ARV drugs safe for breastfed infants

0311-1-1-GRAPHRoselyne Sachiti Features Editor —
In most African settings, a large number of women spend most of their reproductive years either pregnant or breastfeeding a child. Exclusively breastfeeding a child for six months has had many positive effects on child development that include developing a child’s IQ.

Not only does breastfeeding have clear short-term benefits, such as protection from infectious diseases and a reduction in mortality, it’s also been shown to be associated with an increase in intelligence.

But, if a woman is pregnant and living with HIV, the woman’s blood could pass into her baby’s body. This is most likely to occur in the last few weeks of pregnancy, during labour, or delivery. Breastfeeding a baby can also transmit HIV, because HIV is found in breast milk of HIV positive mothers. In fact, there is a 15-45 percent chance of passing HIV to a baby if neither the mother or child is on HIV treatment.

With the potential for infant infection if their mother acquires HIV during breastfeeding due to high viremia, researchers like Kenneth Mugwanya from the University on Washington, United States and his team carried out a study which sought to find whether there is infant exposure to Tenofovirand Emtricitabine when used as Pre-exposure Prophylaxis by breastfeeding HIV-uninfected women.

Mugwanya and his fellow researchers spent time studying the safety of breastfeeding mothers who are HIV negative using the antiretroviral tenofovir.

The study results which were released at HIV Research for Prevention (HIVR4P) 2016 in Chicago US recently, provided good news — the infant does not get exposed to the ARV drug taken by the mother. The research was conducted on HIV negative breastfeeding mothers in Kenya and Uganda, to check whether the antiretroviral can be excreted into breast milk and absorbed by the breast feeding infant.

According to Mugwanya’s research findings, 94 percent of infant plasma had no detectable tenofovir levels.

“This data is really important and reassuring especially for us in sub Saharan Africa where young women are at high risk of HIV and a significant number of them spend their lifetime either pregnant or breastfeeding,” Mugwanya told The Herald Review in Chicago.

He said the goal of their research was to determine whether tenofovir and emtricitabine when taken as PrEP by lactating HIV-uninfected women were excreted into human milk and then absorbed by breastfeeding infants in clinically significant concentrations.

A prospective, 10-day, open-label, repeat-dose study among 50 HIV uninfected breastfeeding women and infants 1-24 weeks post-partum, the research was held between January and June 2015.

“Infants breastfed by women using TDF-based PrEP are exposed to minimal TFV and FTC concentration through breastfeeding that is likely to be of limited clinical consequence.

“Tenofovir was unquantifiable in 94 percent of infant plasma samples.

“Based on breast milk concentrations, breastfeeding infants would have exposures to TFV12, 500-fold lower, and to FTC 200-fold lower, than those achieved with pediatric therapeutic dosing,” he added.

He said fathers provided written permission for infants to enrol in the study. In 2015, the World Health Organisation (WHO) recommended PrEP as “an additional prevention choice for people at substantial risk of HIV infection, as part of combination HIV prevention approaches,” defining “substantial risk” as HIV incidence 3 per 100 person-years in the absence of PrEP.

Based on the available data, pregnant and lactating women residing in sub-Saharan Africa clearly meet this definition, according to another researcher Lynne M. Mofenson, of the Elizabeth Glaser Pediatric AIDS Foundation in Washington, DC, US.

However, she said, according to current WHO guidelines, “further research is needed to fully evaluate PrEP use during pregnancy and breastfeeding”.

“The approved drug label for TDF states that the drug “should be used during pregnancy only if clearly needed . . . Because of both the potential for HIV-1 transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving “the drug)” . Thus, there is a critical need to examine the safety of PrEP in HIV-uninfected pregnant and breastfeeding women (particularly adolescent and young women) and their infants.

“The accompanying Research Article by Kenneth Mugwanya and colleagues in PLOS Medicine significantly contributes to the accumulating safety data for PrEP in breastfeeding women,” she said.

She added that the data provided by Mugwanya and colleagues’ study and others were important because sustained high HIV incidence among adolescent and young women in sub-Saharan Africa constituted a significant public health emergency.

“HIV prevalence is 1,7 times higher among young women in sub-Saharan Africa than in young men and eight times higher among females than males aged 15–19 years in South Africa; among adolescents in sub-Saharan Africa, 71 percent of new HIV infections are among females. Pregnancy rates in these young women are also high. Sub-Saharan Africa has the highest prevalence of pregnancy in women aged 15–19 years globally; births to teenage mothers account for more than half of all births, an estimated 101 births per 1,000 women aged 15–19 years,” she added.

She also said being a pregnant or lactating woman in sub-Saharan Africa is associated with a substantial risk of HIV acquisition, and acute HIV infection during pregnancy or lactation is associated with high rates of mother-to child HIV transmission.

Although limited, most data on TDF during pregnancy are from HIV-infected women receiving combination antiretroviral therapy (ART), with the majority of studies in HIV infected women on ART and their infants showing no adverse effects of TDF exposure.

“However, the balance of benefits and risks of using TDF in HIV-infected pregnant women, in whom there is known risk of morbidity and mortality without therapy, differs from use in HIV-uninfected women, in whom the drug is being used for prophylaxis rather than treatment of infection.

“Additionally, because pregnancy outcomes among HIV-infected women, even those receiving ART, are worse than in HIV-uninfected women, comparability of data from the HIV-infected to the uninfected population has limitations and likely provides a worst-case scenario in terms of adverse events.”

She also said TDF has been used for prevention of perinatal hepatitis B virus (HBV) transmission in HBV-infected pregnant women with high concentrations of HBV DNA, for whom the risk of perinatal HBV transmission is high even when the infant receives hepatitis B immunoglobulin and HBV vaccine.

“In these instances, TDF, given as a single drug, is initiated in the third trimester of pregnancy and usually (but not always) stopped 1–2 months postpartum. Studies in HBV mono-infected pregnant women demonstrated adverse event rates much lower than those seen in HIV-infected women, and no significant differences in pregnancy outcomes were observed between TDF and no drug exposure,” she added.

She also said TDF and TDF/FTC have been evaluated in oral PrEP randomised, controlled clinical trials that included non-pregnant women of child-bearing age, in which pregnancies have occurred in women receiving PrEP at the time of conception.

“Two of these trials have reported on pregnancy outcomes in such women, reporting no difference in adverse pregnancy outcomes between active and placebo arms. However, in these trials, PrEP was discontinued after pregnancy was recognized, and, in the VOICE trial, adherence to PrEP was suboptimal,” she added.

Given that young women, particularly if pregnant or breastfeeding, in sub-Saharan Africa experience some of the highest incidence rates of HIV infection globally, the benefits of HIV prevention in pregnant and breastfeeding women and their infants in these regions, given the currently available evidence, seem to clearly outweigh the risks observed to date.

A recent decision analytic modelling study found that the HIV prevention benefit of providing PrEP to pregnant and breastfeeding women in sub-Saharan Africa outweighed even a substantially increased risk of pre-term birth (as high as 30 percent).

For HIV-serodiscordant couples in which the infected partner starts ART, additional prevention options such as PrEP are still needed, because there is residual HIV transmission risk during the first six months of ART until viral suppression is achieved.

Although WHO calls for further research, current WHO guidelines are permissive for use of PrEP during pregnancy and breastfeeding, noting growing evidence for safety from maternal HIV and HBV studies. WHO is currently reviewing data on safety of PrEP in pregnancy and lactation and will provide more detailed guidance in the near future.

However, although it will be important to collect additional safety data, the weight of existing evidence does not support further delay in implementing TDF PrEP for pregnant and breastfeeding women at high risk of HIV acquisition. Those women on PrEP who become pregnant or are lactating should not have to stop an effective HIV prevention intervention.

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