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Triple-Class Failure Rate Higher With Perinatal vs Sexual Infection

Author: Mark Mascolini


08 July 2013

Perinatally HIV-infected youngsters had a higher triple-class failure rate than adolescents and young adults infected heterosexually in a 6045-person analysis of the PLATO II Project of COHERE. Perinatally infected children 10 to 14 years old had a higher risk of triple-class failure if they were born in Europe than Africa.

PLATO II investigators defined virologic failure as a viral load above 500 copies/mL despite 4 months of continuous antiretroviral therapy (ART). They defined triple-class failure as failure of two or more nucleosides, one nonnucleoside, and one ritonavir-boosted protease inhibitor. Because perinatally infected children may have to take antiretrovirals for life, triple-class failure would greatly limit treatment options as these children age.

The study involved 6045 adolescents and young adults, 879 (15%) who became infected with HIV perinatally and 5166 who acquired HIV heterosexually between the ages of 15 and 29. The researchers divided the perinatal group into children who started ART under the age of 2 years, between 2 and 4 years, between 5 and 9 years, between 10 and 14 years, and between 15 and 19 years. 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 PLATO II team divided the heterosexually infected group into those who began ART between the ages of 15 and 19, between the ages of 20 and 24, and 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%.

The investigators identified triple-class failure in 74 children (8.4%) with perinatally acquired HIV and in 182 young adults (3.5%) with heterosexually acquired HIV. Perinatally infected youngsters who began ART between the ages of 10 to 19 had a particularly high rate of triple-class failure. In the 10-to-14-year-old group, the researchers identified 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 investigators noted that European children in the 10-to-14 group "had been diagnosed for some time before starting ART."

Multivariate analysis determined that—across all ages groups—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). Compared with 25-to-29-year-old heterosexually infected people, four groups had an independently higher risk of triple-class failure:

— 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

Study participants who had AIDS before they began ART had a 50% higher risk of triple-class failure (HR 1.5, 95% CI 1.1 to 2.1, P = 0.005), and young people 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."

Source: Diana Gibb, 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.

For the study abstract