[pronut-hiv] ICAAC: Nevirapine still present in breastmilk two weeks after last dose

["ProNut-HIV" <pronut-hiv@healthnet.org>]

>From Aidsmap

Nevirapine (Viramune) can persist in the breastmilk of HIV-positive
women treated with the drug to prevent mother-to-child transmission of
HIV for up to 14 days after the last dose of the drug is taken,
according to a United States study presented to the 45th Interscience
Conference on Antimicrobial Agents and Chemotherapy in Washington DC.
The investigators, from Alabama and Los Angeles believe "the
persistence of nevirapine in breastmilk may have clinical implications
for the development of resistance in women and infants." 

Mother-to-child transmission of HIV can occur during pregnancy, labour
and via breast-feeding. The non-nucleoside reverse transcriptase
analogue (NNRTI) nevirapine has been shown to be highly effective at
preventing mother-to-child transmission of HIV when provided to the
mother during labour and her infant shortly after. However, the use of
nevirapine in this way can lead to the development of resistance to
nevirapine and other drugs in the NNRTI class of antiretrovirals. In
countries with ready access to anti-HIV therapy, nevirapine monotherapy
to prevent vertical transmission of HIV is strongly cautioned against.
Nevertheless, its use in resource-limited settings is widespread and
recommended. 

Nevirapine readily enters breastmilk at high concentrations.
Investigators wished to see how long nevirapine persisted in breastmilk
after its use was discontinued. 

Samples of breastmilk were collected from the right and left breasts of
an HIV-positive woman seven days after she took her last 200mg dose of
nevirapine. Additional breastmilk samples were taken from the left
breast for a further 15 days. 

The investigators then analysed the breastmilk for the presence of
nevirapine. They wished to determine the maximum concentration of the
drug, the drug's minimum concentration, the elimination half-life, the
area under the curve and clearance of the drug. 

Seven days after the last dose of nevirapine, the concentration of the
drug was 1.56mg/l in the right breast and 1.49mg/l in the left breast.
The last measurable concentration of nevirapine was 14 days after the
last dose, and was 0.17mg/l. 

The maximum concentrations of the drug were 2.67mg/l for the right
breast and 2.78mg/l for the left. The elimination half-life was 40 hours
for both the right and left breasts. The area under the curve was
152mgxh/l for the right breast and 153mgxh/l for the left. 

Apparent clearance of the drug was similar for both breasts at
approximately 2.4 litres per hour. 

The extended analysis of the breast milk from the left breast showed
that it had an area under the curve of 162mgxh/l. The median estimated
area under the curve for both breasts was 57mgxh/l and median 24-hour
clearance was 2.1mg/l. 

"This is the first evaluation of nevirapine pharmacokinetics in
breastmilk to examine the persistence of nevirapine concentrations in
both breasts after treatment discontinuation", note the investigators.
They conclude that their findings of persistence of the drug may have
clinical implications for both the mother and her infant. 

Reference 

Bennetto CJ et al. Persistence of nevirapine concentrations in breast
milk. 45th Interscience Conference on Antimicrobial Agents and
Chemotherapy, New Orleans, abstract H-1905, 2005.