Boosted protease inhibitors as a therapeutic option in the treatment of HIV‐infected children

Ramos, JT

doi:10.1111/j.1468-1293.2009.00728.x

Cited by 9 publications

(10 citation statements)

References 48 publications

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“…The impact of DRMs acquired via prevention of mother-to-child transmission could not be evaluated in our study, but we previously reported a moderate (between 5% and 15%) prevalence of DRMs in the Central African HIV-infected pediatric population of Bangui. [96] These observations support the use of lopinavir-based 1st-line regimens in children in Africa as recommended by the WHO, [7,8,46,82,85,90,97] especially with the recent national recommendations to implement lifelong antiretroviral treatment for mothers. However, only 1 (12.5%) of the 8 children aged below 5 years was on a 1st-line PI-based antiretroviral treatment regimen in 2013 as recommended by the WHO, illustrating that these guidelines have not yet been implemented.…”

Section: Discussionsupporting

confidence: 59%

High levels of virological failure with major genotypic resistance mutations in HIV-1-infected children after 5 years of care according to WHO-recommended 1st-line and 2nd-line antiretroviral regimens in the Central African Republic

et al. 2017

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A large cohort of 220 HIV-1-infected children (median [range] age: 12 [4–17] years) was cared and followed up in the Central African Republic, including 198 in 1st-line and 22 in 2nd-line antiretroviral regimens. Patients were monitored clinically and biologically for HIV-1 RNA load and drug resistance mutations (DRMs) genotyping. A total of 87 (40%) study children were virological responders and 133 (60%) nonresponders. In children with detectable viral load, the majority (129; 97%) represented a virological failure. In children receiving 1st-line regimens in virological failure for whom genotypic resistance test was available, 45% displayed viruses harboring at least 1 DRM to NNRTI or NRTI, and 26% showed at least 1 major DRM to NNRTI or NRTI; more than half of children in 1st-line regimens were resistant to 1st-generation NNRTI and 24% of the children in 1st-line regimens had a major DRMs to PI. Virological failure and selection of DRMs were both associated with poor adherence. These observations demonstrate high rate of virological failure after 3 to 5 years of 1st-line or 2nd-line antiretroviral treatment, which is generally associated with DRMs and therapeutic failure. Overall, more than half (55%) of children receiving 1st-line antiretroviral treatment for a median of 3.4 years showed virological failure and antiretroviral-resistance and thus eligible to 2nd-line treatment. Furthermore, two-third (64%) of children under 2nd-line therapy were eligible to 3rd-line regimen. Taken together, these observations point the necessity to monitor antiretroviral-treated children by plasma HIV-1 RNA load to diagnose as early as possible the therapeutic failure and operate switch to a new therapeutic line.

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Section: Discussionsupporting

confidence: 59%

High levels of virological failure with major genotypic resistance mutations in HIV-1-infected children after 5 years of care according to WHO-recommended 1st-line and 2nd-line antiretroviral regimens in the Central African Republic

et al. 2017

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“…7,[11][12][13][14]20,[25][26][27][28][29][30] Furthermore, the rate of therapeutic failure appears greater when NNRTI-based regimens are used as a first-line treatment, and then ranges from 20% to 75%, 7,[11][12][13][14]20,25,28,29 compared to when a PI-based regimen is used (range: 26-36%). 26,27 In the series of children reported here, who were prescribed mostly with a first-line ARV treatment, including NNRTI, virological failure was frequently associated with major NNRTI-resistance mutations, whereas no major PI-resistance mutations were observed in children treated by firstline PI therapy.…”

Section: Discussionmentioning

confidence: 96%

“…These observations emphasize the possibility of using PI more frequently as a pediatric first-line regimen in Africa. 20,30 In particular, the use of an LPV-based treatment could be of interest because of the frequent transmitted drug resistance to NNRTI caused by the common use of single-dose NVP to prevent HIV mother-to-child transmission in subSaharan Africa. In addition, there is a higher rate of virological success in PI-treated children versus NNRTI-treated children.…”

Section: Discussionmentioning

confidence: 99%

Virological Response and Resistance Profiles After 18 to 30 Months of First- or Second-/Third-Line Antiretroviral Treatment: A Cross-Sectional Evaluation in HIV Type 1-Infected Children Living in the Central African Republic

Charpentier

Gody

Mbitikon

et al. 2012

AIDS Research and Human Retroviruses

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A total of 242 HIV-1-infected children were followed up at the Complexe Pédiatrique of Bangui, Central African Republic, including 165 receiving antiretroviral treatment in first- (n=150) or second-/third-line (n=15) regimens. They were prospectively included in a study, in 2009, to assess their virological status and prevalence of antiretroviral drug-resistance mutations in cases of virological failure, according to revised 2010 WHO criteria (e.g., HIV-1 RNA >3.7 log(10) copies/ml). Detectable plasma HIV-1 RNA was observed in 53% of children under first-line treatment, and virological failure was diagnosed in 40%, which was associated in 85% of cases with viruses harboring at least one drug-resistance mutation to nucleoside reverse transcriptase inhibitors (NRTI) or nonnucleoside reverse transcriptase inhibitors (NNRTI), and in 36% of cases with at least one major drug-resistance mutation to NRTI or NNRTI when excluding the M184V mutation. Overall, the proportion of children receiving a first-line regimen for a median of 18 months with virological failure associated with drug-resistance mutations, and thus eligible for a second-line treatment, was estimated at 34% of the whole cohort. In children under second-/third-line therapy, virological failure occurred in 47%, plus at least one major drug-resistance mutation to NRTI or NNRTI, though less commonly to protease inhibitors. Taken together, these findings argue in favor of the urgent need to improve distribution of pediatric antiretroviral drugs in the Central African Republic, to increase adherence by treated children, and to offer adequate HIV biological monitoring.

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“…Children who started LPVr were switched to a NVP-based regimen after achieving virological suppression. To facilitate dose calculations, we used weight band-based dosing of paediatric LPVr tablets (100 mg/25 mg) to achieve an approximate dose of 300 mg/m 2 /dose (10–20 kg, 2-0-2; 20–30 kg, 3-0-3; >30 kg, 4-0-4) [16], [17]. Paediatric LPVr tablets were substituted by larger adult tablets (200 mg/50 mg) if the child was able to swallow them (in these cases, the dosing in the 20–30 kg band was 2-0-1 adult tablets).…”

Section: Methodsmentioning

confidence: 99%

Induction with Lopinavir-Based Treatment Followed by Switch to Nevirapine-Based Regimen versus Non-Nucleoside Reverse Transcriptase Inhibitors-Based Treatment for First Line Antiretroviral Therapy in HIV Infected Children Three Years and Older

et al. 2014

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BackgroundThe World Health Organization recommends non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based antiretroviral therapy (ART) for children three years and older. In younger children, starting ART with lopinavir boosted with ritonavir (LPVr) results in lower risk of virological failure, but data in children three years and older are scarce, and long-term ART with LPVr is problematic in resource-poor settings.MethodologyRetrospective cohort of children three years and older who started triple ART including LPVr or a NNRTI between 2007 and 2013 in a rural setting in India. Children who started LPVr were switched to nevirapine-based ART after virological suppression. We analysed two outcomes, virological suppression (HIV-RNA <400 copies/ml) within one year of ART using logistic regression, and time to virological failure (HIV-RNA >1000 copies/ml) after virological suppression using Cox proportional hazard regression. A sensitivity analysis was performed using inverse probability of treatment weighting (IPTW) based of propensity score methods.FindingsOf 325 children having a viral load during the first year of ART, 74/83 (89.2%) in the LPVr group achieved virological suppression versus 185/242 (76.5%) in the NNRTI group. In a multivariable analysis, the use of LPVr-based ART was associated with higher probability of virological suppression (adjusted odds ratio 3.19, 95% confidence interval [CI] 1.11–9.13). After IPTW, the estimated risk difference was 12.2% (95% CI, 2.9–21.5). In a multivariable analysis including 292 children who had virological suppression and available viral loads after one year of ART, children switched from LPVr to nevirapine did not have significant higher risk of virological failure (adjusted hazard ratio 1.18, 95% CI 0.36–3.81).ConclusionsIn a cohort of HIV infected children three years and older in a resource-limited setting, an LPVr induction- nevirapine maintenance strategy resulted in more initial virological suppression and similar incidence of virological failure after initial virological suppression than NNRTI-based regimens.

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Boosted protease inhibitors as a therapeutic option in the treatment of HIV‐infected children

Cited by 9 publications

References 48 publications

High levels of virological failure with major genotypic resistance mutations in HIV-1-infected children after 5 years of care according to WHO-recommended 1st-line and 2nd-line antiretroviral regimens in the Central African Republic

High levels of virological failure with major genotypic resistance mutations in HIV-1-infected children after 5 years of care according to WHO-recommended 1st-line and 2nd-line antiretroviral regimens in the Central African Republic

Virological Response and Resistance Profiles After 18 to 30 Months of First- or Second-/Third-Line Antiretroviral Treatment: A Cross-Sectional Evaluation in HIV Type 1-Infected Children Living in the Central African Republic

Induction with Lopinavir-Based Treatment Followed by Switch to Nevirapine-Based Regimen versus Non-Nucleoside Reverse Transcriptase Inhibitors-Based Treatment for First Line Antiretroviral Therapy in HIV Infected Children Three Years and Older

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