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Higher Rate of Triple-Class Failure in Pernitally Infected Than Heterosexually Infected
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7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur
Mark Mascolini
Failure of one or more drugs in the first three antiretroviral classes--triple-class failure--was more common in perinatally infected youngsters than in young people heterosexually infected with HIV after birth, according to results of a 6045-person international review. The study also found that many perinatally infected European youngsters had been diagnosed some time before they started antiretroviral therapy (ART).
Because perinatally infected children may require ART for life, avoiding triple-class failure is critical to preserving antiretroviral options. Previous work by these researchers found an overall 12% risk of triple-class failure in children 5 years after starting ART [2]. That study linked starting ART at an older age to a higher risk of triple-class failure and found a twice higher risk of triple-class failure in children than adults.
In a new study, the PLATO II Project Team of COHERE explored differences in triple-class failure between perinatally infected children and heterosexually infected adults younger than 30. Study participants started ART when antiretroviral naive from 1998 onwards and were either (1) perinatally infected youngsters who started ART before reaching age 20 or (2) heterosexually infected youth and young adults who started ART between the ages of 15 and 29.
The researchers defined virologic failure as a viral load above 500 copies despite 4 months of continuous ART; they defined triple-class failure as virologic failure of two or more nucleosides, one nonnucleoside, and one ritonavir-boosted protease inhibitor. Follow-up continued from the start of ART until the last recorded viral load.
The analysis focused on 6045 people, 879 (15%) who acquired HIV perinatally and 5166 who became infected heterosexually between the ages of 15 and 29. The perinatal group included 238 children (27% of 879) who started ART under the age of 2, 148 (17%) who started between 2 and 4, 230 (26%) who started between 5 and 9, 189 (22%) who started between 10 and 14, and 74 (8%) who started between 15 and 19. Respective proportions of girls in those five groups were 58%, 44%, 48%, 53%, and 69%. Respective proportions of sub-Saharan Africans were 24%, 51%, 67%, 60%, and 28%, and proportions of Europeans were 71%, 41%, 27%, 27%, and 14%.
The heterosexually infected group included 264 (5% of 5166) who began ART between the ages of 15 and 19, 1459 (28%) who began between the ages of 20 and 24, and 3443 (67%) who began between the ages of 25 and 29. Respective proportions of girls in those three groups were 78%, 78%, and 73%, proportions of sub-Saharan Africans were 39%, 31%, and 26%, and proportions of Europeans were 13%, 19%, and 21%.
Triple-class failure occurred in 74 children (8.4%) with perinatally acquired HIV and 182 (3.5%) with heterosexually acquired HIV. Perinatally infected children who started ART at the age of 10 to 19 had a particularly high rate of triple-class failure. In the 10-to-14-year-old group, there was a strong trend toward a higher risk of triple-class failure in European-born children than in African-born children (hazard ratio [HR] 2.1, 95% confidence interval [CI] 0.9 to 5.3). The researchers observed that European children in the 10-to-14 group "had been diagnosed for some time before starting ART."
Across all age groups, however, multivariate analysis determined that European-born children and young adults had a 40% lower risk of triple-class failure than youngsters and young adults from Africa (HR 0.6, 95% CI 0.4 to 0.8, P = 0.007).
Multivariate analysis also figured risk of triple-class failure in every age group compared with 25-to-29-year-old heterosexually infected people. The following groups had independently higher chances of triple-class failure at the following hazard ratios and 95% CIs:
-- Perinatally infected under 2: HR 1.8, 95% CI 1.1 to 3.1
-- Perinatally infected 5 to 9: HR 2.0, 95% CI 1.2 to 3.2
-- Perinatally infected 10 to 14: HR 4.2, 95% CI 2.6 to 6.7
-- Heterosexually infected 20 to 24: HR 1.3, 95% CI 1.0 to 1.8
In the same analysis, study participants who had AIDS before they started ART had a 50% higher risk of triple-class failure (HR 1.5, 95% CI 1.1 to 2.1, P = 0.005). Participants who started ART with a ritonavir-boosted protease inhibitor had a 40% lower risk of triple-class failure than those who started with a nonnucleoside (HR 0.6, 95% CI 0.5 to 0.9, P = 0.006).
The researchers propose that "there may be a beneficial effect of starting ART prior to adolescence, to help attain and sustain virologic suppression before the onset of this often difficult transitional stage of development."
References
1. Gibb DM, on behalf of the PLATO II Project Team of COHERE. Higher rates of triple class virologic failure in perinatally HIV-infected teenagers compared to heterosexually infected young adults in the PLATO II study. 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur. Abstract TUPE311.
2. Pursuing Later Treatment Options II (PLATO II) project team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE), Castro H, Judd A, Gibb DM, et al. Risk of triple-class virological failure in children with HIV: a retrospective cohort study. Lancet. 2011;377:1580-1187. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099443/
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