Frequent nevirapine resistance in infants infected by HIV-1 via breastfeeding while on nevirapine prophylaxis

Abstract

Objective Assess nevirapine (NVP) resistance in infants who became infected in the three arms of the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study: daily infant NVP prophylaxis, triple maternal antiretrovirals (ARV), or no extra intervention for 28 weeks of breastfeeding. Design Prospective cohort study. Methods The latest available plasma or dried blood spot specimen was tested from infants who became HIV-positive between 3 and 48 weeks of age. Population sequencing was used to detect mutations associated with reverse transcriptase inhibitor resistance. Sequences were obtained from 22/25 transmissions in the infant-NVP arm, 23/30 transmissions in the maternal-ARV arm, and 33/38 transmissions in the control arm. Results HIV-infected infants in the infant-NVP arm were significantly more likely to have NVP resistance than infected infants in the other two arms of the trial, especially during breastfeeding through 28 weeks of age (56% in infant-NVP arm vs. 6% in maternal-ARV arm and 11% in control arm, p=0.004). There was a nonsignificant trend suggesting infants with NVP resistance tended to be infected earlier and exposed to NVP while infected for a greater duration than infants without resistance. Conclusions Infants on NVP prophylaxis during breastfeeding are at reduced risk of acquiring HIV, but are at increased risk of NVP resistance if they do become infected. These findings point to the need for frequent HIV testing of infants while on NVP prophylaxis, and for availability of antiretroviral regimens excluding NVP for treating infants who become infected while on such a prophylactic regimen.

Persistence of HIV drug resistance among South African children given nevirapine to prevent mother-to-child-transmission

“…The prevalence of NVP-associated mutations in our cohort is within the range of previous studies involving children who had been exposed to single-dose or extended-NVP prophylaxis, 27% [13] to 60% [3,14,15]. However, previous studies of single-dose NVP involved younger children and demonstrated that resistance decayed to clinically insignificant levels in most infants by 12 months [2,3,9–11].…”

Prevention of TB using rifampicin plus isoniazid reduces nevirapine concentrations in HIV-exposed infants

“…28,29 However, nevirapine has a low barrier to the selection of resistance and high proportions of viral resistance have been reported when there is regimen failure resulting in transmission. 30,31 Our data illustrate the potential danger of treating infants receiving nevirapine with rifampicin and underscore the importance of using isoniazid for TB prophylaxis in this population.…”

Pharmacological Therapy of 141 Client-Owned Cats with Feline Infectious Peritonitis with Mutian ® Xraphconn Adenosine Nucleoside Analogue and Prognostic Prediction of Their Clinical Outcomes

“…17 Some previous studies have already revealed that widespread use of preemptive therapy with anti-viral drugs could be generally suspected as ine cient, because certainly increase risk factors of multi-drug resistance and epidemic infections. [18][19][20] As far as considering severity and mortality rates for FIP at onset, potential epidemic of multi-drug resistant strains must be a great threat for us. Therefore, we are highly con dent that Mutian X should be administered selectively to the FIP subjects possible to get certain therapeutic effects, leading to a variety of bene ts on the cats and their owners.…”