Treatment of HIV/AIDS in Children (ARV therapy)

hiv / aids Treatment in Children

TREATMENT MODALITIES IN PEDIATRIC HIV/AIDS 

  1. Antiretroviral therapy 
  2. Treatment of acute bacterial infections 
  3. Prophylaxis and treatment of opportunistic infections 
  4. Maintenance of good nutrition 
  5. Immunization 
  6. Management of AIDS – defining illnesses 
  7. Psychological support for the family 
  8. Palliative care for the terminally ill child

ANTIRETROVIRAL DRUG TREATMENT 

The goal of ART 

The aim of antiretroviral therapy is to suppress viral load levels amongst all PLHIV to undetectable levels,  and reduce the risk of morbidity and mortality associated with HIV, as well as reduce transmission of HIV.

When to initiate ART

  • All HIV infected children less than 12 months 
  • Clinical AIDS 
  • Mild to moderate clinical symptoms 
  • Mild to moderate immunosuppression 

When ART should be started 

ART should be initiated at the earliest opportunity in all people with confirmed HIV infection, regardless of  clinical stage or CD4 cell count.

The process of starting ART

Although the program recommends starting all PLHIV on ART, the health workers should do
the following:

  •  Assess all clients for opportunistic infections especially TB and cryptococcal meningitis. If the patient has TB or cryptococcal meningitis, ART should be deferred and initiated after starting treatment for these OIs. Treatment for other OIs and ART can be initiated concurrently.
  •  For patients without TB or cryptococcal meningitis, offer ART on the same day through an opt-out approach. In this approach, the patients should be prepared for ART on the same day and assessed for readiness to start ART using the readiness checklist 
  • If a client is ready, ART should be initiated on the same day. If a client is not ready or opts out of same-day initiation, a timely ART preparation plan should be agreed upon with the aim of initiating ART within seven days for children and pregnant women, and within one month for adults. 

Principles for selecting the ARV regimens 

The first-line ART regimens for treating HIV infection in Uganda were selected based on the following  principles: 

  • Regimen with lower toxicity 
  • Better palatability and lower pill burden 
  • Increased durability and efficacy 
  • Sequencing: spares other available formulations for use in the 2nd line regimen Harmonization of regimen across age and population 
  • Lower cost 
  • Help the country to achieve a recommended regimen for the vast majority of PLHIV(People Living With HIV)

Available ARVs in Uganda  

  1. Nucleoside reverse transcriptase inhibitors (NtRTIs): They incorporate themselves into the DNA of  the virus, thereby stopping the building process. 
  • Tenofovir (TDF) 
  • Zidovudine (AZT) 
  • Lamivudine (3TC) 
  • Abacavir (ABC) 
  1. Non-nucleoside reverse transcriptase inhibitors (NNRTIs): stop HIV production by binding directly  onto the reverse transcriptase enzyme, and prevent the conversion of RNA to DNA.
  • Efavirenz (EFV) 
  • Nevirapine (NVP) 
  • Etravirine (ETV) 
  1. Integrase inhibitors interfere with the HIV DNA’s ability to insert itself into the host DNA and copy  itself. 
  • Dolutegravir (DTG) 
  • Raltegravir (RAL) 
  1. Protease inhibitors (PIs): prevent HIV from being successfully assembled and released from the  infected CD4 cell. Boosted PIs are combinations of low-dose ritonavir (RTV) with a PI for pharmaco-enhancement. 
  • Atazanavir (ATV) 
  • Lopinavir (LPV) 
  • Darunavir (DRV) 
  • Ritonavir (RTV, abbreviated as ”r” if boosting other PIs, e.g. ATV/r, LPV/r 
  1. Entry inhibitors (HIV fusion inhibitors): prevent the HIV virus particle from infecting the CD4 cell. Enfuvirtide (T-20) 
  2. CCR5 antagonists: block the CCR5 co-receptor molecules that HIV uses to infect new target T-cells.  Some forms of HIV use a different co-receptor and thus, some patients may not benefit from  maraviroc. 
  • Maraviroc 

Uses of ART

  1. Treatment of HIV/AIDS. 
  2. Prevention of mother-to-child transmission 
  3. Post-exposure-prophylaxis (pep) 
  4. Pre-exposure prophylaxis (pep) 
  5. Treatment support in children is paramount so is adherence.

RECOMMENDED FIRST-LINE REGIMEN FOR INITIATING ART IN children AGED 10 AND ABOVE

The first-line ART regimen for adults and adolescents aged ten years and above consists of 2 nucleoside  reverse transcriptase inhibitors (NRTI) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI). 

All HIV-infected children aged 10 years and above should be initiated on tenofovir, lamivudine and  Efavirenz (TDF+3TC+EFV) as a once-daily fixed dose combination. 

WHEN TO USE ALTERNATIVE FIRST LINE REGIMENS 

When to use TDF+3TC+DTG 

Children aged 12 years and above should only be initiated on TDF+3TC+DTG if they have a condition where  EFV is contraindicated including: 

  • Severe clinical depression, psychosis or suicidal tendencies 
  • Ongoing complications of neurological disease that block the prescriber’s ability to assess side  effects of EFV 
  • Use of anxiolytics especially benzodiazepines or carbamazepine. 
  • Severe hepatic impairment 
  • HIV/TB co-infected PLHIV using Bedaquiline 
  • Situations where the only available FP method is hormonal contraception containing levonorgestrel,  ethinyl estradiol, or etonogestrel 

Rationale for using dolutegravir (DTG) 

Dolutegravir has a low potential for drug interactions, shorter mean time to viral suppression, higher  genetic resistance barrier, a long half-life and low cost. However information about its efficacy/safety  during pregnancy and in TB/HIV is still limited. 

When to use ABC+3TC+DTG 

Children of 10 years and above should only be initiated on ABC+3TC+DTG if TDF is contraindicated,  including the following conditions: 

  • Kidney disease and estimated glomerular filtration rate (GFR) below 60 ml/min
  • Adolescents below 35 kg of weight

RECOMMENDED FIRST-LINE REGIMEN FOR INITIATING ART IN CHILDREN 3 to <10 YEARS OF AGE

All HIV-infected children aged 3 to < 10 years of age should be initiated on abacavir + lamivudine + efavirenz  (ABC+3TC+EFV

NB: Using ABC in first-line regimens spares AZT for use in 2nd line. Also, ABC+3TC+EFV can now be given as  once a day dose which may improve adherence. 

When to use alternative first-line regimens ABC+3TC+NVP 

Children aged 3 to <10 years should only be initiated on ABC+3TC+NVP if EFV is contraindicated in the  following conditions: 

  • Diagnoses with severe clinical depression or psychosis 
  • Ongoing complications of neurological disease that block ability to assess side effects The use of benzodiazepines or carbamazepines

RECOMMENDED FIRST-LINE REGIMEN FOR INITIATION OF ART IN CHILDREN UNDER 3 YEARS OF AGE

Recommended first-line regimen: ABC+3TC+LPV/r 

All HIV-infected children under 3 years should be initiated on abacavir + lamivudine + ritonavir-boosted  lopinavir (ABC+3TC+LPV/r). 

NB: Children younger than 36 months have a reduced risk of discontinuing treatment, viral failure or death  if they start on an LPV/r based regimen instead of the NVP-based regimen. Also, surveillance of drug  resistance among vertically infected children younger than 18 months in 

Uganda has revealed high levels of resistance to NNRTIs and LPV/r is known to have a high barrier to  resistance. 

When to use alternative first-line regimens AZT+3TC+LPV/r 

AZT+3TC+ LPV/r should only be used in children who experience a hypersensitivity reaction to abacavir  (ABC), however, this is rare in African populations. 

WHAT REGIMEN TO SWITCH TO (SECOND-LINE AND THIRD-LINE ART) 

Second-line ARVS in adolescents/children above 10 years 

Recommended 2nd line regimen: 2 NRTIs +ATV/r 

HIV-infected adolescents/children above 10 years, initiating 2nd line ART should be initiated on 2 NRTIs and  ritonavir-boosted atazanavir (ATV/r). The choice of NRTI should be determined based on the regimen the  patient was on. 

The recommended sequence is: 

  1. After failing on TDF + 3TC or ABC+3TC based regimen, use AZT+3TC 
  2. After failing on AZT+3TC based regimen, use TDF + 3TC 

When to use alternative 2nd line regimen: 2 NRTIs +LPV/r 

LPV/r is should only be used to initiate adolescents/children who weigh less than 40kg. 

Second-line ARVS in children aged 3 years to less than 10 years 

RECOMMENDED 2nd line REGIMEN: 2 NRTIs +LPV/r 

HIV-infected children aged 3 to less than 10 years initiating 2nd line ART should be initiated on 2 NRTIs and  ritonavir-boosted lopinavir (LPV/r). The recommended formulation is the LPV/r 100/25mg tablet. The choice of NRTI should be determined based on the regimen the patient was on The recommended sequence of the NRTIs is below: 

After failing on ABC+3TC based regimen, use AZT+3TC. 

After failing on AZT+3TC based regimen, used ABC+3TC. 

Second-line ARVS in children under 3 years 

Recommended 2nd line regimen: 2 NRTIs +RAL 

HIV-infected children less than 3 years of age initiating 2nd line ART should be initiated on 2 NRTIs and RAL. The choice of NRTI should be determined based on the regimen the patient was on (Table 55). The recommended sequence of the NRTIs is: 

After failing on ABC+3TC based regimen, use AZT+3TC. 

After failing on AZT+3TC based regimen, used ABC+3TC. 

The rationale for using raltegravir

Raltegravir is the recommended drug of choice for the second line ARVs in children with prior exposure to  protease inhibitors because there is no data on safety and efficacy of dolutegravir in children under six  years, while darunavir is contraindicated in this age group. 

When to use alternative 2nd line regimen: 2 NRTIs + LPV/r 

LPV/r is recommended in children who have used NNRTI (NVP) in their first line regimen.

Summary of ARV treatment in HIV/pediatrics

No. 

Population 

Patients failing 1st line  

regimen

Second line regimens 

Third line regimen

 

Children above 10  years/adolescents 

TDF + 3TC + EFV 

AZT+3TC+ATV/r 

(recommended) 

or 

AZT+3TC+LPV/r 

(alternative)

All 3rd line regimens to be guided by resistance testing If patient is not exposed to INSTIs, DRV/r +DTG ± 1-2 NRTIs

TDF + 3TC + DTG

ABC + 3TC + EFV

ABC + 3TC + NVP

TDF + 3TC + NVP

 

  

AZT + 3TC + NVP 

TDF+3TC+ATV/r 

(recommended) 

or 

TDF+3TC+LPV/r

If patient is exposed to 

INSTIs, DRV/r + ETV±1-2 

NRTIs 

AZT + 3TC + EFV

 

Children 3–<10 

years

ABC + 3TC + EFV 

AZT + 3TC + LPV/r 

For children above 6 years, and prior exposure to 

ABC+ 3TC + NVP INSTIs,  

DRV/r±1-2 NRTIs

ABC + 3TC + NVP

AZT + 3TC + NVP 

ABC + 3TC + LPV/r 

For children below 6 years,  DRV/r + RAL+ 2 NRTIs

AZT + 3TC + EFV 

AZT + 3TC + LPV/r 

ABC + 3TC + RAL 

Optimize regimen using 

genotype profile plus DRV/r +  2 NRTIs

ABC + 3TC + LPV/r 

AZT + 3TC + RAL

 

Children under 3  years

ABC+3TC+LPV/r pellets 

AZT+3TC+RAL 

Optimize regimen using  

genotype profile

AZT+3TC+LPV/r pellets 

ABC+3TC+RAL 

AZT+3TC+NVP 

ABC+3TC+LPV/r

1-All PLHIV should receive resistance testing to inform the prescription of 3rd-line medicines

2-Since all 3rd-line PLHIV will have prior PI Exposure, DRV/r will be 600/100mg taken twice a day.

MONITORING OF ARV TREATMENT 

The purpose of monitoring patients on ART is to assess: 

  • Response to ART and diagnose treatment failure 
  • Safety of the medicines- side effects and toxicity 
  • Adherence to ART 
Methods of monitoring ARV treatment 
  • Clinical monitoring 

Clinical monitoring involves taking a medical history and doing a physical exam. In this section, we shall  describe a comprehensive clinical assessment for patients who are well and are in the fast track model of  differentiated service delivery. 

  • Laboratory monitoring 

Involves taking laboratory tests 

The following are laboratory tests done 

  1. Viral load monitoring 
  2. CD4 monitoring 
  3. Other minor laboratory tests 

Viral load monitoring 

Uganda adopted viral load monitoring as the preferred approach for monitoring response to ART and to  diagnose/confirm ART treatment failure. Compared to clinical or immunological monitoring, virological  monitoring: 

  1. Provides an early and more accurate indication of treatment failure and the need to switch from  first-line to second-line drugs, hence reducing the accumulation of drug resistance mutations and  improving clinical outcomes. 
  2. Can also help to distinguish between treatment failure and non-adherence.
  3. A patient who has been on ART for more than 6 months and is responding to ART should have viral  suppression (VL <1000 copies/ml) irrespective of the sample type (either DBS or plasma). 

Facilities should constitute a multidisciplinary VL review committees to review, track, and make decisions  about switching to 2nd line. At the minimum, the committee should consist of a health care worker and a  lay provider (e.g. expert client, counselor, peer education, VHT) who know the client. Frequency of viral load 

Children and adolescents under 19 years of age: the first VL test should be done at six months after  initiating ART, and if it is suppressed, do VL every six months. 

CD4 monitoring 

Although CD4 cell count is no longer the mainstay for ART response monitoring and is not a pre-condition  for initiating ART, it is still recommended in the following scenarios: 

  1. At baseline when initiating ART. Baseline CD4 helps to screen for risk for opportunistic infections,  e.g. cryptococcal infection in patients with CD4 less than 100 cells/mm3 
  2. ART patients with VL >1000 copies/ml and/or WHO clinical Stage 3 or 4 disease PLHIV who are on treatment or prophylaxis for cryptococcal infection to inform decision on when to  stop fluconazole 

Other laboratory tests 

No. 

Tests 

indication

1. 

CrAg 

(CD4 <100 cells/mm3)

2. 

Complete blood 

count (CBC)

Patients at risk of anaemic conditions, e.g. patients on AZT,  anti-cancer 

drugs, chronic renal disease, etc.

3. 

TB tests 

If TB is suspected

4. 

Serum creatinine 

If PLHIV has comorbidities (DM, hypertension)

5. 

ALT, AST 

Compromised liver function, e.g. hepatitis B or C infection,  ART hepatotoxicity

6. 

Lipid profile and 

blood glucose

If PLHIV has comorbidities (diabetes mellitus, hypertension)  or lifestyle risk factors or on ART for more than five years 

Problems associated with ARV treatment 

  • Immune reconstitution inflammatory syndrome (IRIS) 

IRIS is a spectrum of clinical signs and symptoms thought to be associated with immune recovery brought  about by a response to ART. It is a widely recognized phenomenon that occurs among 10–30% of the  people initiating ART, usually within the first 4–8 weeks after initiating therapy. IRIS should be considered  only when the presentation cannot be explained by a new infection, the expected course of a known  infection, or drug toxicity. The most serious and life-threatening forms of IRIS occur in patients co-infected  with TB, Cryptococcus, Kaposi’s sarcoma and herpes zoster. BCG vaccine–associated IRIS (localized and  systemic) may occur in infants infected with HIV in settings where BCG immunization is routine. 

Risk factors for IRIS 

  • Low CD4+ cell count (<50 cells/mm3) at ART initiation 
  • Disseminated opportunistic infections or tumors and/or a shorter duration of therapy for  opportunistic infections before ART starts. 

Managing IRIS 

IRIS is generally self-limiting, and interruption of ART is rarely indicated. Treat any coinfections to reduce  morbidity and symptoms. If the symptoms are protracted, reassure the patient to prevent discontinuation  of, or poor adherence to ART. 

Steps to reduce development of IRIS 

  • Diagnose HIV early and initiate ART before CD4 declines to below 200 cells/mm3. Screen and optimally  manage opportunistic infections before initiating ART, especially TB and cryptococcus. The timing of ART in people with opportunistic infections requires balancing a greater risk of IRIS after early initiation against  continuing high mortality if ART is delayed. 

ARV DRUG TOXICITY 

  1. Antiretroviral drugs can cause a wide range of toxicities, from low-grade intolerance that may be  self-limiting to life-threatening side effects.  
  2. Differentiating between ART toxicity (also known as adverse reactions) and complications of HIV  disease is sometimes difficult.  
  3. An observed toxicity could be due to a concurrent infectious process or due to a reaction to  medications other than ARVs such as isoniazid–induced hepatitis in a child on treatment for TB or a  rash induced by cotrimoxazole. 
  4. Drug-related side effects while on ART can occur immediately (soon after a drug has been  administered), early (within the first days or weeks of treatment) or late (after months or years of  treatment). Adverse reactions may be specific to a particular drug, or they may be generic to the  class of drugs in use. Toxicity is a concern because it can be life-threatening, can cause non adherence to ARVs, and may be disfiguring like lipodystrophy. 

Managing ARV drug toxicity 

Health care workers should assess patients on ART for ARV side effects and toxicities at every clinic visit. If  the patient has side effects or toxicity do the following: 

  1. Determine the seriousness of the toxicity. 
  2. Evaluate concurrent medications and establish whether the toxicity may be attributable to an ARV  drug or drugs, or to a non-ARV medication taken at the same time. 
  3. Consider other disease processes. Not all problems that arise during treatment are caused by ARV  drugs. 
  4. Manage the side effects and toxicities according to severity (Table 51). 
  5. Report the event using the National Drug Authority (NDA) adverse drug reaction form. 
Management of ARV side effects/toxicities 

No. 

Category 

Action

1. 

Severe, life-threatening  reactions

Immediately discontinue all ARV drugs, manage the medical  event and substitute the offending drug when the patient is  stable.

2. 

Severe reactions 

Substitute the offending drug without stopping the ART.

3. 

Moderate 

Reactions

Substitute with a drug in the same ARV class but with a different  toxicity profile, or with a drug in a different class. 

Do not discontinue ART. Continue ART as long as feasible. If the  patient does not improve on symptomatic therapy, consider  single –drug substitution.

4. 

Mild reactions 

Do not discontinue or substitute ART. 

Reassure the patient or caregiver that while the reaction may be  bothersome, it does not require a change in therapy; provide  support to mitigate the adverse reactions as well as counseling  about the events.

Care of HIV Exposed Infant 

HIV-exposed infants should receive care at the mother-baby care point together with their mothers until  they are 18 months of age. The goals of HIV-exposed infant care services are: 

  • To prevent the infant from being HIV infected 
  • Among those who get infected: to diagnose HIV infection early and treat 
  • Offer child survival interventions to prevent early death from preventable childhood illnesses 

The HIV Exposed Infant and the mother should consistently visit the health facility at least nine times during  that period. 

The visits are synchronised with the child’s immunization schedule (i.e., at 6, 10 and 14 weeks, then at 5, 6,  9, 12, 15 and 18 months). 

Nevirapine prophylaxis 

Provide NVP syrup from birth for 6 weeks 

Give NVP for 12 weeks for babies at high risk, that is breastfeeding infants who mothers: 

  •  Have received ART for 4 weeks or less before delivery; or 
  •  Have VL >1000 copies in 4 weeks before delivery; or 
  •  Diagnosed with HIV during 3rd trimester or breastfeeding period (Postnatal) 

Do PCR at 6 weeks (or at first encounter after this age) and start cotrimoxazole prophylaxis 

  •  If PCR positive, start treatment with ARVs and cotrimoxazole and repeat PCR (for  confirmation) 
  •  If PCR negative and baby never breastfed, child is confirmed HIV negative. Stop  cotrimoxazole, continue clinical monitoring and do HIV serology test at 18 months.
  •  If PCR negative but baby has breastfed/is breast feeding, start/continue cotrimoxazole  prophylaxis and repeat PCR 6 weeks after stopping breastfeeding 

Follow up any exposed child and do PCR if they develop any clinical symptom suggestive of HIV at  any time and independently of previously negative results 

For negative infants, do serology at 18 months before final discharge. 

Dosages of Nevirapine 

Child 0-6 weeks, 2-2.5 Kg: 10 mg once daily (1 ml of syrup 10 mg/ml) 

Child 0-6 weeks, > 2.5 kg: 15 mg once daily (1.5 ml of syrup 10 mg/ml) 

Child 6 weeks – 12 weeks: 20 mg once daily (2 ml) 

Cotrimoxazole prophylaxis 

Provide cotrimoxazole prophylaxis to all HIV exposed infants from 6 weeks of age until they are  proven to be uninfected. Dosages: 

▪ Child <5 kg: 120 mg once daily 

▪ Child 5-14.9 kg: 240 mg once daily 

Infants who become HIV infected should continue to receive cotrimoxazole prophylaxis for life If cotrimoxazole is contraindicated, offer dapsone at a dose of 2 mg/kg once daily ( up to 100 mg  max) 

Isoniazid (INH) preventive therapy (IPT) 
  • Give INH for six months to HIV-exposed infant who are exposed to TB (close contact with PTB case)  after excluding TB disease. 
  • Dose: Isoniazid 10 mg/kg + pyridoxine 25 mg daily 
  • For newborn infants, if the mother has TB disease and has been on anti-TB drugs for at least two  weeks before delivery, INH prophylaxis is not required. 

Immunization 

  • Immunize HIV exposed children as per national immunization schedule 
  • In case of missed BCG at birth, do not give if child has symptomatic HIV 
  • Avoid yellow fever vaccine in symptomatic HIV  
  • Measles vaccine can be given even in symptomatic HIV 

Counselling on infant feeding choice 

  • Explain the risks of HIV transmission by breastfeeding (15%) and other risks of not breastfeeding  (malnutrition, diarrhoea) 
  • Mixed feeding may also increase risk of HIV transmission and diarrhoea 
  • Tell her about options for feeding, advantages, and risks 
  • Help her to assess choices, decide on the best option, and then support her choice

Feeding options 

  1. Recommended option: Exclusive breastfeeding then complementary feeding after child is 6 months  old 
  2. Exclusive breastfeeding stopping at 3-6 months old if replacement feeding possible after this If replacement feeding introduced early, mother must stop breastfeeding 
  3. Replacement feeding with home-prepared formula or commercial formula and then family foods  (provided this is acceptable, feasible, safe, and sustainable/ affordable) 

If mother chooses breastfeeding 

  • The risk may be reduced by keeping the breasts healthy (mastitis and cracked nipples raise HIV  infection risk) 
  • Advise exclusive breastfeeding for 3-6 months

If mother chooses replacement feeding 

  • Counsel and teach her on safe preparation, hygiene, amounts, times to feed the baby etc.
  • Follow up within a week from birth and at any visit to health facility.

 

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