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managing a PMTCT infected 7 year old child with mutlidrug resistant HIV

By Tamirirashe Mahwire | 26 Oct, 2017

KIndly assist me with managing a 7 year old child who had PCR positive at birth and was started ABC/3tC / Alluvia until 2016. He was never virally suppressed on this regimen. We switched him to AZT/3TC /EFV which he currently is on . He continues to be unsuppressed latest Viral load is 672000. HIs genotype shows resistance to all NRTIs and NVP and EFV. He has high level resistance to most PIs except Darunavir which he has low level resistance . His mom is virally suppressed on TDF/FTC/EFV. Kindly review his attached resistance profile
regards

Replies

 

Nader Shalaka Replied at 8:26 PM, 26 Oct 2017

Dr. Mahwire
Very sad to hear that a child is having such a resistant HIV virus. It seems that it wasn't a `transmitted resistance` since the mother is virologically suppressed by WHO first-line.

It also seems that the child had (and probably still having) poor adherence to prescribed HAART which cause the `acquired` resistance.

Based on data you provided, 3 possible class combinations could be recommended [depends largely on availability!]:
1- An Integrase inhibitor (Dolutegravir or Raltegravir) + boosted Darunavir (twice daily)
2- An integrase inhibitor (Dolutegravir or Raltegravir) + Etravirine
3- Boosted Darunavir + Raltegravir + Etravirine [PMID: 19823069]

But I have questions:
- What is this child's CD4 count?
- Did or does he/she have any ADI?
- Would it be possible to stop HAART and wait until he is older (probably more adherent) [Yes SMART study says no to ART interruption!]?

Good luck

Rokaya Ginwalla Replied at 10:40 PM, 26 Oct 2017

Thank you for sharing your case with us. Thanks too to Nader for sharing insights and agree that the most likely reason for failure are adherence issues (may be related to vomiting or diarrhoea as well). We had a very similar case in Zambia: Orphaned early in life, treatment initiation at 1 year failed first line on AZT 3TC NVP then second line on ABC 3TC LPV/r.
Early this year aged 6y 8m and weight about 13 kg - found to be failing second line and further complicated by TB diagnosis at the time of failure. She also had high level resistance to all PI (low to DRV/r) and all the NRTI and NNRTI (low level to ETR) were resistant.
We ended up using DRV/r, RAL (doubled dose due to Rifampicin), and ETV in addition to TB treatment. Our patient had adherence issues as many different caregivers throughout her life with no consistent care and understanding of ART medications. Now 8 months later she is well suppressed, looked after by a consistent caregiver, and doing well. I wondered about the weight of your child and if she will be able to use DTG. We still don't have DTG in country and am not sure that it is FDA approved yet for children below 12years.
Also if you need to buy time and CD4 is high, then possibility of using 3TC only as holding therapy as you arrange for the best option.
Look forward to more suggestions and advice as third-line treatment for children is only just emerging and experience is fairly limited in our settings.

Ei Mon Khine Replied at 3:41 AM, 27 Oct 2017

Hi,

Thanks for sharing your case. May I summarize. The child is really failing to current ART regimen with resistance to all NRTIs, NVP and EFV, even low level resistance to ETR & high level resistance to almost all PI but DRV with low level resistance. The mother has got suppressed VL with TCF/3TC/EFV.

The child is 7 years old and HIV DNR (+)ve at birth : ~6 years on PI based regimen and ~ 1 year on NNRTI based regimen. The last VL was 672,000 copies/ml. When was it?

It would be great if latest CD4, current body weight and clinical condition are mentioned.

To choose the appropriate regimen for him : options are Integrase inhibitors, Darunavir and ETV (low level resistance). It will be salvage therapy.
-Dolutegravir : ok? (the child must be more than 30 kg and still awaiting approval to use in child in most countries)
- Etravirine : ok for above 6 years (should not be used together with Rifampicin)
-Darunavir : ok for him (It is the PI with the highest genetic barrier), need to be boosted with ritonavir
-Raltegravir : ok for him

I would choose RAL+DRV/r+ETR (+/- NRTI?) with further discussion and clinical assessment. With a caretaker(he has mother), it should be switched to effective regime asap. Since the latest VL was very high, I would not recommend stopping ART or continuing with 3TC monotherapy, which can make higher VL and lead to clinical failure.

references : https://aidsinfo.nih.gov/guidelines/html/2/pediatric-arv-guidelines

Regards,
Ei Mon

Elham Elhshik Replied at 3:42 AM, 27 Oct 2017

Thank you Tamirirashe for sharing the case. Thank you Nader and Rokaya for contribution.

I would like to add that FDA has approved DTG for children as young as 6 years with body weight 30 kg or more, which I doubt this poor kid have reach it. But the European Medicines Agency has approved DTG for children aged as young as 6 years weighing ≥15 kg.

Junior Bazile Moderator Replied at 7:26 AM, 31 Oct 2017

THank you all for your inputs and contributions to the care of the angel that Dr Mahwire is treating. I believe and hope that the combination of integrase inhibitors, protease inhibitors (Darunavir) and non-nucleoside reverse transcriptase inhibitors (etravirine) can be helpful in this serious case of resistance. I hope that the patient has already started a new regimen.
Dr Mahwire, please keep us updated on how your patient is doing.
All the best,

Bazile

Tamirirashe Mahwire Replied at 11:45 AM, 31 Oct 2017

Good afternoon. Thank you very much for your inputs. I work in the public
sector and we prescribe and dispense 3rd line medication i.e Darunavir,
intergrase inhibitors and second generation NNRTIS on recommendation from a
central Expert Committee. The committee feel that your patient does qualify
for 3rd line ART. However, for various reasons (e.g. age of patient, lack
of suitable formulations, patient unable to swallow large tablets,
adherence issues etc) the committee felt that it will not be practical to
start 3rd line ART at this point in time.

They have therefore recommended the temporary measure of the child being
placed on a holding regimen consisting of 3TC monotherapy. The aim of this
regimen is to prevent the CD4 from dropping too much while at the same time
preventing the evolution of more resistance. While on this holding regimen,
please repeat the CD4 every 3 months.

A third line regimen will be recommended when the CD4 drops to below 200
or the patient's condition deteriorates. At which point I will complete an
application form with the latest clinical information. I would like to
appeal to this forum if they knowledge on availability of paediatric
formulations and dosing for this age group for these 3rd Line medication. i
Have called the child back and on review will reasses clinical condition ,
immunological and virological status of child . I will continue to update
you on the child's medical condition.

SUILANJI SIVILE Replied at 1:44 PM, 2 Nov 2017

Thank you Tamirirashe for Sharing your case. The suggested regimens of INSTI+DRV-r+ ETV+(+/- NRTI) will work perfectly well in your patient. I would like to know the country where you are practising and exactly how the third line care is arranged.

Thank you.

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