltolerated with no emergent resistance.…”

Section: Elvitegravir Use In Adultsmentioning

confidence: 76%

Use of Integrase Inhibitors in HIV-Infected Children and Adolescents

Dehority

Abadi

Wiznia

et al. 2015

Drugs

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Resistance to antiretroviral drugs is an increasingly prevalent challenge affecting both the adult and pediatric HIV-infected populations. Though data on the safety, pharmacokinetics, and efficacy of newer antiretroviral agents in children typically lags behind adult data, newer agents are becoming available for use in HIV-infected children who are failing to respond to or are experiencing toxicities with traditional antiretroviral regimens. Integrase strand transfer inhibitors are one such new class of antiretrovirals. Raltegravir has been US Food and Drug Administration (FDA) approved for use in patients over the age of 4 weeks. Elvitegravir is a second member of this class, and has the potential for use in children but does not yet have a Pediatric FDA indication. Dolutegravir, a second-generation integrase inhibitor, is approved for those older than 12 years. This review summarizes the use of integrase inhibitors in children and adolescents, and highlights the results of recent clinical trials.

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“…The most common AEs seen with the use of INSTIs are gastrointestinal disturbances, such as diarrhea and nausea, but headache is also a common AE [61]. In addition, INSTIs have shown infrequent lipid elevations and low rates of metabolic abnormalities [61,62]. Nevertheless, raltegravir has been associated with creatinine phosphokinase (CPK) elevations and cobicistat, in the elvitegravir single-tablet formulation, is associated with benign increases in serum creatinine [61].…”

Section: Safetymentioning

confidence: 99%

Clinical pharmacokinetics and pharmacodynamics of dolutegravir used as a single tablet regimen for the treatment of HIV-1 infection

Bollen

Reiss

Schapiro

et al. 2015

Expert Opinion on Drug Safety

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The dolutegravir/abacavir/lamivudine regimen is highly effective in achieving sustained suppression of HIV-1 RNA plasma concentrations. The STR has a favorable safety profile and a low potential for drug interactions, which will contribute to a prominent role in therapy. As this STR contains abacavir as backbone component, the use requires patients to be HLA-B*5701 negative, with good hepatic function. Other first-line treatment combinations are preferred for patients with hepatitis B co-infection or with a high cardiovascular risk.

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Tolerability of HIV integrase inhibitors

Abstract: INSTIs are an important recent addition to the antiretroviral armamentarium, with good short-term and medium-term safety. Long-term data from ongoing clinical studies are needed for a definitive assessment of their safety profile.

Cited by 36 publications

References 31 publications

Aging and HIV/AIDS: pathogenetic role of therapeutic side effects

Aging and HIV/AIDS: pathogenetic role of therapeutic side effects

Use of Integrase Inhibitors in HIV-Infected Children and Adolescents

Clinical pharmacokinetics and pharmacodynamics of dolutegravir used as a single tablet regimen for the treatment of HIV-1 infection

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