Antiretroviral Therapy, Adults and Adolescents (10-19 years old)

Individuals ≥30kg and ≥10 years
TDF + 3TC + DTG (“TLD”)
LoE:IIa⁹

Note:
DTG-based regimens are now recommended as first line ART in all women of childbearing potential

 LoE:IIa¹⁰

Patients on rifampicin-based TB treatment:
TDF + FTC + EFV

OR

TDF + 3TC + DTG plus additional dose of DTG 50 mg 12 hours later.
The extra DTG dose can be stopped two weeks after stopping rifampicin.
LoE:IIIb¹¹

(Also see: HIV in pregnancy)

Start protease inhibitor-based regimen:
TDF + 3TC/FTC + ATV/r
 LoE:IIb¹²

Note: If patient requires rifampicin-based TB treatment, substitute ATV/r with LPV/r at 800/200 mg 12-hourly.

Note: There is an increased risk of ALT/AST elevations and gastrointestinal disorders. LPV/r dose should be gradually titrated upward over 1-2 weeks (e.g. 600/150 mg and then 800/200 mg).

The LPV/r can be switched back to ATV/r two weeks after completion of TB therapy.

If chronic hepatitis B coinfection and eGFR 30-50 ml/min:
TAF + FTC + DTG.
LoE:IIb¹³

Other scenarios:
ABC + 3TC + DTG
LoE:IIb¹⁴

If plasma VL >50 copies/mL:
- Address adherence, tolerability, medicine interactions & psychosocial factors.
- Repeat VL test 3 months later.

If plasma VL remains > 50:
- Assess adherence, tolerability, medicine interactions & psychosocial factors again.
- If on TLD <2 years, or persistent low-level viraemia (50-999 copies/mL), or adherence suboptimal, repeat VL at next scheduled visit (i.e. in 6 months’ time).
- If on TLD >2 years and ≥2 consecutive VL ≥1000 copies/mL (or 1 VL ≥1000 copies/mL plus CD4 <200 or opportunistic infection), discuss with an HIV expert* whether a resistance test is indicated (as a rule it is not, and efforts to resolve adherence issues should be intensified instead).

Patient on:

- TDF/FTC/EFV

- ABC/3TC/EFV (or NVP)

- AZT/3TC/EFV (or NVP)

- AZT/3TC/DTG

- Any LPV/r- or ATV/r-containing regimen for <2 years

- Any LPV/r- or ATV/r-containing regimen with latest VL <1000 copies/mL

Switch to DTG-containing regimen regardless of VL result:

TDF + 3TC + DTG (“TLD”)
(Refer to Figure 1: Switching existing clients to DTG-containing regimens below).

If contraindications to DTG or TDF, use alternative regimen as in “Initiating ART” section above.

LoE:IIb¹⁶

If adherence >80%, discuss with an HIV expert to authorise and interpret a resistance test before switching.* Provide individualised regimen as recommended by HIV expert. If adherence < 80%. switch to DTG-containing regimen:

TDF + 3TC + DTG (“TLD”) If contraindications to DTG or TDF, use alternative regimen as per “Initiating ART” section above.

LoE:IIb¹⁷

Any DTG resistance shown on genotype authorised by HIV expert

Discuss case with an HIV expert*.

The regimen will be determined by an Expert Committee based on the pattern of resistant mutations and the prior history of antiretroviral exposure.

Application for 3rd line using the standard motivation form may be required (available from TLART@health.gov.za or from https://www.righttocare.org/)

Rifampicin-based TB treatment

If on DTG:
Add DTG 50 mg 12 hours after TLD dose.

LoE:IIIb¹⁸

If on ATV/r:
Switch ATV/r to LPV/r 800/200 mg 12 hourly (i.e. double dose).

Note: There is an increased risk of ALT/AST elevations and gastrointestinal disorders. LPV/r dose should be gradually titrated upward over 1-2 weeks.

The LPV/r can be switched back to ATV/r two weeks after completion of TB therapy

• WHO staging See HIV Infection in Adults and Adolescents (10-19 years old).
• Check CD4 count.
• If CD4 <200 cells/mm³:
  • Check cryptococcal antigen (If positive, perform LP regardless of whether symptoms are present or not). CrAg testing is done reflexly on the CD4 sample if CD4 <100 cells/mm³. If patient's CD4 is 100-199, a serum CrAg test must be ordered separately.
  • Initiate cotrimoxazole prophylaxis (See Cotrimoxazole prophylaxis).

LoE:IVb¹⁹

• Screen for pregnancy or ask if planning to conceive.
• Screen for mental health, STIs and NCDs.
• Screen for TB using the WHO screening questionnaire (any one of cough, fever, night sweats, or weight loss).
• Sputum TB-NAAT* in all who can produce sputum, regardless of symptoms.
• Urine LAM for inpatients, or outpatients who are symptomatic if CD4 <200 or advanced HIV disease or current serious illness.
• If planning to use TDF: check creatinine (avoid TDF if eGFR <50 mL/minute).
• Haemoglobin
• Check HBsAg (if positive, TDF should form part of the regimen).
• Cervical cancer screening

LoE:IIIb²⁰, LoE:IIb²¹

*TB-NAAT: TB Nucleic Acid Amplification Test (e.g. GeneXpert Ultra MTB/RIF)

• Monitoring schedule has been adapted to minimise the number of visits required per annum.
• VL at 3 and 10 months after initiating ART and every 12 months thereafter, if virologically suppressed. Align timing with client's scripting cycle.
• CD4 at 10 months after initiating ART (align with VL). Stop CD4 count monitoring when >200 cells/mm³ and virologically suppressed. If virological or clinical failure occurs, or if client returns >90 days after missing an appointment, then a CD4 count should be done as cotrimoxazole may need to be commenced/re-commenced. Repeat CD4 count every 6 months if VL remains ≥ 1000 copies/mL.
• If on TDF: creatinine at month 3, month 10, and every 12 months thereafter. Align with VL monitoring schedule.
• If on AZT: FBC and differential count at 1 and 3 months after initiating AZT, then only if clinically indicated.
• ALT if symptoms of hepatitis develop.
• If on a protease inhibitor (PI): cholesterol and triglycerides at 3 months after initiating PI. If above acceptable range, do fasting cholesterol and TGs and if still above acceptable range, obtain expert advice.

- Hypersensitivity (rare, weeks)
- Insomnia (common)
- Headache (common)
- Other neuropsychiatric symptoms
- Nausea, diarrhoea (common)
- Hepatitis (uncommon)
- Increase in serum creatinine (<30 mmol/L within the first few weeks of DTG initiation) due to inhibition of creatinine secretion by DTG; this is clinically insignificant as glomerular filtration rate is not reduced but will modestly affect eGFR which is determined using serum creatinine.

Dose adjustment not required

eGFR 15-29 mL/min:
200 mg every 3 days

eGFR <15 mL/min:
200 mg every 4 days

Note: FTC is not available as a singleingredient formulation

25 mg daily

If co-formulated with FTC, avoid if eGFR <30 ml/min.

If used as a single agent, avoid if eGFR <15 ml/min and not on haemodialysis.

- Acute kidney injury (rare - weeks to months).
- Decline in eGFR (months to years).
- Fanconi syndrome (rare – months to years).
- Reduced bone mineral density (months to years).

- Central nervous system symptoms: vivid dreams, problems with concentration, confusion, mood disturbance, psychosis (days to weeks).
- Encephalopathy, often with cerebellar features (uncommon – months to years).
- Rash (1 to 6 weeks).

LoE:IVb²³

- Hepatitis (weeks to months)
- Gynaecomastia.

Increased dose frequency to 50 mg 12 hourly.

Note: Continue increased dose for 2 weeks after rifampicin is stopped, then decrease to usual dose.

Double the dose of LPV/r to 800/200 mg 12-hourly.
Note: There is an increased risk of ALT/AST elevations and gastrointestinal disorders. Increase dose gradually over 1-2 weeks.

Adjusted dose should be continued for 2 weeks after rifampicin is stopped.

Avoid co-administration if possible.
Consider valproate or lamotrigine.

For carbamazepine:
Double DTG dose to 50 mg 12 hourly.

Metformin initiation:
Initiate metformin at a low dose (500-1000mg total daily dose), titrating up as needed. Do not exceed 2 g daily.

DTG initiation:
If patient stabilised on metformin dose ≤ 2g daily, retain metformin dose and monitor for side effects. If patient stabilised on >2g daily, reduce dose of metformin to ≤ 2g daily and monitor.

Patients with renal impairment:
Close monitoring of renal function required. Do not co-prescribe if eGFR <30mL/min.

Avoid co-administration.
Consider valproate or lamotrigine.

Avoid co-administration.

LoE:IIIb²⁷

Double LPV/r dose.

Note: There is an increased risk of ALT/AST elevations and gastrointestinal disorders. LPV/r dose should be gradually titrated upward over 1-2 weeks (e.g. 600/150 mg and then 800/200 mg).

Adjusted dose of LPV/r should be continued for 2 weeks after rifampicin is stopped.

The LPV/r can be switched back to ATV/r two weeks after completion of TB therapy.

If ATV/r or DVR/r is required, rifampicin must be replaced with dose-adjusted rifabutin (doctor prescribed) - See Antiretroviral therapy.