High virologic response rate after second-line boosted protease inhibitor-based antiretroviral therapy regimens in children from a resource limited setting

Puthanakit, Thanyawee; Jourdain, Gonzague; Suntarattiwong, Piyarat; Chokephaibulkit, Kulkanya; Siangphoe, Umaporn; Prasitsuebsai, Wasana; Sirisanthana, Virat; Kosalaraksa, Pope; Petdachai, Witaya; Hansudewechakul, Rawiwan; Ananworanich, Jintanat

doi:10.1186/1742-6405-9-20

Cited by 15 publications

(16 citation statements)

References 23 publications

(27 reference statements)

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“…Among patients who switched to second-line ART, an estimated 85% (95% CI [75-91]) remained continuously suppressed <400c/ml at 12 months and 73% (95% CI [62-82]) at 24 months after switch. These rates of suppression are comparable to recent reports from Thailand and Africa, where all patients initiated on a PIbased second line regimen [26][27][28] . Another study of paediatric response to second-line ART in South Africa showed significantly poorer VL suppression in children receiving NNRTI-based as opposed to PI-based second-line therapy 29 .…”

Section: Europe Pmc Funders Author Manuscriptssupporting

confidence: 75%

“…The median age, viral load, CD4 count, and CD4% at VL rebound were 10·6 years [5·6-13·4], 3·6 log 10 c/ml [3·1-4·2], 550 cells/μl , and 24% [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32], respectively, and three-quarters of children initiated on a NNRTI-based regimen. Fifty one (30%) had already experienced some ART modifications not meeting the definition of switch prior to VL rebound.…”

Section: Resultsmentioning

confidence: 99%

“…We identified 17 publications with data on children from a variety of settings which analysed either long-term virological patient outcomes 1,3,4,13,25 , durability of first-line ART 2,9,18,19,22 or response to second-line ART 8,23,24,[26][27][28][29] . Only two studies have reported outcomes following viral load rebound and the probability of switch or resuppression without switch in routine care 19,22 .…”

Section: Systematic Reviewmentioning

confidence: 99%

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Outcomes after viral load rebound on first-line antiretroviral treatment in children with HIV in the UK and Ireland: an observational cohort study

et al. 2015

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Section: Europe Pmc Funders Author Manuscriptssupporting

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Section: Systematic Reviewmentioning

confidence: 99%

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Outcomes after viral load rebound on first-line antiretroviral treatment in children with HIV in the UK and Ireland: an observational cohort study

et al. 2015

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“…This second-line regimen is associated with a high rate of virological suppression and immune reconstitution after 24 months of follow-up in adults from Cambodia, response to second-line ART in children, 40 this is a major concern, particularly due to the need for life-long treatment and the limited available subsequent drugs, restricting treatment management in these RLS.…”

Section: Coetzer Et Almentioning

confidence: 99%

Extensive Drug Resistance in HIV-Infected Cambodian Children Who Are Undetected as Failing First-Line Antiretroviral Therapy by WHO 2010 Guidelines

Coetzer

Westley

DeLong

et al. 2013

AIDS Research and Human Retroviruses

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Antiretroviral therapy in resource-limited settings is monitored clinically and immunologically according to WHO guidelines. Frequent misclassification of virologic failure is reported, mostly in adults, leading to early therapy switch or late failure diagnosis. Pediatric treatment monitoring and resistance data upon first-line failure are limited, particularly when the 2010-WHO pediatric guidelines are used without routine viral load monitoring. We previously reported high treatment failure misclassification rates by pediatric 2010 guidelines in Cambodian children on first-line therapy. Here we determine the extent and patterns of resistance, with yearly viral load and 6-monthly CD4. Drug resistance mutations were determined using the IAS-USA 2011 list. Predicted resistance interpretation was determined with Stanford Database tools. Fifty-one children with available genotypes met inclusion criteria. All but one (subtype B) were CRF01_AE. The most common regimen was stavudine, lamivudine, and nevirapine (96%), taken for a median of 2.2 years. Resistance was seen in 98%; 96% to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs); 51% with ‡ 4 mutations. The most common NRTI mutations were 184V/I and 67N and the most common NNRTI mutations were 181C/Y/I/V and 190A/S. A total of 22% had multiresistant mutations and 18% had predicted high-level resistance to subsequent therapy options didanosine, abacavir, etravirine, and tenofovir. In 98% of Cambodian children misclassified as nonfailing first-line therapy by 2010 guidelines, 51% had extensive drug resistance to current and 18% to subsequent antiretroviral therapy. Affordable routine viral load monitoring allowing for early and more accurate treatment failure diagnosis is desperately needed in resource-limited settings.

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“…Previous studies have demonstrated that continuing to maintain FTC or 3TC in the backbone of the second line regimen (SLR) has similar activity to using regimens with at least 2 other active NRTIs; 6,7 several studies suggest that SLR with protease inhibitors (PI) may be more effective. 8,9 Several reports have suggested that failure of second line therapy after developing M184V is due more to non-adherence, and not primarily to virologic failure (VF), 7,10 and that even the initial failing regimen may be used if adherence is improved. The purpose of this study was to describe the occurrence of the M184V mutation in a single clinic setting over a period of 10 years; to examine second line therapy choices, regarding VS, time to VS, and VF following virologic suppression (VS).…”

Section: Introductionmentioning

confidence: 99%

Development of the M184V Mutation in HIV-1 Infection and Subsequent Treatment Outcomes

Wilson¹,

Cross²,

Nurutdinova³

et al. 2015

HIV/AIDS Res Treat Open J

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CitationThe purpose of this study was to describe the occurrence of the M184V mutation in a single clinic setting over a period of 10 years. We examined the combination Antiretroviral Therapy (cART) being taken at the time of first identification of the M184V mutation as well as Second Line Regimens (SLR) started immediately after the documentation of M184V. SLR were evaluated for frequency and time to Virologic Suppression (VS) as well as frequency and time to subsequent Virologic Failure (VF). Prevalence of the M184V mutation, ART regimen leading to M184V acquisition, and outcomes of SLR in patients with M184V (as measured by time to initial VS and subsequent VF on SLR) were analyzed in a retrospective cohort study of all HIV-infected persons receiving care at a university clinic. Results: Of 2500 screened clinic patients, 220 had an acquired MI184V mutation (8.8%). There were 158(72%) male and 171(78%) African-American patients. The mean time from the start of a regimen to the documented M184V mutation was 575(0-3253) days. Independent of Nucleoside Reverse Transcriptase Inhibitor (NRTI) backbone, the mean time to development of M184V in Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) (n=109) and Protease Inhibitor (PI) based (n=84) regimens was 538(+/-556) and 622 (+/-620) days, respectively (p=0.325) approximately, 78% of patients achieved VS on a SLR in a mean of 179 days. Of the 122(57%) of patients whose SLR retained FTC/3TC, VS was achieved in 80% compared to 74% without FTC/3TC (p=0.285) with no significant difference in time to VS (152(+/-187) and 181(+/-257) days respectively, p=0.406). There were no significant differences in achievement of VS in PI (n=158) and NNRTI (n=27) -based SLRs independent of the NRTI backbone, 76% vs. 78%, respectively (p=0.837) with a similar time to VS (180(+/-228) vs. 128(+/-158) days, p=0.313). All patients on PI+Raltegravir (RAL) (n=10) and PI+NNRTI (n=12) -based regimens achieved VS (vs. 76% in PI+2NRTI (p=0.078 and p=0.054, respectively). Regardless of SLR, about 50% of each group experienced VF after VS with a similar time to failure. Conclusions: M184V mutation developed in 9% of patients in a mean of 575 days with no significant differences between ART regimens. Following initiation of an SLR, the majority of patients achieved VS in approximately 179 days irrespective of the regimen. The addition of 3TC/FTC did not significantly affect VS. Although numbers were small, 100% of patients on two fully active non-NRTI-backbone-based regimens attained VS. Approximately half of all patients subsequently failed on SLR, regardless of regimen used, suggesting that the development of M184V is a marker of noncompliance to therapy.

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High virologic response rate after second-line boosted protease inhibitor-based antiretroviral therapy regimens in children from a resource limited setting

Cited by 15 publications

References 23 publications

Outcomes after viral load rebound on first-line antiretroviral treatment in children with HIV in the UK and Ireland: an observational cohort study

Outcomes after viral load rebound on first-line antiretroviral treatment in children with HIV in the UK and Ireland: an observational cohort study

Extensive Drug Resistance in HIV-Infected Cambodian Children Who Are Undetected as Failing First-Line Antiretroviral Therapy by WHO 2010 Guidelines

Development of the M184V Mutation in HIV-1 Infection and Subsequent Treatment Outcomes

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