Neobook — clinical reference

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Click here to access the Adult Hospital Level Chapter 10: HIV_and_AIDS_with_supporting_NEMLC_Report_Reviews_2025-9-Version-1.0-26-February-2026

Eligibility for ART

Psychosocial indicators of readiness for ART

ART regimens

ART: dosing and important adverse effects

ART drug-drug interactions

Monitoring on ART

HIV viral load monitoring schedule

Comprehensive guidelines are available for ART and the care of adults and children with HIV infection in the 2023 ART Clinical Guidelines for the Management of HIV in Adults, Pregnancy and Breastfeeding, Adolescents, Children, Infants and Neonates.ⁱ

B24

Antiretroviral therapy (ART) consists of combinations of antiretroviral medicines that are capable of suppressing HIV replication (defined as an undetectable viral load). Continued use of ART with a detectable viral load results in the development of resistance to some or all of the medicines in the regimen. High levels of adherence are essential for long-term success with ART.

The current recommended first-line ART regimen contains two nucleoside reverse transcriptase inhibitors (NRTIs) together with an integrase strand transfer inhibitor (InSTI) dolutegravir. Previously a non-nucleoside reverse transcriptase inhibitor (NNRTI), efavirenz or nevirapine, together with two NRTIs, were recommended for first-line ART. Dolutegravir is better tolerated than the NNRTIs and has a much higher barrier to the development of resistance.

Dolutegravir, together with two NRTIs, is now also recommended in a patient who has failed an NNRTI-based (formerly first-line) regimen. Previously a protease inhibitor (PI), together with two NRTIs, was recommended for secondline ART, but dolutegravir is better tolerated than PIs. Switching people established on ART to the newer dolutegravir-based ART regimens needs to be carefully done to reduce the risk of the emergence of resistance (refer to National Department of Health HIV Guidelines and “Switching existing clients to DTG-containing regimens” see Table 1: ART regimens

ELIGIBILITY FOR ART

Eligibility to start ART:
All adults with confirmed HIV infection, irrespective of CD4 count or WHO clinical stage.

LoE:Iaⁱⁱ

Immediate Initiation:
ART should be initiated immediately in pregnancy and during breastfeeding.

LoE:IIaⁱⁱⁱ

Timing of ART initiation:

Where a patient is willing and ready, ART should be initiated on the same day as HIV diagnosis, except in patients with TB or cryptococcal meningitis (see Timing of ART initiation below).
In TB co-infection, start with TB treatment first, followed by ART initiation according to CD4 count (except TB meningitis – see below):
- CD4 <50 cells/mm³: initiate ART within 2 weeks of starting TB treatment.
- CD4 ≥50 cells/mm³: defer ART until 8 weeks after starting TB treatment, which does not increase the risk of mortality and reduces the risk of deterioration due to IRIS.

LoE:Ia^iv

In patients with TB meningitis (irrespective of CD4 count), defer ART until 8 weeks after initiating TB treatment.

LoE:IIIa^v

In patients with cryptococcal meningitis, defer ART until 4–6 weeks after starting antifungal treatment (earlier initiation has been shown to increase the risk of death).

LoE:IIIa^vi

In patients with positive cryptococcal antigen and no evidence for meningitis on LP, there is no need to delay. ART can be started immediately.

LoE:IVb^vii

PSYCHOSOCIAL INDICATORS OF READINESS FOR ART

It is essential that patients have good insight into the need for long-term therapy and high levels of adherence. Pay careful attention to adherence planning. Encourage patients to disclose their HIV status to somebody to act as a treatment supporter. If this is not possible then the patient should join a support group.
Manage depression.
Active substance abuse/alcoholism is an impediment to adherence and, if possible, should be addressed prior to initiating ART.

LoE:IIIb^viii

ART REGIMENS

INITIATING ART
Treatment-naïve patients	Individuals ≥30kg: TDF + 3TC + DTG (“TLD”) LoE:IIa^ix Note: DTG-based regimens are now recommended as first line ART in all women of childbearing potential. LoE:IIa^x Patients on rifampicin-based TB treatment: TDF + FTC + EFV OR TDF + 3TC + DTG plus additional dose of DTG 50 mg 12 hours later. LoE:IIIb^xi (Also see: HIV in pregnancy)
Contraindications/ intolerance to DTG	TDF + 3TC/FTC + EFV
Contraindications to EFV and DTG	Start a protease inhibitor-based regimen: TDF + 3TC/FTC + ATV/r LoE:IIb^xii Note: if patient requires rifampicin-based TB treatment, substitute ATV/r for LPV/r to 800/200 mg 12-hourly. 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 two weeks after completion of TB therapy.
Contraindication to TDF - eGFR <50 mL/minute.	If chronic hepatitis B coinfection and eGFR 30-50 ml/min: TAF + FTC + DTG. Other scenarios: ABC + 3TC + DTG LoE:IIIb^xiii
Contraindication to TDF/TAF and ABC intolerance/hypersensitivity	AZT + 3TC with DTG
Note: In the unlikely scenario where there is intolerance/contraindication to all currently available NRTIs, the following alternative dual-therapy regimens may be used after consulting a specialist: - DTG + 3TC (if no resistance/intolerance to 3TC and VL <500 000 copies/mL) - EFV + LPV/r - DTG + LPV/r LoE:IIb^xiv

VIROLOGICAL FAILURE
Management of viraemia on TLD	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 lowlevel 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).
SWITCHING EXISTING CLIENTS TO DTG-CONTAINING REGIMENS
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”) If contraindications to DTG or TDF, use alternative regimen as for first line above. LoE:IIb^xv
Patient on: - ATV/r or LPV/r regimen for >2 years and ≥2 consecutive viral loads ≥1000 copies/mL	If adherence >80%, discuss with an HIV expert* to authorise and interpret a resistance test before switching. If adherence < 80%, switch to DTGcontaining regimen: TDF + 3TC + DTG (“TLD”) If contraindications to DTG or TDF, use alternative regimen as for first line above. LoE:IIb^xvi
CLIENTS WITH DTG RESISTANCE
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 3^rd line using the standard motivation formmay be required (available from TLART@health.gov.za or from https://www.righttocare.org/)
RIFAMPICIN-BASED TB TREATMENT
Rifampicin-based TB treatment	If on DTG: Add DTG 50 mg 12 hours after TLD dose. LoE:IIIb^xvii 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.

ABC=Abacavir, ATV/r=Atazanavir/ritonavir, AZT=Zidovudine, 3TC=Lamivudine, DTG= Dolutegravir, EFV=Efavirenz FTC=Emtricitabine, LPV/r=Lopinavir/ritonavir, TDF=Tenofovir disoproxil fumarate TAF= Tenofovir alafenamide

Table 1: ART regimens
*For advice from an HIV expert, approach an HIV Hotline, an infectious disease specialist, or the Third Line ART committee.
HIV Hotlines:

National HIV & TB Health Care Worker Hotline: 0800 212 506
Right to Care Paediatric, Adolescent and Adult HIV Helpline: 082 352 6642
KZN Paediatric Hotline: 0800 006 603

Note:

Always check hepatitis B surface antigen (HBsAg) before stopping TDF

If patient has chronic hepatitis B, stopping TDF may lead to a fatal hepatitis flare.

Continue TDF if HBsAg positive.

Currently available ARV FDC preparations on contract:
• ABC 600 mg + 3TC 300 mg
• TDF 300 mg + FTC 200 mg
• AZT 300 mg + 3TC 150 mg
• LPV 100 mg + ritonavir 25 mg
• LPV 200 mg + ritonavir 50 mg
• TDF 300 mg + FTC 200 mg + EFV 600 mg
• TDF 300mg + DTG 50 mg + 3TC 300 mg
• ATV 300mg + ritonavir 100mg
• ABC 600mg + 3TC 300mg + DTG 50mg
Source: Contract circular HP13-2022ARV http://www.health.gov.za/

RE-INITIATING ART IN PATIENTS WHO HAVE INTERRUPTED TREATMENT:

Do VL, recommence ART regimen unless there is a clinical indication to defer ART, repeat VL at 3 months. Recommence previous regimen (unless patient would qualify for a switch to TLD anyway as per above, in which case start dolutegravir-based regimen, e.g. TLD).
If VL does not to decrease to <1000 copies/mL at 3 months, manage as per virological failure above.

LoE:IIIb^xviii

ART: DOSING AND IMPORTANT ADVERSE EFFECTS

Class: NRTI

Generic name and Class	Usual dose	Renal adjusted dose	Important adverse drug reactions (ADRs) and timing
Tenofovir disoproxil fumarate (TDF)	300 mg daily	Avoid in renal impairment (eGFR <50 mL/min)	- 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).
Abacavir (ABC)	600 mg daily	Dose adjustment not required	- Hypersensitivity reaction (1 to 6 weeks) fever, rash, constitutional symptoms, gastrointestinal symptoms and respiratory symptoms.
Zidovudine (AZT)	300 mg 12 hourly	eGFR <10 mL/min: 300 mg daily	- Anaemia, neutropenia (weeks to months). - Gastro-intestinal upset. - Headache. - Myopathy (rare). - Hyperlactataemia / steatohepatitis (medium risk - months). - Lipoatrophy (months to years).
Lamivudine (3TC)	300 mg daily (or 150 mg 12 hourly)	eGFR 10-30 mL/min: 150 mg daily eGFR <10 mL/min: 50 mg daily	- Anaemia due to pure red cell aplasia (rare).
Emtricitabine (FTC)	200 mg daily	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.	- Palmar hyperpigmentation. - Anaemia due to pure red cell aplasia (rare). LoE:IVb^xix
Tenofovir alafenamide (TAF)	25 mg daily If coformulated 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 - Fanconi syndrome - Reduced bone mineral density

Class NNRTI:

Generic name

Usual dose

Renal adjusted dose

Important adverse drug reactions (ADRs) and timing

Efavirenz (EFV)

600 mg at night

Dose adjustment not required

- 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)
LoE:IVb^xx

- Rash (1 to 6 weeks).
- Hepatitis (weeks to months)
- Gynaecomastia.

Class Boosted PI:

Generic name	Usual dose	Renal adjusted dose	Important adverse drug reactions (ADRs) and timing
Lopinavir/ ritonavir (LPV/r	400/100 mg 12 hourly OR 800/200 mg daily (only if PI-naïve)	Dose adjustment not required	- Gastrointestinal upset. - Dyslipidaemia (weeks). - Rash and/or Hepatitis (1 to 6 weeks).
Atazanavir/ ritonavir (ATV/r)	ATV 300 mg with ritonavir 100 mg daily	Dose adjustment not required	- Unconjugated hyperbilirubinaemia (common, but benign). - Dyslipidaemia (low risk). - Hepatitis (rare - 1 to 6 weeks). - Renal stones (uncommon).

Class InSTIs:

Generic name	Usual dose	Renal adjusted dose	Important adverse drug reactions (ADRs) and timing
Dolutegravir (DTG)	50 mg once daily	Dose adjustment not required	- 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.

Table 2: Dosing and important adverse effects associated with ART

The time-onset information with respect to adverse drug reactions (ADRs) serves as an estimate. Patients may present with ADRs with the onset deviating from that indicated in the table.

LoE:IIIb^xxi

ART: DRUG-DRUG INTERACTIONS

Information can be accessed from:

https://www.hiv-druginteractionslite.org/checker
http://www.mic.uct.ac.za/ and download the ARV/EML interaction checker.
Package inserts.

ART INTERACTIONS WITH RIFAMPICIN AND RECOMMENDATIONS FOR ADMINISTRATION

Class	ARV	Interaction with rifampicin	Dose of ARV with rifampicin
NRTI	3TC/FTC/TDF/ AZT/ABC	No clinically significant pharmacokinetic interactions	No dose adjustment required.
NNRTI	EFV	Non-significant change (EFV concentrations may increase in patients who are genetic slow metabolisers of EFV and are on isoniazid which also inhibits EFV metabolism).	No dose adjustment required (600 mg at night).
PI	LPV/r	LPV plasma concentrations significantly decreased	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. Dose should be gradually titrated upward over 1-2 weeks. Adjusted dose should be continued for 2 weeks after rifampicin is stopped.
PI	All other PIs	Marked reduction in PI concentrations	Do not prescribe concomitantly – replace rifampicin with rifabutin 150 mg daily (see monitoring instructions below).
InSTI	DTG	Significant reduction in concentration of DTG	Dose increased to 50 mg 12 hourly.*

Table 3: ART interactions with rifampicin and dose-adjustment recommendations

LoE:IIIb^xxii

In patients on atazanavir or darunavir, or if double dose LPV/r is not tolerated, replace rifampicin with:

Rifabutin, oral, 150 mg daily.
- Monitor FBC monthly for anaemia and neutropenia.
- Monitor clinically for symptoms of uveitis (e.g. pain, photophobia, variable loss of vision, circumcilliary injection, a miotic pupil) – immediately stop rifabutin pending ophthalmology opinion.

LoE:IIIb^xxiii

DRUG INTERACTIONS WITH DOLUTEGRAVIR

Interacting medicine	Effect of coadministration	Recommendation
Preparations containing polyvalent cations (Mg²⁺ , Ca²⁺, Fe²⁺, Al³⁺, Zn²⁺) Antacids Sucralfate Mineral supplements	Significant reduction in concentration of DTG	Magnesium- and aluminum-containing preparations should be taken 6 hours before or 2 hours after DTG. Calcium- and iron- containing preparations can be taken with DTG together with food. Note: Iron and calcium should be taken at least 4 hours apart from one another
Anticonvulsants: Carbamazepine Phenobarbital Phenytoin	Significant reduction in concentration of DTG	Avoid co-administration if possible. Consider valproate or lamotrigine. For carbamazepine: Double DTG dose to 50 mg 12 hourly.
Metformin	May increase metformin concentration	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. See Appendix II for further guidance on patients with renal impairment.
Rifampicin	Significant reduction in concentration of DTG	Double DTG dose to 50 mg 12 hourly.

Table 4: Drug interactions with DTG

LoE:IIIb^xxiv

DRUG INTERACTIONS WITH BOOSTED PIs

Interacting medicine	Effect of coadministration	Recommendation
Substrates of cytochrome P450 3A4 (e.g. most statins, calcium channel blockers, most SSRIs, most benzodiazepines)	Significant increase in levels of CYP3A4 substrates	Avoid co-administration or use lower doses of CYP3A4 substrates (always consult interaction resources).
Anticonvulsants: Carbamazepine Phenobarbital Phenytoin	Significant reduction in concentration of PI	Avoid co-administration. Consider valproate or lamotrigine.
Proton pump inhibitors	Significant reduction in ATV levels	Avoid co-administration. LoE:IIIb^xxv
Rifampicin	Significant reduction in levels of PI	Double LPV/r dose. Avoid co-administration of other PIs (replace rifampicin with rifabutin)

Table 5: Drug interactions with boosted PIs

MONITORING ON ART

Baseline evaluation

- Confirm HIV positive result with second test.
- WHO staging.
- Check CD4 count.

LoE:IVb^xxv

If CD4 <200 cells/mm³ :

- Check cryptococcal antigen (if positive, perform LP regardless of whether symptoms are present or not).
- Initiate cotrimoxazole prophylaxis (See Cotrimoxazole prophylaxis in Opportunistic diseases).
- Reflex CrAg testing is done on the CD4 sample if CD4 <100 cells/mm3 . If patient’s CD4 is 100-199, a serum CrAg test must be ordered separately.

- 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).

LoE:IIIb^xxvi

- Haemoglobin
- Check HBsAg (if positive, TDF should form part of the regimen).
- Cervical cancer screening

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

LoE:IIb^xxviii

On ART

- 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/recommenced. 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.

Table 6: Monitoring on ART

HIV VIRAL LOAD MONITORING SCHEDULE

Click on image to enlarge.

DC: Dispensing cycle; MMD: Multi-month dispensing; RPCs: Repeat prescription collection strategies

Figure 1: Incorporated from the NDoH 2023 ART Clinical Guidelines for the Management of HIV in Adults, Pregnancy and Breastfeeding, Adolescents, Children, Infants and Neonates.

See 10.1.1 Management of selected antiretroviral adverse drug reactions

See 10.1.2 Immune reconstitution inflammatory syndrome (IRIS)

Click here to access the pdf.

Standard Treatment Guidelines and Essential Medicines List for South Africa, Adult Hospital Level, 2020-2024_Version 2.1_09 December 2024

Chapter 10 HIV and AIDS_10.1 Antiretroviral Therapy

Antiretroviral Therapy