Incidence rate of modifying or discontinuing first combined antiretroviral therapy regimen due to toxicity during the first year of treatment stratified by age

Torres, Thiago Silva; Cardoso, Sandra Wagner; Velasque, Luciane; Veloso, Valdiléa G.; Grinsztejn, Beatriz

doi:10.1016/j.bjid.2013.04.005

Cited by 18 publications

(20 citation statements)

References 40 publications

(43 reference statements)

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“…A recent study from Torres et al . in Brazil noted a trend where rates of drug toxicities and ART modification during the first year of therapy increased with age 41. Consistent with this, we also found in this study a trend towards a slightly increased risk of ART modification in older adults within the first three years of ART initiation.…”

Section: Discussionsupporting

confidence: 90%

Virologic failure and mortality in older ART initiators in a multisite Latin American and Caribbean Cohort

Carriquiry¹,

Giganti

Castilho

et al. 2018

J Intern AIDS Soc

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IntroductionThe “greying” of the HIV epidemic necessitates a better understanding of the healthcare needs of older HIV‐positive adults. As these individuals age, it is unclear whether comorbidities and their associated therapies or the ageing process itself alter the response to antiretroviral therapy (ART). In this study, HIV treatment outcomes and corresponding risk factors were compared between older ART initiators and those who were younger using data from the Caribbean, Central and South America Network for HIV Epidemiology (CCASAnet).Methods HIV‐positive adults (≥18 years) initiating ART at nine sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Patients were classified as older (≥50 years) or younger (<50 years) based on age at ART initiation. ART effectiveness was measured using three outcomes: death, virologic failure and ART treatment modification. Cox regression models for each outcome compared risk between older and younger patients, adjusting for other covariates.ResultsAmong 26,311 patients initiating ART between 1996 and 2016, 3389 (13%) were ≥50 years. The majority of patients in both ≥50 and <50 age groups received a non‐nucleoside reverse transcriptase inhibitor‐based regimen (89% vs. 87%), did not have AIDS at baseline (63% vs. 62%), and were male (59% vs. 58%). Older patients had a higher risk of death (adjusted hazard ratio (aHR) 1.64; 95% confidence intervals (CI): 1.48 to 1.83) and a lower risk of virologic failure (aHR: 0.73; 95% CI: 0.63 to 0.84). There was no difference in risk of ART modification (aHR: 1.00; 95% CI: 0.94 to 1.06). Risk factors for death, virologic failure and treatment modification were similar for each group.ConclusionsOlder age at ART initiation was associated with increased mortality and decreased risk of virologic failure in our cohort of more than 26,000 ART initiators in Latin America and the Caribbean. To the best of our knowledge this is the first study from the region to evaluate ART outcomes in this growing and important population. Given the complexity of issues related to ageing with HIV, a greater understanding is needed in order to properly respond to this shifting epidemic.

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Section: Discussionsupporting

confidence: 90%

Virologic failure and mortality in older ART initiators in a multisite Latin American and Caribbean Cohort

Carriquiry¹,

Giganti

Castilho

et al. 2018

J Intern AIDS Soc

Self Cite

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“…Our analysis, however, did not include evaluations of antiretroviral-related toxicities or other adverse events which have been reported to be increased among older individuals and women including in our cohort [18], [27], [36], [37]. Despite this, 73.3% of the post-menopausal women and 71.3% of premenopausal women with HIV-1 RNA measurements were virologically suppressed at 24 months.…”

Section: Discussionmentioning

confidence: 94%

Absence of Effect of Menopause Status at Initiation of First-Line Antiretroviral Therapy on Immunologic or Virologic Responses: A Cohort Study from Rio de Janeiro, Brazil

et al. 2014

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ObjectiveTo compare the effectiveness of first-line combination antiretroviral therapy (cART) between premenopausal and postmenopausal women.MethodsART-naïve women initiating cART between January 2000/June 2010 at the Instituto de Pesquisa Clínica Evandro Chagas Cohort were studied. Women were defined as postmenopausal after 12 consecutive months of amenorrhea. CD4 cell counts and HIV-1 RNA viral load (VL) measurements were compared between pre- and postmenopausal at 6, 12 and 24 months after cART initiation. Women who modified/discontinued a drug class or died due to an AIDS defining illness were classified as ART-failures. Variables were compared using Wilcoxon test, χ2 or Fisher’s exact test. The odds of cART effectiveness (VL<400 copies/mL and/or no need to change cART) were compared using logistic regression. Linear model was used to access relationship between CD4 change and menopause.ResultsAmong 383 women, 328 (85%) were premenopausal and 55 (15%) postmenopausal. Median pre cART CD4 counts were 231 and 208 cells/mm3 (p = 0.14) in pre- and postmenopausal women, respectively. No difference in the median pre cART VL was found (both 4.8 copies/mL). Median CD4 changes were similar at 6 and 12 months. At 24 months after cART initiation, CD4 changes among postmenopausal women were significantly lower among premenopausal women (p = 0.01). When the analysis was restricted to women with VL<400 copies/mL, no statistical difference was observed. Overall, 63.7% achieved cART effectiveness at 24 months without differences between groups at 6, 12 and 24 months.ConclusionMenopause status at the time of first-line cART initiation does not impact CD4 cell changes at 24 months among women with a virologic response. No relationship between menopause status and virologic response was observed.

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“…Because of the limited efficiency of commonly used drugs and emerging resistance of viruses, antiviral peptides may have the potential for development as putative therapeutic agents [11]. In addition to their reduced market availability, the collateral effects and toxicity of the synthetic antiviral drugs have triggered an expanded search for natural compounds displaying antiviral activities [12,13]. Any compound to be utilized as an antiviral should comply with the virus pathways during the cellular infectious cycle.…”

Section: Possible Action Mechanism Of Antiviral Compoundsmentioning

confidence: 99%

“…Cecropins, isolated mostly from the hemolymph of infected pupae of the silk moth Hyalophora cecropia, but also from other insects, tunicates and Ascaris nematodes, are a family of AMPs, containing 35-37 amino acid residues arranged in two amphiphilic α-helices linked by a Gly-Pro hinge. Synthetic hybrid peptides, namely cecropin A (1-8)-magainin 2 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), exhibited potent antiviral activity by a mechanism mainly based on the compound hydrophobicity and α-helical content, inhibiting the virushost cell fusion [85] (Table 2).…”

Section: Insect Venomsmentioning

confidence: 99%

Antiviral activity of animal venom peptides and related compounds

Mata

Mourão

Rangel

et al. 2017

J Venom Anim Toxins Incl Trop Dis

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Viruses exhibit rapid mutational capacity to trick and infect host cells, sometimes assisted through virus-coded peptides that counteract host cellular immune defense. Although a large number of compounds have been identified as inhibiting various viral infections and disease progression, it is urgent to achieve the discovery of more effective agents. Furthermore, proportionally to the great variety of diseases caused by viruses, very few viral vaccines are available, and not all are efficient. Thus, new antiviral substances obtained from natural products have been prospected, including those derived from venomous animals. Venoms are complex mixtures of hundreds of molecules, mostly peptides, that present a large array of biological activities and evolved to putatively target the biochemical machinery of different pathogens or host cellular structures. In addition, non-venomous compounds, such as some body fluids of invertebrate organisms, exhibit antiviral activity. This review provides a panorama of peptides described from animal venoms that present antiviral activity, thereby reinforcing them as important tools for the development of new therapeutic drugs.

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Incidence rate of modifying or discontinuing first combined antiretroviral therapy regimen due to toxicity during the first year of treatment stratified by age

Cited by 18 publications

References 40 publications

Virologic failure and mortality in older ART initiators in a multisite Latin American and Caribbean Cohort

Virologic failure and mortality in older ART initiators in a multisite Latin American and Caribbean Cohort

Absence of Effect of Menopause Status at Initiation of First-Line Antiretroviral Therapy on Immunologic or Virologic Responses: A Cohort Study from Rio de Janeiro, Brazil

Antiviral activity of animal venom peptides and related compounds

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