HIV-1 co-receptor tropism and disease progression in children and young adults with perinatally acquired HIV-1 infection. The HICCUP Study

Foster, Caroline; Kaye, Steve; Smith, Colette; Mackie, Nicola

doi:10.1016/s2055-6640(20)30505-7

Cited by 4 publications

(3 citation statements)

References 21 publications

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“…Regarding the drug activity according to GSS, the overall number (IQR) of active drugs was 22 (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). It is notable that only about 2% (N = 24) of individuals had exhausted their treatment options; as expected all of them harboured MDR strains (18 with resistance to four classes and 6 with resistance to three classes).…”

Section: Evaluation Of Drug Activity By Cumulative Genotypic Suscepti...mentioning

confidence: 85%

“…In particular, a significant predominance of X4/dual-mixed strains with FPR 5% was found among perinatally infected individuals, as previously reported in other studies. [12][13][14][15] For these individuals, this association could be explained by the long treatment history and the possible tropism switch either as a result of the CCR5-antagonist use or viral evolution in the course of their HIV infection. 31,[33][34][35][36] Moreover, the proportion of X4/dual-mixed strains with low FPR was significantly higher in patients who were previously exposed to enfuvirtide; this can be explained by the fact that these individuals showed a longer therapeutic history and lower CD4 counts (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…To date, the association of viral tropism with immunological parameters and perinatal HIV transmission among failing patients is well documented. [12][13][14][15][16][17][18] However, most of these studies had a limited sample size and more recent data might be also useful. Moreover, in cART-failing patients, resistance to three or more drug classes is low but still constantly present, therefore they have limited treatment options.…”

Section: Introductionmentioning

confidence: 99%

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Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease

Bouba

Armenia

Forbici

et al. 2021

Journal of Antimicrobial Chemotherapy

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Objectives To evaluate HIV-1 tropism in 1382 combined antiretroviral therapy (cART)-experienced patients failing therapy to characterize those with exhausted therapeutic options. Methods HIV-1 genotypic tropism was inferred through Geno2Pheno by estimating the false-positive-rate (FPR) values. Cumulative resistance and drug activity were evaluated by Stanford algorithm. Results Overall, median (IQR) CD4 count (cells/mm3) nadir and at last genotypic resistance test (GRT) available were 98 (33–211) and 312 (155–517), respectively. Considering HIV-1 tropism, 30.5% had X4/dual-mixed strains (FPR ≤5%: 22.2%; FPR 5%–10%: 8.3%). By stratifying according to tropism, by decreasing FPR, a significant decrease of CD4 nadir and at last GRT was observed. The proportion of individuals with CD4 count <200 cells/mm3, who were perinatally infected and with a long treatment history significantly increased as FPR levels decreased. Regarding resistance, 933 (67.5%) individuals accumulated at least one class resistance, with 52.7%, 48.2%, 23.5% and 13.2% of individuals showing resistance to NRTIs, NNRTIs, PIs and INIs; while 23.2%, 27.2%, 14.3% and 2.8% harboured resistance to 1, 2, 3 and 4 classes, respectively. Individuals with FPR ≤5% showed a significantly higher level of resistance to PIs, NRTIs and INIs compared with others. The proportion of individuals harbouring strains susceptible to ≤2 active drugs was only about 2%; nonetheless, this proportion doubled (4.6%) in patients infected with FPR ≤5%. Conclusions Our findings showed that a small proportion of cART failing individuals have limited therapeutic options. However, tropism determination might help to identify people who have accumulated a high level of resistance and have a greater risk of advanced disease.

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Section: Evaluation Of Drug Activity By Cumulative Genotypic Suscepti...mentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease

Bouba

Armenia

Forbici

et al. 2021

Journal of Antimicrobial Chemotherapy

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Next-generation sequencing provides an added value in determining drug resistance and viral tropism in Cameroonian HIV-1 vertically infected children

Fokam

Bellocchi

Armenia³

et al. 2018

Medicine

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With limited and low-genetic barrier drugs used for the prevention of mother-to-child transmission (PMTCT) of HIV in sub-Saharan Africa, vertically transmitted HIV-1 drug-resistance (HIVDR) is concerning and might prompt optimal pediatric strategies.The aim of this study was to ascertain HIVDR and viral-tropism in majority and minority populations among Cameroonian vertically infected children.A comparative analysis among 18 HIV-infected children (7 from PMTCT-exposed mothers and 11 from mothers without PMTCT-exposure) was performed. HIVDR and HIV-1 co-receptor usage was evaluated by analyzing sequences obtained by both Sanger sequencing and ultra-deep 454-pyrosequencing (UDPS), set at 1% threshold.Overall, median (interquartile range) age, viremia, and CD4 count were 6 (4–10) years, 5.5 (4.9–6.0) log10 copies/mL, and 526 (282–645) cells/mm3, respectively. All children had wild-type viruses through both Sanger sequencing and UDPS, except for 1 PMTCT-exposed infant harboring minority K103N (8.31%), born to a mother exposed to AZT+3TC+NVP. X4-tropic viruses were found in 5 of 15 (33.3%) children (including 2 cases detected only by UDPS). Rate of X4-tropic viruses was 0% (0/6) below 5 years (also as minority species), and became relatively high above 5 years (55.6% [5/9], P = .040. X4-tropic viruses were higher with CD4 ≤15% (4/9 [44.4%]) versus CD4 >15% (1/6 [16.7%], P = .580); similarly for CD4 ≤200 (3/4 [75%]) versus CD4 >200 (2/11 [18.2%] cells/mm3, P = .077.NGS has the ability of excluding NRTI- and NNRTI-mutations as minority species in all but 1 children, thus supporting the safe use of these drug-classes in those without such mutations, henceforth sparing ritonavir-boosted protease inhibitors or integrase inhibitors for the few remaining cases. In children under five years, X4-tropic variants would be rare, suggesting vertical-transmission with CCR5-tropic viruses and possible maraviroc usage at younger ages.

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Changes in cerebral function parameters with maraviroc-intensified antiretroviral therapy in treatment naive HIV-positive individuals

Mora-Peris

Bouliotis

Kulasegaram

et al. 2018

Aids

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HIV-1 co-receptor tropism and disease progression in children and young adults with perinatally acquired HIV-1 infection. The HICCUP Study

Cited by 4 publications

References 21 publications

Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease

Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease

Next-generation sequencing provides an added value in determining drug resistance and viral tropism in Cameroonian HIV-1 vertically infected children

Changes in cerebral function parameters with maraviroc-intensified antiretroviral therapy in treatment naive HIV-positive individuals

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