AEGiS-15IAC: Incidence of reverse transcriptase genotypic mutations in children treated with dual nucleoside reverse transcriptase inhibitors: HIV-NAT 013 study.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Incidence of reverse transcriptase genotypic mutations in children treated with dual nucleoside reverse transcriptase inhibitors: HIV-NAT 013 study.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. TuOrB1192)

Ananworanich J, Lolekha R, Pancharoen C, Sirivichayakul S, Siangphoe U, Kaewchana S, Apateerapong W, Mahanontharit A, Chotpitayasunondh T, Ruxrungtham K
Queen Sirikit National Institute of Child Health, Bangkok, Thailand

BACKGROUND: To determine incidence of reverse transcriptase (RT) mutations in Thai children treated with dual NRTI. The results will guide the next appropriate ARV regimen options.

METHODS: Between Mar and May 2003, 100 dual NRTI-treated children attending the pediatric infectious disease clinics at 2 tertiary care centers in Bangkok were recruited. Clinical, HIV RNA, CD4, RT genotyping were performed. Logistic regression analysis was used to determine the association between NRTI regimens and mutations.

RESULTS: Analysis included 95 pts (5 were excluded from other regimens exposure). Data were mean age 6.6 yrs (SD 2.7yrs), Male (41%), CDC class N (2.1%), A (40%), B (51.6%), and C (6.3%), and median CD4 16% (IQR 8-25%) and HIV RNA 4.5 log (IQR 4.1 - 4.5). Mean time on ARV was 3.8 yrs (SD 2.1yrs) with 73.7%, 21% and 5.3% on their 1st, 2nd and 3rd dual NRTI regimens respectively. Current regimens were AZT/ddI (68.4%), AZT/3TC (18.9%), d4T/ddI (6.3%) and d4T/3TC (5.3%). RT mutations to at least 1 NRTI were seen in 92/95 (96.8%) with mutations to AZT in 90.5%, d4T in 90.5%, 3TC in 31.6% and Q151M cpx in 2.1%. Nucleoside analog mutations (NAMS) were seen in 89.5% with 40% having at least 4 NAMS. Top five RT mutations were all NAMS: D67N (58.7%), M41L (43.5%), T215Y (40.2%), K70R (39.1%) and T215F (32.6%). There was 99% AZT-d4T cross-resistance. AZT-based had more NAMS than d4T-based regimens (OR 4.8, p 0.05). NRTI resistance incidence positively correlated with HIV RNA copies. Most parents (96%) said their child did not miss any doses in the past 3 days.

CONCLUSIONS: Almost all children on dual NRTI had RT mutations to at least one NRTI with half having 4 NAMS or more signifying multi-NRTI resistance. Cross-resistance between d4T and AZT was universal. Use of dual NRTI in children should be discouraged. Salvage therapy with 2 new NRTI plus one new class, especially NNRTI, will likely fail in most children.

Keywords: AEGIS, RNA-Directed DNA Polymerase, HIV, Acquired Immunodeficiency Syndrome, HIV Seropositivity, Stavudine, Zidovudine, Incidence, Didanosine, Lamivudine, Anti-HIV Agents, HIV Infections, HIV-1, Mutation, HIV-2, HIV Protease Inhibitors, Child, Humans, Male, genetics, epidemiology

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TuOrB1192