Analysis of HIV- type 1 protease and reverse transcriptase in Brazilian children failing highly active antiretroviral therapy (HAART)

Machado, Daisy Maria; Fernandes, Silvana; Succi, Regina Célia de Menezes; Freire, Wilton S.; Pannuti, Cláudio Sérgio; Gouveia, Aída Barbosa; Levi, José Eduardo; Diaz, Ricardo S.

doi:10.1590/s0036-46652005000100001

Cited by 22 publications

(16 citation statements)

References 12 publications

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“…We observed that the UPAM mutations V82A/F/L/T, I84V and L90M increased in frequency with increased numbers of therapeutic failures [27]. However, this was not observed for Lopinavir [28]. We found differences in resistance to the NRTI class of drugs in the multi-failure group compared with the primary and secondary failure groups.…”

Section: Discussionmentioning

confidence: 72%

Impact of the number of failed therapeutic regimes on the development of resistance mutations to HIV-1 in northeast Brazil

et al. 2007

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Highly-potent antiretroviral therapy is necessary to avoid viral replication in HIV patients; however, it can favor the appearance of resistance mutations. The mutations 41L, 67N, 70R, 210W, 215Y/F, 219E/Q, 44D and 118I are defined as nucleoside analogous mutations (NAMs), because they affect the efficacy of all nucleoside reverse transcriptase inhibitors (NRTI). The mutation most frequently associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) is 103N. 33W/F, 82A/F/L/T, 84V and 90M are called protease inhibitor resistance-associated mutations (PRAM), because they are associated with resistance to several protease inhibitors (PI). This study evaluated the development of resistance mutations and examine the susceptibility of HIV with these mutations to antiretrovirals in HIV-1 patients who have failed one or more therapy regimes. Analyses were made of 101 genotypic tests of patients with therapeutic failure to 2 or 3-drug regimens with NRTI, NNRTI or PI. We used the Stanford database to define the susceptibility profile of the viruses. The samples were divided into three treatment-failure groups: first (F), second (S) and multi-failure (MF) to antiretroviral regimens, and we correlated these groups with resistance profiles and principal mutations. There was a significant increase in resistance mutations V82A/F/L/T, I84V, L90M, M41L, K70R, L210W, T215Y/F and K219Q/E in MF. We also found significantly higher resistance to zidovudine, didanosine, stavudine and abacavir in MF. There was no increase in resistance to tenofovir (p=0.28) and lopinavir (p=0.079) in MF. A high degree of resistance to NNRTIs was observed in all groups. Increased resistance mutations will affect future therapeutic options for HIV patients in Brazil because it results in a significant increase in resistance to antiretroviral drugs.

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Section: Discussionmentioning

confidence: 72%

Impact of the number of failed therapeutic regimes on the development of resistance mutations to HIV-1 in northeast Brazil

et al. 2007

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“…Current knowledge of HIV drug resistance is mostly from developed countries with predominantly HIV-1 subtype B virus, showing mainly the consequences of sequential, non-suppressive regimens. 6,14 In contrast, much less information is available from sub-Saharan Africa regarding drug resistance in predominantly HIV-1 subtype C infection. 3 The high burden of concomitant HIV-disease and tuberculosis in African children complicates patient management and contributes to adverse patient outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…5 Prolonged non-suppressive ART increases the risk of acquiring additional viral mutations, with subsequent increased cross-resistance and drug failure over time. 6 Mutations conferring PI resistance are uncommon, but higher rates of PI mutations have been observed in children, compared with adults. 7 Known factors that increase the risk of HIV drug resistance in children include higher baseline HIV-1 viral loads (VL), complex adherence issues, inadequate pharmacokinetic information and unavailability of suitable pediatric ART formulations.…”

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confidence: 99%

Consequences of Prior Use of Full-dose Ritonavir as Single Protease Inhibitor as Part of Combination Antiretroviral Regimens on the Future Therapy Choices in HIV-1–Infected Children

Feucht¹,

Rossouw²,

Dyk³

et al. 2014

Pediatric Infectious Disease Journal

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“…These findings concur with previous reports from other pediatric cohorts in Brazil. [3][4][5] One of the difficulties in the interpretation and generalizability of these findings is the limited information on duration of treatment failure. Although the authors state that the median duration of ART in those failing therapy was 60 months, where failure was defined either as a decrease in viral …”

Section: Hiv Drug Resistance In Hiv-infected Childrenmentioning

confidence: 99%

Resistência aos medicamentos contra o HIV em crianças infectadas pelo vírus

Easterbrook¹

2009

J. Pediatr. (Rio J.)

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The global roll-out of antiretroviral therapy (ART) in children still lags significantly behind that of adults, and data on treatment outcomes from resource-limited settings have only recently begun to emerge. As a result, while there is a wealth of literature on patterns of drug resistance in adults on ART, there is still limited data on children. (17.4%), but these were present in all 12 children that were failing on NNRTIs. The most commonly used protease inhibitors (PIs) were unboosted -ritonavir and nelfinavir -, and primary PI resistance mutations were observed in 47.8%, particularly V82A, M46I, and L90M. These findings concur with previous reports from other pediatric cohorts in Brazil. [3][4][5]

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Analysis of HIV- type 1 protease and reverse transcriptase in Brazilian children failing highly active antiretroviral therapy (HAART)

Cited by 22 publications

References 12 publications

Impact of the number of failed therapeutic regimes on the development of resistance mutations to HIV-1 in northeast Brazil

Impact of the number of failed therapeutic regimes on the development of resistance mutations to HIV-1 in northeast Brazil

Consequences of Prior Use of Full-dose Ritonavir as Single Protease Inhibitor as Part of Combination Antiretroviral Regimens on the Future Therapy Choices in HIV-1–Infected Children

Resistência aos medicamentos contra o HIV em crianças infectadas pelo vírus

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