groups » The Zambian Clinical Research Forum » Quantification of the amount of TDF/FTC/EFV (atripla) excreted in breast milk.
Looking at the new ART guidelines which advocate for ininitiation of full HAART to children born from reactive mothers who also start HAART regardless of CD4 count, would it prudent to ascertain how much drug is excreted in milk to avoid overdosing babies? If yes , briefly discuss the statement of the problem, what research design would be appropriate and what would be the research question?
Interesting clinical scenario here, it would be good to undertake such a clinical research.
I contend that a problem can be established from theoretical background & evidence documenting that TDF/FTC/EFV is excreted in breast milk. Also need to take account of whether or not babies born to HIV+ mothers (on or not on HAART) are usually breastfed or not and what the trend is in that particular setting.
Firstly, a drug screen analysis for concentration of active drug metabolites of TDF/FTC/EFV excreted in breast milk from lactating mothers on HAART can be done on to determine whether there are significant levels actually present in breast milk and whether or not the levels pose is significant risk to the baby, based on reference measurements. Having established that, I contend that secondly, a randomized clinical trial design to follow up one group of mothers on full HAART (TDF/FTC/EFV) but not breastfeeding their baby taking HAART (TDF/FTC/EFV) & another group of mothers on full HAART (TDF/FTC/EFV) breastfeeding their baby taking HAART (TDF/FTC/EFV). At baseline, during and at the end of the follow-up period the babies in the two groups will be assessed for overdose to TDF/FTC/EFV and compared accordingly.
The Potential research question I would pose: 'Does initiation of full HAART (TDF/FTC/EFV regimen) to children born from HIV+ mothers who also start HAART regimen regardless of CD4 count increase the risk of overdose to TDF/FTC/EFV in lactating babies?'
I would really like to hear your thoughts on this scenario you've given us Jimmy and deliberate further on it. What do you and the other group members think?
This is a very interesting scenario and it would be nice to know the thoughts of other members on how we can translate everyday work scenarios into research questions that can be able to contribute to evidence informed decision making.
That's an interesting question you have raised, first of all it would be a good idea to quantify how much of the drug is being excreted in the breast milk. Now looking at the issue of overdosing, i think it wouldn't be of very much importance here in Zambia as we do not allow reactive mothers to breast feed. I am with the idea that for them to come up with such guidelines i should suppose they already have conducted such a research which backs them up.
The amount of drug excreted in breast milk can be determined using HPLC analysis. This can be done by developing and validating sensitive method for detecting and quantifying drugs contained in the fixed dose combination product. Since the concentrations in the breast milk are likely to be minute (assumption), the sensitivity of the analytical method can be increased by using HPLC in tandem with mass spectroscopy (MS). There are already methods to detect and quantify tenofovir, emtricitabine and efavirenz as individual drugs. However, coming up with a method to simultaneously determine the three drugs would ensure faster analysis. So I think we start by following up mothers on these drugs and collect samples for analysis. As Titus has mentioned, mothers in the Zambian setting are not allowed to breastfeed, even manufacturers of this product strongly recommend that there should be no breastfeeding when this drug is being taken. However, should there be instances where that is happening, then we can design the study as suggested by Chichonyi.