Tenofovir and FTC are antiretroviral drugs that are used worldwide. They both have a long half-life and drug regulatory authorities in the US have categorised them as “probably safe” during pregnancy.
Investigators wished to see if taking a single dose of these two drugs with nevirapine during labour reduced the risks of subsequent maternal NNRTI resistance. In theory, three drugs with similarly long half-lives should suppress viral load for longer, reducing the risk of resistance to nevirapine.
They therefore designed a study involving HIV-positive pregnant women using public sector health facilities in Lusaka, Zambia. The study ran between 2005 and early 2007.
All the women were given a single 200mg dose of nevirapine to take home. They were instructed to take this dose at the onset of labour. None of the women recruited to the study qualified for antiretroviral therapy under WHO antiretroviral treatment guidelines. However, as per the WHO HIV pregnancy guidelines, the women were given AZT which they were instructed to start taking during the 32nd week of pregnancy.
Half the women were then randomised to receive a single dose of oral tenofovir (300mg) and FTC (200mg) during labour.
Blood samples were obtained from the women two and six weeks after labour to test for the presence of drug resistance.
Testing of umbilical cord blood samples showed that 315 (82%) of women took their single-dose nevirapine. The proportion of women taking the drug did not differ between the treatment and control arm. The women who were randomised to take tenofovir/FTC took this treatment a mean of 3.5 hours before delivery.
Women who received tenofovir and FTC had a lower viral load two weeks after delivery. The investigators found that 63% of women who received these drugs had a viral load below 400 copies/ml compared to 53% of women in the control arm, a statistically significant difference (p = 0.043). Furthermore, amongst the women with detectable viral load at week two, it was lower in those who received tenofovir and FTC (mean 2500 copies/ml vs. 6300 copies/ml, p = 0.004).
Women who received tenofovir and FTC were much less likely to have NNRTI-resistant virus present at week two (RR, 0.27; 95% CI, 0 – 0.66) and week six (RR, 0.47; 95% CI, 0.29 – 0.76).
When the investigators analysed their results according to maternal viral load at the time of delivery, they found that the addition of tenofovir and FTC had the greatest benefit in terms of preventing NNRTI resistance for women whose viral load was 10,000 copies/ml or above (week two, p = 0.001; week six, p = 0.003).
NNRTI resistance mutations were found in 14% of women in the control arm, but just 3% of women in the tenofovir/FTC arm. No tenofovir, FTC or AZT resistance was detected.
The rate of mother-to-child transmission of HIV was 6% in the tenofovir/FTC arm and 8% in the control arm, a non-significant difference. Most of these transmissions occurred in the womb before AZT therapy was started.
No side-effects attributable to tenofovir or FTC were observed in either the mothers or their infants at weeks two and six. Creatinine, liver function and haemoglobin were comparable between the treatment and control arms.
“Addition of a single dose of combined tenofovir and emtricitabine to the antiretroviral prophylaxis regimen of short-course zidovudine and nevirapine effectively reduced the frequency of postpartum resistance to non-nucleoside reverse transcriptase inhibitors”, write the investigators.
The accompanying editorial is generally enthusiastic about the findings of the study. But it does point out that a number of questions about the safety and efficacy of this strategy remain unanswered. These include the risk of resistance for women with low viral loads (under 2000 copies/ml) and the risk of not only nevirapine but also tenofovir and FTC resistance for infants.
The authors of the editorial also question the circumstances in which tenofovir and FTC in addition to nevirapine might be used. They note, “combination three-drug prophylaxis might in the future be increasingly available to all pregnant HIV-1-infected women regardless of CD4 cell count, which would make single-dose nevirapine obsolete.”
Nevertheless they conclude that the study shows “that addition of single-dose tenofovir/emtricitabine to short-course [AZT] and single-dose nevirapine…is effective and feasible”.