Routine resistance and genotype testing is expensive and difficult to access. It should therefore only be done in consultation with an expert in HIV/AIDS and infectious diseases.  The value and use in both the public and private context is summarised below.

Private sector

Genotype testing may be of benefit to:

• Differentiate between adherence problems (no resistant mutations shown) and the presence of resistance
• Deciding which Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to use in 2nd-line therapy, although published results from the EARNEST trial (Europe-Africa Research Network for Evaluation of Second-line Therapy) showed that virological outcomes on a 2nd-line regimen containing  a protease inhibitor (PI) + NRTIs  (without determining resistance) were good and comparable to a PI + raltegravir (RAL) regimen
• Assist in subsequent use of NNRTIs such as etravirine (ETV) or rilpivirine (RPV) in 3rd-line regimens, based on mutations and full medication history

Testing following 1st-line failure may be considered, although 1st-line resistance profile is relatively predictable and genotyping is therefore often not essential, unless resources permit.

Eligibility for genotype testing is considered, provided funds permit and adherence has been confirmed (pre-approval may be required - refer to applicable medical scheme rules):

1. Confirmed virological failure on 1st or 2nd-line therapy:

• Viral load (VL) ≥ 1000 copies/ml on 2 or more occasions, preferably 2-3 months apart
• Second VL being measured after an intervention and evidence of improved adherence
• Genotype resistance test is performed while the patient is taking the failing regimen

2. Before initiating ART in children < 2 years, newly infected:

• Exposed to ART for PMTCT
• During breastfeeding when mother is on ART
• During breastfeeding and child receiving prophylactic nevirapine (NVP)

3. Before initiating ART in patients where there is a strong suspicion that they have been infected with a resistant virus (e.g. sexual partner failing ART)

Public sector

Standardised 1st and 2nd-line regimens are recommended. These are based on efficacy, safety and tolerability and take into account predictable resistance mutations that develop after 1st-line failure.

The 2nd-line regimens containing a PI, which are robust drugs (i.e. resistance develops slowly), should achieve viral suppression, as supported by findings in the EARNEST trial. No genotype test is required on initiation or after 1st-line failure in patients on an NNRTI regimen containing efavirenz (EFV) or nevirapine (NVP).

Genotype testing is generally only considered as follows (refer to relevant current national guidelines for further information):

1. Adults and late adolescents (>15 years; >40kg) with confirmed virological failure on a PI-containing 2nd-line regimen:

• At least 2 years exposure to a PI: resistance earlier than this is very uncommon unless there has been a medication error (e.g. giving standard dose LPV/r with rifampicin)
• Viral load (VL) ≥ 1000 copies/ml (≥log 3)on 2 or more occasions, preferably 2-3 months apart
• Second VL measured after an intervention and objective evidence of improved adherence
• Genotype resistance test is performed while the patient is taking the failing regimen

2. Infants, children and early adolescents (<15 years and < 40kg) failing on a PI-containing 1st or 2nd-line regimen
3. Newly diagnosed HIV-infected infant born to a mother failing 2nd or 3rd-line regimen
4. Individualised cases where a standardised regimen may not be appropriate (e.g. contraindication to NNRTIs and PIs, triple NRTI regimen)

Application for 3rd-line using the standard motivation form is required (available from TLART@health.gov.za). The regimen will be determined by an elected expert committee based on the pattern of resistant mutations and the prior history of antiretroviral exposure.

Other situations may exist where genotype testing can be considered.

If you require information regarding therapy failure, resistance and genotype testing, switching regimens, etc. please contact the National HIV & TB Health Care Worker Hotline (0800 212 506).

WRITTEN BY: Ewan Tommy

References:

• Paton NI, Kityo C, Hoppe A, et al. Assessment of second-line antiretroviral regimens for HIV therapy in Africa. N Engl J Med 2014;371(3):234-247
• Meintjes G, Black J, Conradie F, et al. Southern African HIV Clinicians Society adult antiretroviral therapy guidelines 2014. S Afr J HIV Med 2014;15(4):121-143.
• Republic of South Africa. Essential Drugs Programme. Primary Healthcare Standard Treatment Guidelines and Essential Medicines List. 5th ed. Republic of South Africa: National Department of Health; 2014.
• Republic of South Africa. Essential Drugs Programme. Hospital level (Adults) Standard Treatment Guidelines and Essential Medicines List. 4th ed. Republic of South Africa: National Department of Health; 2015.
• Republic of South Africa. National Consolidated Guidelines for the Prevention of Mother-to-Child Transmission of HIV (PMTCT) and the Management of HIV in Children, Adolescents and Adults. National Department of Health, South Africa. April 2015
• Regensberg L, Dunn L, Maharaj S (Eds). AidforAids Clinical Guidelines. 11th ed. Pinelands: Aid for AIDS Management; 2016