A Randomized Comparison of Second-Line Lopinavir/ Ritonavir Monotherapy versus Tenofovir/Lamivudine/ Lopinavir/Ritonavir in Patients Failing Nnrti Regimens: The HIV Star Study

Bunupuradah, Torsak; Chetchotisakd, Ploenchan; Ananworanich, Jintanat; Munsakul, Warangkana; Jirajariyavej, Supunnee; Kantipong, Pacharee; Prasithsirikul, Wisit; Sungkanuparph, Somnuek; Bowonwatanuwong, Chureeratana; Klinbuayaem, Virat; Kerr, Stephen J.; Sophonphan, Jiratchaya; Bhakeecheep, Sorakij; Hirschel, Bernard; Ruxrungtham, Kiat

doi:10.3851/imp2443

Cited by 47 publications

(17 citation statements)

References 32 publications

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“…29,30 In children, this strategy has been evaluated in virologically suppressed children, with promising results. 31 PI monotherapy would have several advantages such as fewer pills, fewer drug interactions, and less NRTIassociated toxicity.…”

Section: Discussionmentioning

confidence: 97%

Short Communication: High Rates of Thymidine Analogue Mutations and Dual-Class Resistance Among HIV-Infected Ugandan Children Failing First-Line Antiretroviral Therapy

Sigaloff

Kayiwa

Musiime

et al. 2013

AIDS Research and Human Retroviruses

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HIV-infected children are at high risk of acquiring drug-resistant viruses, which is of particular concern in settings where antiretroviral drug options are limited. We aimed to assess resistance patterns and predict viral drug susceptibility among children with first-line antiretroviral therapy (ART) failure in Uganda. A cross-sectional analysis of children switching ART regimens due to first-line failure was performed at three clinical sites in Uganda. HIV-RNA determination and genotypic resistance testing on all specimens with HIV-RNA >1,000 copies/ml were performed. Major drug resistance mutations were scored using the 2011 International Antiviral Society-USA list. The Stanford algorithm was used to predict drug susceptibility. At the time of switch, 44 genotypic resistance tests were available for 50 children. All children harbored virus with nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance [95% confidence interval (CI) 92-100%] and NRTI resistance was present in 98% (95% CI 88-100%). Forty-six percent (95% CI 30-61%) of children harbored ≥2 thymidine analog mutations. M184V was identified as the only NRTI mutation in 27% (95% CI 15-43%). HIV susceptibility to NRTIs, with the exception of tenofovir, was reduced in ≥60% of children. Ugandan children experiencing first-line ART failure in our study harbored high rates of dual-class and accumulated HIV drug resistance. Methods to prevent treatment failure, including adequate pediatric formulations and alternative second-line treatment options, are urgently needed.

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Section: Discussionmentioning

confidence: 97%

Short Communication: High Rates of Thymidine Analogue Mutations and Dual-Class Resistance Among HIV-Infected Ugandan Children Failing First-Line Antiretroviral Therapy

Sigaloff

Kayiwa

Musiime

et al. 2013

AIDS Research and Human Retroviruses

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“…WHO's preferred strategy for second-line ART, based on two NRTIs + bPI combination, when NNRTI-containing regimens are used in first line, has been validated in recent clinical trials [ 4 – 6 ], but evidence for the choice of combinations is deemed of low quality and is derived from settings in high-resource countries [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…Guidelines issued by the WHO in 2013 [ 3 ] recommend a second-line regimen based on boosted protease inhibitors (bPIs), with two nucleoside reverse transcriptase inhibitors (NRTIs), after failure of a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line treatment. This strategy was recently validated in three randomized clinical trials [ 4 – 6 ], but data on the NRTI and bPI options are lacking. In the WHO recommendations, the possible choice of bPI is between ritonavir-boosted atazanavir (ATZ/r) and ritonavir-boosted lopinavir (LPV/r), whereas ritonavir-boosted darunavir (DRV/r), considered as an option by the WHO expert panel, is finally not recommended due to non-availability as a generic co-formulation, its high price and limited registration [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of three second-line antiretroviral regimens in HIV-infected patients in Africa

Ciaffi

Koulla‐Shiro

Sawadogo

et al. 2015

Aids

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Objective:WHO recommends ritonavir-boosted protease inhibitor with two nucleoside reverse transcriptase inhibitors in HIV-infected patients failing non-nucleoside reverse transcriptase inhibitor-based first-line treatment. Here, we aimed to provide more evidence for the choice of nucleoside reverse transcriptase inhibitor and boosted protease inhibitor.Design:ANRS 12169 is a 48-week, randomized, open-label, non-inferiority trial in three African cities, comparing efficacy and safety of three second-line regimens.Methods:Patients failing non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy with confirmed plasma HIV-1 viral load above 1000 copies/ml were randomly assigned to tenofovir/emtricitabine + lopinavir/ritonavir (control group as per WHO recommendations), abacavir + didanosine + lopinavir/ritonavir (ABC/ddI group) or tenofovir/emtricitabine + darunavir/ritonavir (DRV group) regimens. The primary endpoint was the proportion of patients with plasma vral load below 50 copies/ml at week 48 in the modified intention-to-treat population. Non-inferiority was pre-specified with a 15% margin.Results:Of the 454 randomized patients, 451 were included in the analysis. Globally, 294 (65.2%) and 375 (83.2%) patients had viral load below 50 and 200 copies/ml, respectively, at week 48. The primary endpoint was achieved in 105 (69.1%) control group patients versus 92 (63.4%) in the ABC/ddI (difference 5.6%, 95% confidence interval –5.1 to 16.4) and 97 (63.0%) in the DRV (difference 6.1%, 95% confidence interval –4.5 to 16.7) groups (non-inferiority not shown). Overall, less number of patients with baseline viral load at least 100 000 copies/ml (n = 122) had a viral load below 50 copies/ml at week 48 (37.7 versus 75.4%; P < 0.001).Conclusions:The three second-line regimens obtained similar and satisfactory virologic control and confirmed the WHO recommendation (TDF/FTC/LPVr) as a valid option. However, the suboptimal response for patients with high viral load warrants research for improved strategies.

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“…The SECOND-LINE and EARNEST studies recently showed that second-line regimens consisting of a boosted-protease inhibitor plus 2 NRTIs/NtRTIs and boosted-protease inhibitor plus raltegravir led to favorable treatment outcomes for patients with HIV after initial NNRTI-based regimen failure [ 67 , 68 ]. In protease inhibitor-naive patients failing NNRTI-based first-line ART, mono-therapy with ritonavir-boosted lopinavir had a significantly lower proportion of patients with undetectable viral load compared to the ritonavir-boosted lopinavir plus tenofovir and lamivudine [ 69 ]. Thus, ritonavir-boosted lopinavir monotherapy is not recommended as a second-line option.…”

Section: Introductionmentioning

confidence: 99%

Guidelines for antiretroviral therapy in HIV-1 infected adults and adolescents 2014, Thailand

et al. 2015

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New evidence has emerged regarding when to commence antiretroviral therapy (ART), optimal treatment regimens, management of HIV co-infection with opportunistic infections, and management of ART failure. The 2014 guidelines were developed by the collaborations of the Department of Disease Control, Ministry of Public Health (MOPH) and the Thai AIDS Society (TAS). One of the major changes in the guidelines included recommending to initiating ART irrespective of CD4 cell count. However, it is with an emphasis that commencing HAART at CD4 cell count above 500 cell/mm3 is for public health, in term of preventing HIV transmission and personal benefit. In tuberculosis co-infected patients with CD4 cell counts ≤50 cells/mm3 or with CD4 cell counts >50 cells/mm3 who have severe clinical disease, ART should be initiated within 2 weeks of starting tuberculosis treatment. The preferred initial ART regimen in treatment naïve patients is efavirenz combined with tenofovir and emtricitabine or lamivudine. Plasma HIV viral load assessment should be done twice a year until achieving undetectable results; and will then be monitored once a year. CD4 cell count should be monitored every 6 months until CD4 cell count ≥350 cells/mm3 and with plasma HIV viral load <50 copies/mL; then it should be monitored once a year afterward. HIV drug resistance genotypic test is indicated when plasma HIV viral load >1,000 copies/mL while on ART. Ritonavir-boosted lopinavir or atazanavir in combination with optimized two nucleoside-analogue reverse transcriptase inhibitors is recommended after initial ART regimen failure. Long-term ART-related safety monitoring has also been included in the guidelines.Electronic supplementary materialThe online version of this article (doi:10.1186/s12981-015-0053-z) contains supplementary material, which is available to authorized users.

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A Randomized Comparison of Second-Line Lopinavir/ Ritonavir Monotherapy versus Tenofovir/Lamivudine/ Lopinavir/Ritonavir in Patients Failing Nnrti Regimens: The HIV Star Study

Abstract: In PI-naive patients failing NNRTI-based first-line HAART, mono-LPV/r had a significantly lower proportion of patients with HIV RNA<50 copies/ml compared to the TDF/3TC/LPV/r treatment. Thus, mono-LPV/r should not be recommended as a second-line option.

Cited by 47 publications

References 32 publications

Short Communication: High Rates of Thymidine Analogue Mutations and Dual-Class Resistance Among HIV-Infected Ugandan Children Failing First-Line Antiretroviral Therapy

Short Communication: High Rates of Thymidine Analogue Mutations and Dual-Class Resistance Among HIV-Infected Ugandan Children Failing First-Line Antiretroviral Therapy

Efficacy and safety of three second-line antiretroviral regimens in HIV-infected patients in Africa

Guidelines for antiretroviral therapy in HIV-1 infected adults and adolescents 2014, Thailand

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