T-20 helps to prevent mother-to-child transmission of HIV in women with multi-drug resistant HIV

Treating HIV-positive women with drug-resistant HIV with an antiretroviral regimen containing the fusion inhibitor T-20 (enfurvitide, Fuzeon) can prevent mother-to-child transmission of HIV, according to two case reports from London published in the January 9^th edition of AIDS. In both cases the women had resistance to multiple HIV drugs and took T-20 along with an optimised regimen of anti-HIV drugs to which they were still sensitive.

The investigators noted that T-20 did not cross the placenta and therefore did not cause any side-effects in the newborn babies. Moreover, T-20 has poor penetration into the genital tract and the investigators emphasise that women who need to include T-20 in a treatment regimen to prevent mother-to-child transmission of HIV must have a caesarean section.

Surveillance data from the United Kingdom show that the increased use of anti-HIV therapy has led to an increase in the number of patients with resistance to antiretrovirals. Resistance can also emerge with the use of antiretrovirals during pregnancy. This resistance can be transmitted from a mother to her baby during pregnancy, delivery or breastfeeding.

As HIV prevalence increases in the UK it is anticipated that there will be more pregnancies involving women with drug- resistant HIV meaning that traditional treatment strategies may not be effective.

Doctors at St George’s Hospital in Tooting, south London described two cases where mother-to-child transmission of HIV was prevented by including T-20 in the anti-HIV treatment regimens of pregnant women with multi-drug resistant HIV.

The first case involved a 36 year-old woman who came to the doctors’ attention during week 16 of her pregnancy. She had had two previous babies who had died of AIDS in infancy. Previous HIV treatment had been extensive and had included drugs from all the main classes of antiretrovirals. Her CD4 cell count was 98 cells/mm³ and her viral load was 20,000 copies/ml. Resistance tests revealed the presence of multiple major resistance mutations and the woman was provided with an anti-HIV treatment regimen consisting of abacavir (Ziagen), delavirdine, fosamprenavir (Telzir) and atazanavir (Reyataz).

Viral load initially fell to undetectable, but by week 32 of pregnancy had rebounded to 1,362 copies/ml. Although the risk of mother-to-child transmission was thought to be low, the investigators decided to add T-20 into her regimen and she had a caesarean section during the 39^th weeks of pregnancy. At this time her viral load was undetectable and her CD4 cell count had increased to almost 200 cells/mm³. The infant was treated with an optimised prophylactic regimen consisting of 3TC (lamivudine, Epivir) and Kaletra. Over the next four months four separate viral load tests showed that the baby was not infected with HIV and it did not experience any ill effects due to either its mother’s or its own anti-HIV therapy.

The second case involved a 33 year-old woman who came to the doctors’ attention during the sixth week of her pregnancy. Her CD4 cell count at this time was 75 cells/mm³ and her viral load was 20,000 copies/ml. In the past she had received treatment with drugs from all the main classes of antiretrovirals and had multiple resistance mutations.

An optimised antiretroviral regimen of 3TC, nevirapine, tenofovir, ritonavir and fosamprenavir was started, but by week 32 her CD4 cell count had fallen to 51 cells/mm³ and her viral load had increased to 31,000 copies/ml. Problems with adherence were reported and the woman was admitted to hospital and provided with directly observed therapy. At this time T-20 was also added to her regimen.

After two weeks of this treatment, when her viral load was 305 copies/ml and her CD4 cell count 135 cells/mm³, she had a caesarean section. The baby was once again treated with 3TC and Kaletra and was not infected with HIV.

“Our data indicate that [T-20] may play a role as an adjunct in preventing mother-to-child transmission of multi-drug resistant HIV”, write the investigators.

The investigators believe that the drug helped prevent transmission by lowering maternal blood levels of HIV. They note that T-20 has poor penetration into the genital tract and that women who need to take the drug to prevent transmission of HIV to their infants should have a caesarean section.