Emergence of antiretroviral resistance in HIV-positive women receiving combination antiretroviral therapy in pregnancy.
BACKGROUND
Antenatal antiretroviral therapy is integral to preventing vertical transmission of HIV-1. The impact of temporary triple antiretroviral therapy in pregnancy on the emergence of antiretroviral resistance has not been studied.


OBJECTIVE
To determine the impact of temporary triple antiretroviral therapy in pregnancy on emergence of antiretroviral resistance.


METHODS
Pregnant HIV-1 infected women with a pre-treatment CD4 cell count >300 x 10(6)/l initiated triple antiretroviral therapy in the third trimester and discontinued postpartum. Genotypic resistance testing was performed after antiretroviral cessation and on pretreatment samples when postpartum samples showed primary mutations.


RESULTS
In a cohort of 50 women who initiated antiretroviral therapy in pregnancy, 39 (78%) had postpartum HIV-1 nucleotide sequences available for analysis: 35 of these (90%) were previously antiretroviral naive. Seven primary mutations, V106A (one), Y181C (two), G190A (one), K101E (one), M184V (one), T215S (one) were detected in five (13%) women. All five were on regimens that included nevirapine and all were antiretroviral therapy naive prior to the index pregnancy. Four had no mutations detected pretreatment (one did not have a pretreatment analysis available; viral load 83 copies/ml). The median duration of antiretroviral exposure was 70 days.


CONCLUSIONS
Emergence of genotypic resistance is significant in this cohort of pregnant women. All mutations detected were in those that took nevirapine-containing regimens. The clinical implications of these mutations are unknown.
Lyons
Fiona E
FE
Department of Infectious Diseases and Genitourinary Medicine, St James's, Dublin, Ireland. fionalyons69@yahoo.co.uk
Coughlan
Suzie
S
Byrne
Christina M
CM
Hopkins
Susan M
SM
Hall
William W
WW
Mulcahy
Fiona M
FM
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001483:Base Sequence; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D009154:Mutation; D019829:Nevirapine / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011295:Prenatal Care / Q000379:methods; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine