Multi-drug resistance in vertically infected children
Polly Clayden, HIV i-Base
Vertically infected children are now surviving to adolescence and adulthood; in the CHIPS cohort the median age is now approaching 10 years.
A poster from St Marys Hospital and Chelsea and Westminster Hospital family clinics evaluated the prevalence of triple class genotypic resistance and clinical outcome in a paediatric cohort between 1 November 2005 and 31 October 2006, in a retrospective case note review.
This cohort has 220 HIV positive children with a median age 9.9 years (range 0.4-17.7 years), 47% male, 80% Black African. 179 (81%) had ever received antiretroviral therapy: 4 NRTIs alone; 91 had received 2 classes and 84 had received 3 classes of ART. At latest follow up 156 children were on HAART and 127 (81%) had viral loads of <50 copies/mL and median CD4%, 35% (IQR 29-40%).
95/214 children (44%) had ever had a resistance test including 11 who had baseline resistance testing prior to initiation of therapy and all had wild type virus. Of the 84 children having had resistance testing after initiation of therapy 32 (38%) had wild type virus, 31 (37%) had M184I/V mutations and 46 (55%) had non M184V mutations most frequently thymidine-associated mutations, 52 (62%) had NNRTI-associated mutations, most commonly 181C/I and 11 children had major protease mutations.
Of the 179 children who had ever received ART, 34 (19%) had dual class and 6 (3%) had triple class resistance, 2 of whom died during the study.
Of the multi drug resistant children 4/6 children were male, all of black African origin, born between 1988 and 2000 with 3.9-14.9 years on ART and 5/6 had received mono/dual ART prior to HAART. Median number of drugs ever received 13 (range 9-14) and 3 had received T20. Two children died during the study period. Of the remaining children, at latest follow up, all have detectable viral load (range 587 to >500,000 copies/mL) half have a CD4 count of 0 cells/mm3 (range 0-450 cells/mm3).
One patient was receiving 3TC alone; one abacavir+tenofovir+lopinavir/r; one tenofovir+FTC+abacavir+T20+TMC114/r and one tenofovir+FTC+ddI+tipranavir/r (T20 was stopped).
The investigators wrote: Perinatally infected children with MDR HIV living in the UK urgently require access to novel salvage therapies if they are to survive.
Although these data are depressing this is a small snapshot from a cohort historically treated with suboptimal regimens, lack of options and evidence. Hopefully the future is brighter for kids starting therapy now. CHIPS is now looking at resistance across the whole cohort.
Many questions are arising, now that children with HIV are living much longer, around how to stop kids getting resistance by adolescence so that they can start their adult life well with treatment options.
However this experience from London is replicated across western Europe and north America and for this group of young people novel salvage therapies are a priority. In this regard there was a poster at this conference documenting a case study of using TMC114 and T20 in a heavily treated 12 year old (Bamford et al). PK data revealed the need for three times a day dosing with TMC 114. Tibotec is undertaking a PK study of TMC114 in children and the results will be ready in January 2007.
Foster C, Mackie N, Seery P et al. Emerging multi-drug resistance in children with perinatally acquired HIV-1. 8th International Congress on Drug Therapy in HIV Infection, 12-16 November 2006, Glasgow. Poster abstract P 360.