Pan-resistant HIV-1 emergence in the era of integrase strand-transfer inhibitors: a case report

Puertas, María C.; Ploumidis, George; Ploumidis, Michalis; Fumero, Emilio; Clotet, Bonaventura; Walworth, Charles; Petropoulos, Christos J.; Martínez-Picado, Javier

doi:10.1016/s2666-5247(20)30006-9

Cited by 28 publications

(26 citation statements)

References 28 publications

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“…This question remains a conundrum of high public health concern. Examples of such coexistence include some of the most relevant human pathogens: antiviral resistance of the immunodeficiency virus (HIV) [ 53 , 54 ], antimalarial resistance to malaria parasites [ 55 ], drug and vaccine escape by Mycobacterium tuberculosis [ 56 ], and antimicrobial resistance in Streptococcus pneumoniae [ 19 , 33 , 57 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

Pneumococcal Competition Modulates Antibiotic Resistance in the Pre-Vaccination Era: A Modelling Study

et al. 2021

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The ongoing emergence of antibiotic resistant strains and high frequencies of antibiotic resistance of Streptococcus pneumoniae poses a major public health challenge. How and which ecological and evolutionary mechanisms maintain the coexistence of antibiotic resistant and susceptible strains remains largely an open question. We developed an individual-based, stochastic model expanding on a previous pneumococci modelling framework. We explore how between- and within-host mechanisms of competition can sustain observed levels of resistance to antibiotics in the pre-vaccination era. Our framework considers that within-host competition for co-colonization between resistant and susceptible strains can arise via pre-existing immunity (immunological competition) or intrinsic fitness differences due to resistance costs (ecological competition). We find that beyond stochasticity, population structure or movement, competition at the within-host level can explain observed resistance frequencies. We compare our simulation results to pneumococcal antibiotic resistance data in the European region using approximate Bayesian computation. Our results demonstrate that ecological competition for co-colonization can explain the variation in co-existence of resistant and susceptible pneumococci observed in the pre-vaccination era. Furthermore, we show that within-host pneumococcal competition can facilitate the maintenance of resistance in the pre-vaccination era. Accounting for these competition-related components of pneumococcal dynamics can improve our understanding of drivers for the emergence and maintenance of antibiotic resistance in pneumococci.

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Section: Discussionmentioning

confidence: 99%

Pneumococcal Competition Modulates Antibiotic Resistance in the Pre-Vaccination Era: A Modelling Study

et al. 2021

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“…This question remains a conundrum of high public health concern. Examples of such coexistence include some of the most relevant human pathogens: antiviral resistance of the immunodeficiency virus (HIV) [61,62] , antimalarial resistance to malaria parasites [63] , drug and vaccine escape by Mycobacterium tuberculosis [64] , and antimicrobial resistance in Streptococcus pneumoniae [34,37,41,65,66] .…”

Section: Discussionmentioning

confidence: 99%

Within-host competition modulates pneumococcal antibiotic resistance in the pre-vaccination era

Lourenço

Daon

Gori

et al. 2020

Preprint

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BackgroundAntibiotic treatment is a key tool in the fight against pneumococcal infections. However, the ongoing emergence of antibiotic resistant strains and high frequencies of antibiotic resistance of pneumococci pose a major public health challenge. How and which ecological and evolutionary mechanisms help maintain the coexistence of strains susceptible and resistant to antibiotic treatment remains largely an open question.Methods/resultsExpanding on a Streptococcus pneumoniae modelling framework, we here explore how both between- and within-host mechanisms of transmission can sustain observed levels of pneumococcal resistance to antibiotics in the pre-vaccination era using a stochastic, individual-based model. Our framework considers that within-host competition for co-colonization between resistant and susceptible strains can arise via pre-existing immunity (immunological competition) or intrinsic fitness differences due to resistance costs (ecological competition). We find that beyond stochasticity, host-population structure or movement at the between-host level, competition at the within-host level can explain observed variation in resistance frequencies.ConclusionIn a series of simulated scenarios informed by observed pneumococcal data in the European region, we demonstrate that ecological competition for co-colonization can explain much of the variation in co-existence observed at the country level in the pre-vaccination era. This work expands our understanding of how within-host pneumococcal competition facilitates the maintenance of antibiotic resistance in the pre-vaccination era. The demonstration of the effects of such underlying, often unmeasured competition-related components of pneumococcal dynamics improves our understanding of the mechanistic drivers for the emergence and maintenance of antibiotic resistance.

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“…These combinations also improve quality of life and decrease the risk of medication errors and drug resistance. [35] By and large, preventable ADR causes were prescription errors. Prescription errors were related to the fact that antiretrovirals were administered in fi xed-dose combinations and all patients did not tolerate them equally.…”

Section: Original Researchmentioning

confidence: 99%

Adverse Reactions to Antiretrovirals in Cuban Patients Living with HIV/AIDS

Morales-Pérez

2021

MEDICC Review

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INTRODUCTION Disease and deaths from HIV/AIDS have decreased since antiretroviral treatment was introduced in 1996. Since 2005, as treatment availability has increased worldwide, deaths from HIV/AIDS have declined 48%. As of November 2019, 26,952 cases have been reported in Cuba, of which 5159 (19.1%) are deceased. The country has experienced a reduction in mortality rates since 2002, when antiretroviral treatment became available. Although there are clearly benefi ts to treatment, it is important to understand antiretroviral safety profi les as their toxicity may lower treatment adherence. OBJECTIVE Describe adverse reactions attributable to antiretrovirals used in Cuban patients living with HIV/AIDS. METHODS I studied notifi cations of adverse reactions to antiretrovirals used in Cuban patients with HIV/AIDS from January 2003 to December 2017. The sample consisted of 352 notifi cations in the National Pharmacovigilance Database regarding adverse reactions attributed to antiretrovirals. The variables considered were sex, notifi cation year, antiretroviral drug, and number, type, frequency and severity of adverse reactions, whether or not they were preventable, and the reasons for categorizing them as they were. RESULTS Antiretrovirals reported an average adverse reaction rate of 2.1 per million population per year, representing 24.2% of adverse reactions produced by the antiviral drug group in that period. Adult males represented 75% (264/352) of patients who had adverse reactions to antiretrovirals. Most adverse reactions were in response to nevirapine (29.0%; 102/352) and zidovudine (26.7%; 94/352). The most frequent reactions were hypersensitivity (24.4%; 86/352), digestive disorders (15.9%; 56/352) and anemia (15.6%; 55/352). Reactions were common (62.5%; 220/352) and moderate in severity (70.4%; 248/352). Preventable reactions made up 52.6% (185/352) of adverse reactions. Of preventable reactions, 68.1% (126/185) were associated with drug interactions and 16.2% (30/185) with improper dosage or prescription errors.CONCLUSIONS Adverse reactions to antiretrovirals in Cuban patients are common and moderate in severity. The drug with the most notifi cations was nevirapine, and the most common adverse reaction was hypersensitivity. More than half of adverse reactions are considered preventable, and their main causes are prescription errors.

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Pan-resistant HIV-1 emergence in the era of integrase strand-transfer inhibitors: a case report

Cited by 28 publications

References 28 publications

Pneumococcal Competition Modulates Antibiotic Resistance in the Pre-Vaccination Era: A Modelling Study

Pneumococcal Competition Modulates Antibiotic Resistance in the Pre-Vaccination Era: A Modelling Study

Within-host competition modulates pneumococcal antibiotic resistance in the pre-vaccination era

Adverse Reactions to Antiretrovirals in Cuban Patients Living with HIV/AIDS

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