- Category: HIV Treatment
- Published on Friday, 16 November 2012 00:00
- Written by Liz Highleyman
Babies who started taking lopinavir-based antiretroviral therapy (ART) soon after they were diagnosed with HIV experienced good virological response that was sustained through 6 years, even after they stopped treatment, according to long-term data from the CHER study presented at the 11th International Congress on Drug Therapy in HIV Infection (HIV11) this week in Glasgow.
Avy Violari from University of the Witwatersrand in Johannesburg and fellow investigators with the CHER (Children with HIV Early Antiretroviral Therapy) study looked at virological outcomes and drug resistance among South African children using different HIV treatment strategies. Infants who initiated protease inhibitor-based therapy immediately after HIV diagnosis but stayed on treatment for a limited period (early limited ART) were compared against babies who delayed treatment until they showed signs of immune system decline but then stayed on continuous therapy (deferred continuous ART).
All babies in this randomized controlled study were treated with lopinavir/ritonavir (Kaletra) plus zidovudine (AZT; Retrovir) and lamivudine (3TC; Epivir). Two-thirds started immediately upon diagnosis, while one-third waited until they experienced clinical or immunological HIV disease progression. Infants undergoing immediate ART were assigned to interrupt treatment after either 40 or 96 weeks, resuming if they experienced clinical or immunological progression.
The researchers enrolled a total of 377 infants; when the study was halted in June 2011, 353 had started combination ART. As previously reported, the primary study finding was that early treatment was superior to deferred ART, lowering the risk of disease progression and death.
- The median age at ART initiation was about 4 weeks in the immediate 40-week arm and nearly 8 weeks in the immediate 96-week arm, compared with 26 weeks in the deferred treatment arm.
- However, all children regardless of randomized treatment assignment ended up staying on therapy for a similar duration, about 240 weeks.
- 87% of babies in the deferred ART arm achieved HIV suppression < 400 copies/mL, compared with 84% in the immediate 40-week ART arm and 83% in the immediate 96-week arm (not a significant difference).
- Among the children with viral load > 1000 copies/mL who underwent resistance testing, 41% had evidence of resistance mutations:
o 7 with M184V mutations, which confers resistance to lamivudine;
o 2 with major protease inhibitor resistance mutations (V82A/L76V);
o 2 with major NNRTI resistance mutations (K103N/M230L).
Based on these findings, the CHER researchers concluded, "Virological response on ART was excellent in this large cohort of infants initiating [lopinavir/ritonavir/zidovudine/lamivudine] at a very young age, with no differences between randomized strategies, suggesting that planned interruption after early limited ART does not adversely affect virological outcomes."
"Overall, approximately 40% of those on ART with VL > 1000 copies/mL had a resistance mutation; protease inhibitor mutations were infrequent, despite around 5 years on therapy," they added.
Abstracts from the HIV11 Congress are published in a supplement of the Journal of the International AIDS Society, which can be viewed online or downloaded at www.jiasociety.org/index.php/jias/issue/view/1461.
A Violari, M Cotton, K Otwombe, et al. Does early initiation of ART in infants affect virological and resistance outcomes? Data from the CHER trial after 6 years of follow-up. 11th International Congress on Drug Therapy in HIV Infection (HIV11). Glasgow, November 11-15, 2012. Abstract O224.