Incidence of Resistance in a Double‐Blind Study Comparing Lopinavir/Ritonavir Plus Stavudine and Lamivudine to Nelfinavir plus Stavudine and Lamivudine

Kempf, Dale J.; King, Martin; Bernstein, Barry; Cernohous, Paul; Bauer, E. D.; Moseley, Jennifer L.; Gu, Kai; Hsu, Ann; Brun, Scott; Sun, Eugene

doi:10.1086/380509

Cited by 202 publications

(173 citation statements)

References 31 publications

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“…Our finding reinforces the concept that ongoing viral replications [26] and few treatment options are associated with an increased probability of disease progression [27]. It has been reported that the use of boosted protease inhibitors (Boosted PI) is associated with multiple clinical benefits, including higher efficacy against resistant HIV strains [28], lower rates of resistance emergence at highadherence levels [29] and a lack of PI-associated resistance mutations after virologic failure in treatment-naïve patients [30]. As well, studies have shown that Boosted PI offers a marginal independent protective effect on disease progression [23,31].…”

Section: Discussionsupporting

confidence: 86%

Effect of Viral Load and Drug Resistance on Mortality among Chinese HIV-Infected Patients Receiving Antiretroviral Treatment

Wang¹,

Xing²,

Ruan³

et al. 2012

J Antivir Antiretrovir

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Background: The Chinese National Free Antiretroviral Treatment Program (NFATP) for HIV-infected patients has saved lives. However, there is no data on the effect of HIV drug resistance on mortality among Chinese patients receiving antiretroviral treatment. Methods:We linked patient records from two national databases: baseline HIV drug resistance and viral load data were obtained from four national drug resistance surveys in 2004, 2005, 2006 and 2009, and all-cause mortality was ascertained in a prospective way in NFATP database. Factors associated with death were identified by Cox regression model.

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Section: Discussionsupporting

confidence: 86%

Effect of Viral Load and Drug Resistance on Mortality among Chinese HIV-Infected Patients Receiving Antiretroviral Treatment

Wang¹,

Xing²,

Ruan³

et al. 2012

J Antivir Antiretrovir

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“…Traditionally, PIs are drugs characterized by a high genetic barrier to resistance [37][38][39], and thus generally associated with a lower emergence of drug resistance at virological failure [39][40][41]. For this reason, they are preferentially used in patients with high viral load.…”

Section: Discussionmentioning

confidence: 99%

Impact of Pre-Therapy Viral Load on Virological Response to Modern First-Line Haart

et al. 2013

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Background: We tested whether pre-HAART viraemia affects the achievement and maintenance of virological success in HIV-1-infected patients starting modern firstline therapies. Methods: A total of 1,430 patients starting their first HAART (genotype-tailored) in 2008 (median; IQR: 2006-2009) were grouped according to levels of pre-HAART viraemia (≤30,000, 30,001-100,000, 100,001-300,000, 300,001-500,000 and >500,000 copies/ml). The impact of pre-therapy viraemia on the time to virological success (viraemia ≤50 copies/ml) and on the time to virological rebound (first of two consecutive viraemia values >50 copies/ml after virological success) were evaluated by Kaplan-Meier curves and Cox regression analyses. Results: Median pre-HAART viraemia was 5.1 log 10 copies/ml (IQR 4.5-5.5), and 53% of patients had viraemia >100,000 copies/ml. By week 48, the prevalence of patients reaching virological success was >90% in all pre-HAART viraemia ranges, with the only exception of range >500,000 copies/ml (virological success =83%; P<0.001). Higher pre-HAART viraemia was tightly correlated with longer median time to achieve virological success. Cox multivariable estimates confirmed this result: patients with pre-HAART viraemia >500,000 copies/ml showed the lowest hazard of virological undetectability after adjusting for age, gender, pre-HAART CD4 + T-cell count, transmitted drug resistance, calendar year and third drug administered (adjusted hazard ratio [95% CI]: 0.27 [0.21, 0.35]; P<0.001). Pre-HAART viraemia >500,000 copies/ml was also associated with higher probability of virological rebound compared with patients belonging to lower viraemia strata at weeks 4, 12 and 24 (P=0.050). Conclusions: At the time of modern HAART, and even though an average >90% of virological success, high pre-HAART viraemia remains an independent factor associated with delayed and decreased virological success. Patients starting HAART with >500,000 copies/ml represent a significant population that may deserve special attention.HAART has significantly extended the time to development of AIDS and to death in HIV-infected individuals [1,2]. Its efficacy in suppression of plasma HIV-1 RNA to undetectable levels, and in increasing CD4 + T-cell count, is well documented in several clinical trials [3][4][5][6].Despite years of great progress in treating AIDS, however, in some patients starting their first treatment; the effectiveness of HAART is still not sufficient, with consequent virological failures [7][8][9]. These failures can be caused by several factors, such as drug potency, drug

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“…[22][23][24] Complicating these decisions is the relative paucity of data regarding the rate at which anti-retroviral resistance develops after the onset of virologic treatment failure in patients receiving highly active anti-retroviral therapy (HAART). [25][26][27] The purpose of this study was to define the time to accrual of genotypic resistance mutations, particularly thymidine analogue mutations (TAMs) and major protease inhibitor mutations, in persons with a persistently detectable plasma viral load (pVL) despite being on a stable antiretroviral regimen. We also sought to evaluate the impact of co-administration of lamivudine on the emergence of TAMs given the detrimental effect of the 184V mutation on HIV replication capacity, especially in combination with TAMs.…”

mentioning

confidence: 99%

Evolution of HIV Resistance Mutations in Patients Maintained on a Stable Treatment Regimen After Virologic Failure

Goetz¹,

Ferguson²,

Han³

et al. 2006

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective-We compared the rate of emergence of thymidine analogue mutations (TAMs) and major protease inhibitor mutations in adherent patients who remained on stable treatment with a thymidine analogue and/or protease inhibitor after the onset of virologic failure.Design-Follow-up genotypic resistance testing was done using archived plasma obtained from patients having 0 or 1 TAM and/or 0 or 1 major protease inhibitor resistance mutation at the onset of virologic failure.Results-The median duration of observed failure was 691 days. There were 41 thymidine analogue regimens and 34 protease inhibitor regimens; concomitant ritonavir was used 4 times. New major protease inhibitor mutations emerged more rapidly than did new TAMs (P = 0.0019); new TAMs emerged more rapidly in thymidine analogue regimens that did not include lamivudine (P = 0.0073). The emergence of TAMs and major protease inhibitor mutations did not differ if lamivudine was not part of the thymidine analogue regimen. The evolution of CD4 + cell counts and plasma viral loads (pVLs) during virologic failure was similar regardless of whether or not a new TAM or major protease inhibitor mutations emerged or, for thymidine analogue-containing regimens, whether lamivudine was or was not used.Conclusions-Major protease inhibitor mutations arose more frequently and rapidly than did TAMs in patients with sustained virologic failure who received lamivudine.

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Incidence of Resistance in a Double‐Blind Study Comparing Lopinavir/Ritonavir Plus Stavudine and Lamivudine to Nelfinavir plus Stavudine and Lamivudine

Cited by 202 publications

References 31 publications

Effect of Viral Load and Drug Resistance on Mortality among Chinese HIV-Infected Patients Receiving Antiretroviral Treatment

Effect of Viral Load and Drug Resistance on Mortality among Chinese HIV-Infected Patients Receiving Antiretroviral Treatment

Impact of Pre-Therapy Viral Load on Virological Response to Modern First-Line Haart

Evolution of HIV Resistance Mutations in Patients Maintained on a Stable Treatment Regimen After Virologic Failure

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