[pronut-hiv] From NAM/Aidsmap:Early infant HIV diagnosis - Part 3

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

Post-test counselling
Counselling also has to be carefully adapted to address the concerns of parents whether the test result is positive and negative.

âWe have heard of reported parental neglect of some of the HIV-positive infants,â said Dr Karanja. He also reported that women whose babies turn out HIV-negative often believe that means that if they get pregnant again, their next babies will also be HIV-negative â which isnât always the case. âThere is a high desire for conception of HIV-negative babies. So we need to improve on our counselling skills so that they make informed decisions.â


What about breastfeeding?
But the biggest counselling issue concerns the dangers that women may stop breastfeeding their infant if they are told the result is negative, long before the woman has found replacement feeding options that are acceptable, feasible, affordable, sustainable and safe (AFASS). 

âOne of the real issues that we have by testing the infants at 6 weeks is that we risk early weaning. And we have data that clearly shows that HIV-negative babies who are weaned early die prematurely,â said Dr Homsy (see also http://www.aidsmap.com/en/news/1C6972FE-B40B-42BC-BC71-2BA36589535E.asp). 

âIf we test the baby and the baby is negative, we need to accompany that with very good counselling on infant feeding. We know from the recent guidelines by WHO that exclusive breastfeeding is protective and is important for nutrition where a mother does not fit the AFASS criteria. So especially in most of Africa, where most of our mothers cannot afford safer alternatives âwe should still talk about exclusive breastfeeding. There is not as much transmission if they can do exclusive breastfeeding rather than mixed feeding. So the test results should be accompanied by good counseling on nutrition,â said Dr Mudany. 

But Dr Nuwagaba-Biribonwoha of ICAP in Tanzania said that the problem of premature weaning may begin even before testing the infant. 

âWe had at least 100 children, who by the time we do the first DNA PCR, were not breastfeeding. So I think â not only at the time we receive the results, but also during PMTCT â that the messages about exclusive breastfeeding have to really be reinforced,â she said. 

Part of the problem is that there are a lot of mixed messages being put out about breastfeeding, with some projects going to great lengths to introduce formula feeding in some resource-limited settings.

In another presentation at the Implementersâ Meeting, Dr Saul Onyanga, from Kampala Uganda, said that programmes needed to send less ambiguous messages about infant feeding. âIf you look at a small programme at health facility level, one small project, it is very possible to intervene with formula feeding and support that community. But not at the national programme level.â 

âI agree with what people have said in terms of reinforcing the counselling strategy but this also reinforces the need to put mothers who are eligible on ART,â said Dr Homsy. âWe know that these mothers are the most likely to transmit because of the high viraemia. I donât think we have any arguments with breastfeeding at this point â the point is to make breastfeeding safe. And if we donât make that effort - putting the mother on treatment before they deliver, then we raise the chance of transmission.â 

Very reassuring data from two studies presented at the IAS meeting demonstrated that ART dramatically reduces the chances that breastfeeding women with HIV will transmit the virus to their infants (to below 1%, see http://www.aidsmap.com/en/news/4920CF7D-9E95-4C08-85A1-65F001CB6E60.asp) (Kilewo, Arendt). 


Effective transition to care
The real point of these testing protocols should be to get children into treatment and care.

âWe can do all the diagnostics that you want but if we do not put babies on treatment, why are we doing diagnostics?â said Dr. Gonzalez. âThis is for medical intervention â we have to put those babies on treatment because that's the main reason to doarly infant diagnostics.â

âAfter identification, we have to actively make certain these HIV-exposed infants get into care and treatment, so [early infant diagnosis] must be closely integrated with clinical training, mentoring and supervision,â said Dr Hailegiorgis. He noted that when his programme started: âThere was lack of coordination of lab and clinic activities at the beginning because those results which came back from the laboratories were not analysed in the beginning.â

Dr Gonzalez recommended training a focal person at each site who would be responsible for following early identification of HIV-exposed infants, tracking them through diagnosis, and making certain that their results are delivered and that the children are entered into care and treatment. 

But in many locales, as Dr. Karanja noted âthere is a lack of adequate facilities that offer care, support, and treatment for HIV-infected infants.â 

In Botswana, where the ART programme is particularly aggressive, about 35% of the infants who tested positive for HIV have been put on ART, and another 30% still in follow-up according to Dr Jimbo. But he reported disheartening outcomes for the rest, who either died before starting ART (7%), or their families refused to put them on ART (8%), or the infant was referred for ART but the outcome is listed as unknown (10%) or the infant simply could not be found.

Dr Angela Mushavi of Katatura State Hospital in Namibia said delays in getting HIV-positive children onto ART could lead to poor outcomes.

âMy experience with the HIV-DNA is the unfortunate incidents where we have a positive HIV DNA-PCR at 6 weeks, you go on to do clinical staging and CD4 criteria and the child is not yet eligible for ART. And then weeks later the child comes in and is dead! What are we doing for those children? Maybe we should be making a case for treating all HIV-positive infants instead of waiting until we actually have children dying on our hands,â she said.

MCH systems strengthening
Again, to get the most benefit out of early infant diagnosis, investment must be strengthened in the entire MCH platform that provides care to mothers and infants in resource-limited settings. 

Trying to implement or strengthen just one aspect of a programme, implementing DBS on its own, for instance, comes with risks, as was shown by a recent paper in JAIDS, which reported that when routine PMTCT service programmes were integrated into clinics in Zambia, delivery of other routine clinical services for pregnant women (as gauged by syphilis screening) suffered (http://www.aidsmap.com/en/news/9C6E664F-5029-4968-BFD7-A3BC3A083FB6.asp). Dr Hailegiorgis made a similar observation during the implementation of early infant diagnosis in Ethiopia. 

âWe had some challenges during this process with human resource issues because new tasks had to be given to PMTCT and primary care nurses and this has compromised their workflow, and there was also scaling up of specimen collecting which was at the expense of other activities,â he said. 

In order to avoid the danger of diverting existing resources towards DBS, we have to extend the capacity to deliver better maternal-child health on multiple fronts in tandem.

Looking forward
Some participants at last yearâs major conferences were looking towards a future where infant diagnosis will be easier and can be delivered on the spot. 

âI commend the efforts but a better test is needed that could be done at the site of the infant with a result right so we need to work on it,â Dr Renee Ridzon from the Gates Foundation said at the HIV Implementerâs meeting. 

Any progress that the Gates Foundation and/or commercial enterprises can make towards developing an inexpensive point-of-care HIV test that works in infants is more than welcome. But in her report on the state of the art in the field at the IAS conference one month later, Prof. Susan Fiscus wasnât too encouraging. 

âThereâs an awful lot of activity in this a the future and I do think this is where we are going but I donât think weâre there yet,â said Prof Fiscus. 

So in the meantime, specimens will still have to be transported to centralised labs to be tested. Perhaps further study will confirm the clinical utility of using standard viral load tests, which, if successful would streamline the process of laboratory scale-up. 

However, it is possible that a less expensive alternative to PCR testing could eventually be performed on the samples. Two are worth noting: the Cavidi Reverse Transcriptase (RT) Assay (ExaVir Load version 3), and the heat dissociated p24 antigen (hdP24A) assay. 

ExaVir Load uses standard ELISA laboratory equipment plus a reader from Cavidi to look for the HIV enzyme reverse transcriptase (and it should work with any subtype). Data presented at the IAS meeting suggest that the current version of the test is more sensitive and can now detect viral loads over 2000 copies/ml (Greengrass). 

Finally, there has been recent progress on using the hdP24A assay on DBS. This test would be much cheaper because âthe equipment is generally available, itâs less technologically complex; itâs less prone to contamination compared to PCR; it seems to be excellent for infant diagnosis; itâs very reproducible and it works quite well with DBS. But itâs still not as sensitive as the DNA assay if the mother of the infant is on ART, and we need more information on some of the subtypes,â said Prof. Fiscus. 

Another problem, pointed out by Dr Homsy at the Implementersâ meeting is that âthe test is not a commercially available assay, and furthermore, itâs difficult to roll out because every lab has to have its in-house standards made before you can use it,â he said. 

But perhaps a way could be found by some public-private partnership to package a standardised kit for hdP24A in much the same way that the Global Drug Facility is packaging âsmear microscopy kitsâ for TB (see http://www.aidsmap.com/en/news/E398B0C4-01D1-4946-B219-39741A8618A8.asp). The Foundation for Innovative Diagnostics at one time discussed doing something similar to package a safer version of MODS liquid culturing system for TB. 

But while work on newer and hopefully inexpensive technologies progresses, Dr Souleymane Sawadogo from CDC in Namibia who moderated the HIV Implementerâs Meeting succinctly summed up the need to scale-up existing laboratory capacity and roll-out DBS now. âThe thing is that babies are dying. They canât wait for usâ we have to push everything at the same time.â 

 

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