Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings

Bartlett, John A.; Ribaudo, Heather J.; Wallis, Carole L.; Aga, Evgenia; Katzenstein, David; Stevens, Wendy; Norton, Michael; Klingman, Karin L.; Hosseinipour, Mina C.; Crump, John A.; Supparatpinyo, Khuanchai; Badal-Faesen, Sharlaa; Kallungal, Beatrice; Kumarasamy, Nagalingeswaran

doi:10.1097/qad.0b013e328353b066

Cited by 41 publications

(30 citation statements)

References 25 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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“…Several previous, noncomparative studies and one small, randomized study have suggested that protease-inhibitor monotherapy may be promising for second-line therapy in resource-limited settings. [26][27][28] The other small 48-week comparative trial in Thailand showed that protease-inhibitor monotherapy was inferior to protease-inhibitor therapy plus NRTIs on the basis of lower rates of viral-load suppression to a level under 50 copies per milliliter (with only a trend toward lower rates of suppression to a level under 400 copies per milliliter and little protease-inhibitor resistance). 29 Since outcomes with protease-inhibitor monotherapy are better when treatment is initiated after viral-load suppression, 6,30,31 we used an induction approach with raltegravir.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Second-Line Antiretroviral Regimens for HIV Therapy in Africa

Paton

Kityo

Hoppé³

et al. 2014

N Engl J Med

183

182

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“…7 Furthermore, very little of the currently available literature describes second-line ART outcomes in HIV-infected patients in Asia. 6, 8-10 …”

Section: Introductionmentioning

confidence: 99%

Efficacy of Second-Line Antiretroviral Therapy Among People Living With HIV/AIDS in Asia

Boettiger¹,

Durier³

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Roughly 4% of the 1.25 million patients on antiretroviral therapy (ART) in Asia are using second-line therapy. To maximize patient benefit and regional resources it is important to optimize the timing of second-line ART initiation and use the most effective compounds available. Methods HIV positive patients enrolled in the TREAT Asia HIV Observational Database who had used second-line ART for ≥6 months were included. ART use and rates and predictors of second-line treatment failure were evaluated. Results There were 302 eligible patients. Most were male (76.5%) and exposed to HIV via heterosexual contact (71.5%). Median age at second-line initiation was 39.2 years, median CD4 cell count was 146 cells/mm3, and median HIV viral load was 16,224 copies/mL. Patients started second-line ART before 2007 (n=105), 2007-2010 (n=147) and after 2010 (n=50). Ritonavir-boosted lopinavir and atazanavir accounted for the majority of protease inhibitor use after 2006. Median follow-up time on second-line was 2.3 years. The rates of treatment failure and mortality per 100 patient/years were 8.8 (95%CI 7.1 to 10.9) and 1.1 (95%CI 0.6 to 1.9), respectively. Older age, high baseline viral load and use of a protease inhibitor other than lopinavir or atazanavir were associated with a significantly shorter time to second-line failure. Conclusions Increased access to viral load monitoring to facilitate early detection of first-line ART failure and subsequent treatment switch is important for maximizing the durability of second-line therapy in Asia. Although second-line ART is highly effective in the region, the reported rate of failure emphasizes the need for third-line ART in a small portion of patients.

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Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings

Cited by 41 publications

References 25 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

Assessment of Second-Line Antiretroviral Regimens for HIV Therapy in Africa

Efficacy of Second-Line Antiretroviral Therapy Among People Living With HIV/AIDS in Asia

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