Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1.
BACKGROUND
Intrapartum single-dose nevirapine decreases mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but promotes nevirapine resistance. Although resistant viruses fade to undetectable levels in plasma, they may persist as stably integrated proviruses within the latent reservoir in resting CD4(+) T cells, potentially complicating future treatment.


METHODS
Blood samples were collected from 60 women from South Africa and Uganda >6 months after they had received single-dose nevirapine. To selectively analyze the stable latent form of HIV-1, resting CD4(+) T cells were isolated and activated in the presence of reverse-transcriptase inhibitors and integrase inhibitors, which allows for the specific isolation of viruses produced by cells with stably integrated proviral DNA. These viruses were then analyzed for nevirapine resistance.


RESULTS
Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), nevirapine resistance mutations (K103N and G190A) were detected in the latent reservoir of 4 (8%) of 50 evaluable women.


CONCLUSIONS
A single dose of nevirapine can establish antiretroviral resistance within the latent reservoir. This results in a potentially lifelong risk of reemergence of nevirapine-resistant virus and highlights the need for strategies to prevent transmission that do not compromise successful future treatment.
Wind-Rotolo
Megan
M
Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. mwrotolo@gmail.com
Durand
Christine
C
Cranmer
Lisa
L
Reid
Alison
A
Martinson
Neil
N
Doherty
Meg
M
Jilek
Benjamin L
BL
Kagaayi
Joseph
J
Kizza
Allan
A
Pillay
Visva
V
Laeyendecker
Oliver
O
Reynolds
Steven J
SJ
Eshleman
Susan H
SH
Lau
Bryan
B
Ray
Stuart C
SC
Siliciano
Janet D
JD
Quinn
Thomas C
TC
Siliciano
Robert F
RF