Resistance to nevirapine differs by HIV-1 subtype

Among pregnant women infected with HIV-1 who receive nevirapine prophylaxis, drug resistance appears to vary depending on virus subtype, according to a report in the Journal of Infectious Diseases for October 1.

Dr. Susan H. Eshleman, from Johns Hopkins Medical Institutions in Baltimore, Maryland, and colleagues studied 102 Ugandan women who were given a single dose of nevirapine as part of the HIV Network for Prevention Trials (HIVNET) 012 study. Thirty-two of these women had children who became HIV-1-positive by 6 to 8 weeks of age, while 70 had infants who did not become infected.

Fifty women had HIV-1 subtype A, 35 had subtype D, 4 had subtype C, 12 had recombination between subtypes, and one woman’s subtype was not classified, the investigators report.

They found that the rate of mother-to-child transmission of HIV-1 did not differ significantly between women with subtype A and those with subtype D. However, at 6 to 8 weeks postpartum, nevirapine resistance mutations were more frequent in women with subtype D than in those with subtype A (adjusted odds ratio 4.94).

The higher rate of nevirapine resistance was not associated with more advanced disease status. “Currently, no evidence exists that nevirapine resistance influences clinical progression of HIV-1 infection, ” Dr. Eshleman and colleagues comment. They do note that “a higher rate of nevirapine resistance in women with subtype D HIV-1 could reflect a higher replication rate of subtype D HIV-1, ” among other differences.

They suggest that pending further investigation, “the potential selection of nevirapine resistance in women receiving the HIVNET 012 regimen must be balanced against the simplicity, efficacy, and cost-effectiveness of the regimen.”

Comment

The previous article (African patients with non-B subtypes respond to HAART) presents evidence that non-clade B infections appear to respond as well as clade B to both PI and NNRTI based regimens. This study suggests, however, that the various sub-types may offer differing pathways to the development of resistance to a single dose of nevirapine monotherapy. This may not, however, translate to higher rates of nevirapine resistance in subtype D infections in the face of longer-term multidrug combination therapy.

Eshleman SH et al. Impact of human immunodeficiency virus type 1 (HIV-1) subtype on women receiving single-dose nevirapine prophylaxis to prevent HIV-1 vertical transmission (HIV network for prevention trials 012 study). J Infect Dis 2001 Oct 1;184(7):914-7.
http://www.ncbi.nlm.nih.gov/pubmed/11509999?dopt=Abstract