Clinical
South African HIV Guidelines
Last reviewed 26 May 2026
The 2026 National Consolidated Guidelines for the Prevention and Management of HIV (NCG 2026) are the National Department of Health document that merged the previously separate ART, PMTCT and Advanced HIV Disease guidelines into a single programme reference. They signpost to the standalone documents the NCG defers to (PrEP 2021, PEP 2019, the Lenacapavir-PrEP 2025 guideline, the AHD service-delivery package).
What’s new in the 2026 NCG
The 2026 consolidation introduces genuine change across the programme, the section with the most change since the previous guidelines. The deltas, grouped:
Terminology.
- “First / second / third line” replaced by TLD 1 / TLD 2 / TLD 3 in adults, and ALD 1/2/3 in children. The terminology emphasises that dolutegravir is the unifying anchor.
- “Month” replaced by dispensing cycle (DC): one DC is 28 or 30 days.
First-line and switching.
- TDF weight threshold dropped from 35 kg to 30 kg. All clients 30 kg or more and 10 years or older are now eligible for TLD.
- TDF recycling is permitted: TLD can be re-used as second-line (TLD 2) after TDF-containing first-line failure, because dolutegravir’s high barrier and M184V’s partial re-sensitisation effect together preserve useful NRTI (nucleoside reverse transcriptase inhibitor) activity.
- Abacavir replaces zidovudine as the preferred TDF alternative.
- AZT is no longer in any standard adult regimen: reserved for renal failure with concurrent ABC hypersensitivity, or the preterm neonate.
- Atazanavir/ritonavir replaces lopinavir/ritonavir as the preferred PI (protease inhibitor) when one is needed (LPV/r retained for rifampicin co-treatment).
- Switching from TEE to TLD is viral-load-independent.
Paediatrics.
- Dolutegravir dispersible (DTG 10 mg DT) usable from 2 kg or more and 37 weeks gestational age or more.
- New ALD fixed-dose combination (ABC/3TC/DTG 600/300/50) for 25 kg or more, and paediatric pALD 60/30/5 mg for neonates from 2 kg.
- The 10 mg dispersible is not bioequivalent to a 10 mg film-coated tablet (50 mg film = 30 mg dispersible).
Monitoring.
- First viral load moved from 6 months to 3 dispensing cycles (about 3 months). The eGFR/creatinine check follows the new VL timing.
- Subsequent VLs: 10 DCs, then 22 DCs, then every 12 DCs (annual). Breastfeeding women six-monthly.
- Virological failure redefined: two consecutive viral loads at or above 1,000 copies/mL, after at least 9 months on a DTG-containing regimen, with at least two documented adherence interventions.
- Reflex dolutegravir drug-level testing as the national gatekeeper before resistance genotyping (covered below).
- No regimen change off a DTG-based regimen without a confirmed integrase resistance mutation, clinician/ADReC oversight required.
Testing services.
- Three-test rapid algorithm retained; routine retesting becomes annual rather than at any window period.
- HIV self-screening (HIVSS) standardised as an entry test, including for PEP follow-up, PrEP continuation from the second visit, PrEP re-engagement and index/social-network testing.
- Index testing expanded to all viraemic clients, re-engagers, all biological children under 19 years, and the wider social networks of key populations.
PMTCT and infants.
- Higher-risk infant threshold dropped from maternal VL 1,000 or above to 50 copies/mL or above. This single change extends extended dual prophylaxis to a much larger fraction of HIV-exposed infants.
- All HIV-exposed infants now receive dual NVP + AZT prophylaxis at birth until the delivery viral load is known.
- Cotrimoxazole withdrawn from HIV-exposed uninfected infants; reserved for confirmed HIV infection.
- TPT (tuberculosis preventive therapy) in pregnancy indicated only if the woman has AHD (CD4 at or below 200 or WHO stage 3/4).
Programmatic.
- Time-on-ART removed as a repeat-prescription-collection eligibility criterion. Clients move into RPC as soon as the first VL is suppressed.
- Facility-provided 6-month multi-month dispensing (6MMD) introduced for very stable TLD clients.
- 3MMD opened to previously excluded groups: children from six months, postnatal women, TB co-infected, elevated VL or re-engaging clients.
- A differentiated re-engagement algorithm for clients returning to care after disengagement.
Integration and prevention.
- TB, EPI (Expanded Programme on Immunisation), family-planning and NCD (non-communicable disease) schedules are structurally aligned with the ART scripting cycle.
- Syphilis testing intensified through ANC (antenatal care); syphilis-related stillbirths now notifiable.
- The Lenacapavir-PrEP 2025 standalone guideline is explicitly referenced; the NCG retains only a summary PrEP/PEP position and points readers to the dedicated documents.
Diagnosis and the testing pathway
HIV testing in the South African public sector is governed by the 5Cs:
- Consent: testing requires informed consent.
- Confidentiality: results are confidential and disclosed only with consent.
- Counselling: pre- and post-test counselling.
- Correct test results: high-quality testing through validated algorithms.
- Connection to care: every positive result is linked to ART initiation and ongoing care.
Consent in children. Any child of 12 years or older can self-consent to HIV testing. A child under 12 who has sufficient maturity to understand the test can also self-consent (the “mature minor” framework of the Children’s Act). A child under 12 without that capacity requires caregiver/designated-adult consent.
The serial three-test rapid algorithm. A reactive screening rapid test is confirmed by a different rapid test, and if those agree the result is reported. A third rapid test (or laboratory ELISA, enzyme-linked immunosorbent assay) is used when the first two are discrepant. The algorithm preserves a positive predictive value of 99% or above in low-prevalence settings.
Tests by age. Children under 18 months are tested by HIV PCR (a positive screening PCR requires a confirmatory PCR or viral load). Children 18 months to 2 years are tested by rapid screen with PCR confirmation. Children over 2 years and adults use the three rapid-test algorithm. HIV self-screening (HIVSS) is an optional first step from 12 years.
Retesting cadence. Routine retesting is annual; the previous window-period retesting is retained only for sexual violence (6 and 12 weeks), occupational exposure (6 and 12 weeks) and acute viral syndrome (6 weeks).
Confirmation in children under 2 years. A viral load may substitute for the confirmatory PCR after a positive screening PCR, giving a baseline VL in parallel. ART is initiated without waiting for the confirmatory result.
ART initiation and the TLD framework
Universal eligibility. All people living with HIV are eligible for ART regardless of CD4 count or WHO clinical stage. Initiation is within 7 days of diagnosis, same-day where possible, with pregnant women, children under 5 and AHD prioritised. Counselling and OI (opportunistic infection) screening occur at initiation, not as a delaying step.
Indications to defer. ART is deferred (briefly) where intercurrent illness or specific opportunistic infections demand it:
- TB meningitis (drug-sensitive or DR-TB): defer ART 4 to 8 weeks.
- Cryptococcal meningitis: defer ART 4 to 6 weeks after starting antifungals.
- DS-TB extra-neurological: CD4 below 50, start ART within 2 weeks; CD4 at or above 50, start at 8 weeks.
- DR-TB extra-neurological: start ART at 2 weeks.
- Asymptomatic CrAg-positive with negative LP: start ART immediately alongside pre-emptive fluconazole.
- Acute bacterial pneumonia or PJP (Pneumocystis jirovecii pneumonia): defer 1 to 2 weeks.
Established ART is never interrupted on diagnosis of one of these conditions; deferral applies only to fresh initiation.
The TLD 1 / TLD 2 / TLD 3 framework. The 2026 NCG categorises every patient on TLD by the trajectory that brought them there:
- TLD 1. ART-naïve patients started on a DTG-based regimen, OR patients switched from a non-DTG first-line regimen (typically TEE) with a documented viral load below 50 copies/mL in the last 12 months.
- TLD 2. Patients switched from a non-DTG first-line regimen with a viral load at or above 50, OR patients switched from a PI-based second-line regimen with a recent viral load below 50, OR patients switched from a PI-based second-line with VL at or above 1,000 without a genotypic test (no PI resistance assumed).
- TLD 3. Patients switched to a third-line dolutegravir regimen on the basis of a genotypic resistance test showing PI resistance in a previous second-line, accessed through ADReC (the ARV Drug Resistance Committee, the renamed TLART).
The TDF recycling principle underpins the logic: because dolutegravir’s genetic barrier is high and the M184V mutation (which almost always accompanies first-line TLD failure) partially re-sensitises virus to tenofovir, TLD can serve as both first-line and second-line for a single patient. The dominant determinant of outcome on TLD 2 is therefore adherence, not resistance.
Monitoring on ART
Viral load schedule:
- First VL at 3 dispensing cycles after ART start (about 3 months).
- Second VL at 10 DCs (around 10 to 12 months).
- Third VL at 22 DCs (around 24 months).
- Thereafter annually (every 12 DCs).
- Breastfeeding women are tested every 6 DCs from delivery until 6 weeks after stopping breastfeeding.
- Suppression target: below 50 copies/mL.
Creatinine and eGFR (where TDF is part of the regimen) follow the VL timing: baseline, month 3, month 10 to 12, then annually. The threshold for TDF discontinuation is eGFR below 50 mL/min/1.73 m².
CD4 monitoring is no longer routine beyond baseline plus the 10 to 12 DC check. Repeat CD4 is indicated when the count is at or below 200 (every 6 months until above 200), at any new WHO stage 3 or 4 event, when the viral load is at or above 1,000 copies/mL, or in a re-engaging client.
Lipid monitoring applies only to clients on a PI regimen: total cholesterol and triglycerides at month 3, with a fasting sample if abnormal. Clients on TLD have no routine lipid requirement.
AZT users (the small residual cohort) need a full blood count at months 1 and 3.
Detectable viral load: blip, low-level viraemia and virological failure
The NCG treats any viral load at or above 50 copies/mL as actionable, but distinguishes three patterns.
A viral blip is a single transient detectable result that returns to suppressed at the next measurement. Blips are not formally defined in the NCG but are managed by ABCDE adherence review and a repeat VL; the repeat is almost always undetectable.
Persistent low-level viraemia (LLV) is two or more consecutive viral loads in the 50 to 999 copies/mL range. This warrants enhanced adherence counselling and a lowered threshold for drug-resistance testing if the patient meets “special circumstances” criteria.
Confirmed virological failure is two consecutive viral loads at or above 1,000 copies/mL, after at least 9 months on a DTG-containing regimen, with at least two documented adherence interventions. The threshold is the trigger for the reflex DTG drug-level workflow.
The ABCDE differential for any elevated viral load, applied in order before requesting a resistance test:
- Adherence: the dominant cause of detectable viraemia on TLD.
- Bugs: concurrent infection (TB, STIs, sexually transmitted infections, recent vaccination).
- Correct dose for weight (paediatric particularly).
- Drug interactions: rifampicin, anticonvulsants, polyvalent cations.
- Resistance: only after the others are excluded.
The reflex dolutegravir drug-level testing workflow. When the criteria above are met, two EDTA tubes are sent, one for VL and one for drug-resistance testing (DRT). The laboratory performs a dolutegravir drug-level test (DLT) on the DRT sample first. If DTG is undetectable, the patient is non-adherent and no genotype is performed: the result drives enhanced adherence counselling. Only when DTG is detectable and VL remains at or above 1,000 does the laboratory proceed with full genotyping (RT + protease + integrase).
The cardinal rule: no patient is switched off a DTG-based regimen without confirmed integrase resistance. Switches require expert or ADReC authorisation.
TB co-treatment
TB is the dominant opportunistic infection in South African HIV practice, and rifampicin is the dominant drug-interaction problem.
Dolutegravir + rifampicin. Rifampicin induces UGT1A1 and CYP3A4 and reduces dolutegravir exposure. The accepted SA practice is to add a second 50 mg dolutegravir tablet twelve hours after the TLD dose, continuing until two weeks after rifampicin ends.
ART timing. Once TB workup is complete and treatment started, ART follows on a schedule driven by CD4 count and TB site:
- Drug-sensitive TB, extra-neurological, CD4 below 50: ART within 2 weeks.
- Drug-sensitive TB, extra-neurological, CD4 at or above 50: ART at 8 weeks.
- Drug-resistant TB, extra-neurological: ART at 2 weeks.
- TB meningitis or tuberculoma (DS or DR): defer ART 4 to 8 weeks.
- Pregnant or breastfeeding women on TB treatment: ART within 2 weeks regardless of CD4 (defer 4 to 8 weeks if meningitis).
Cryptococcal meningitis has a separate deferral window: ART starts 4 to 6 weeks after antifungal initiation.
Rifabutin substitution. The NCG does not feature rifabutin as a routine substitution; the only mention is the re-challenge scenario where DRV/r or ATV/r must be retained despite TB treatment. In standard practice patients on a PI regimen are switched to DTG before TB treatment.
IRIS: paradoxical immune reconstitution inflammatory syndrome. Paradoxical TB IRIS occurs in around 18% of patients starting ART within 30 days of TB treatment, particularly with CD4 below 100. Diagnosis is one of exclusion (rule out MDR/XDR-TB and non-adherence). Treatment of established non-neurological IRIS is prednisone 1.5 mg/kg for 2 weeks then 0.75 mg/kg for 2 weeks. Prophylactic prednisone for high-risk patients (CD4 at or below 100 and TB treatment started fewer than 30 days before ART) is 40 mg daily for 2 weeks then 20 mg for 2 weeks.
Advanced HIV Disease
Definition. Any of:
- CD4 count at or below 200 cells/µL, or
- WHO clinical stage 3 or 4, or
- Children under 5 years (automatic AHD unless they have been stable on ART for at least 12 months).
The 2026 NCG distils AHD care into a nine-step approach:
- Identify the seriously ill through danger-sign screening.
- Identify high-risk groups: new HIV diagnosis; clinically unwell on or off ART; VL above 1,000 on ART; child under 5; re-engagers after a gap of more than 90 days.
- Assess and treat: CD4 with reflex serum CrAg below 200; screen for TB (including urine TB-LAM, lipoarabinomannan); investigate for severe bacterial infection and any WHO stage 3 or 4 event; if serum CrAg is positive, perform an LP.
- Prevent opportunistic infections: cotrimoxazole if eligible and tuberculosis preventive therapy if active TB is excluded.
- Provide ART: rapid initiation on a DTG-based regimen unless one of the specific deferral indications applies.
- Provide other care: mental health, NCDs, SRH (sexual and reproductive health), palliative.
- Adherence support: explicit IRIS counselling and side-effect review.
- Continuity of care between PHC (primary health care) and hospital: discharge plan and community-health-worker follow-up.
- Intensified follow-up: 2-weekly or monthly visits for the first 3 months and missed-appointment tracing.
Reflex CrAg and pre-emptive fluconazole. Any patient with CD4 at or below 200 gets a reflex serum CrAg. A positive serum CrAg with a negative CSF CrAg on LP is cryptococcal antigenaemia, treated with fluconazole 1,200 mg daily for 14 days as induction, then consolidation and maintenance until CD4 recovers above 200 on ART. Confirmed cryptococcal meningitis is treated with the single-dose liposomal amphotericin B regimen with flucytosine and fluconazole.
Urine TB-LAM is indicated for any PLHIV admitted to hospital, and for symptomatic outpatients with CD4 at or below 200 or AHD. A positive U-LAM gives clinical confirmation but no drug-susceptibility information: always do a parallel TB-NAAT (nucleic acid amplification test).
Cotrimoxazole prophylaxis (CPT). All HIV-positive infants under 1 year regardless of CD4 or stage; children 1 to 5 if CD4 at or below 25% or WHO 3/4; adults and children above 5 if CD4 at or below 200 or WHO 3/4. Stop once CD4 is above 200 (or above 25% in under-5s). CPT has been withdrawn from HIV-exposed but uninfected infants, a 2026 delta.
TPT. Adults and adolescents from 15 years receive INH (isoniazid) 300 mg with pyridoxine for 12 months (12H) as the default; 3HP (weekly INH plus rifapentine for 12 doses) is an alternative for clients 25 kg or more already on DTG with a recent suppressed VL, but not for new ART starters and not for PI-based regimens. TPT in pregnancy is indicated only if the woman has AHD.
PMTCT and Early Infant Diagnosis
The maternal regimen is TLD throughout pregnancy and breastfeeding. Women diagnosed in labour receive stat TLD plus stat single-dose nevirapine, then lifelong TLD from the next day, with contraception integrated into ANC and postnatal visits.
The 2026 stratification change. The previous “higher-risk” threshold of maternal viral load 1,000 copies/mL or above has been dropped to 50 copies/mL or above. The new categorisation:
- Maternal delivery VL below 50 copies/mL = LOW RISK. Stop AZT after birth; give nevirapine daily for 6 weeks.
- Maternal delivery VL at or above 50 copies/mL in a breastfeeding mother = HIGHER RISK. Continue AZT twice daily for 6 weeks and nevirapine daily for at least 12 weeks, until maternal VL is below 50, or until 4 weeks after breastfeeding stops.
- Maternal VL at or above 50 copies/mL with exclusive formula feeding. AZT for 6 weeks and NVP for 6 weeks.
At birth, before the maternal delivery VL is known, all HIV-exposed infants now receive the dual NVP+AZT regimen, another 2026 change.
The South African Early Infant Diagnosis algorithm. Test points:
- HIV PCR at birth.
- HIV PCR at 10 weeks (aligned with the EPI 10-week vaccination visit).
- HIV PCR at 6 months (aligned with the maternal 6-month VL).
- HIV antibody / rapid test at 18 months. Universal for all children regardless of HIV exposure status.
- Age-appropriate test 6 weeks after breastfeeding cessation.
- Any time the child is unwell.
A positive result in a child under 2 years requires confirmation on a fresh sample (or a baseline viral load) before reporting as infected.
Indeterminate HIV PCR management. Check the child’s prior test history:
- Prior PCR or VL positive or indeterminate: treat as HIV-infected, initiate ART, then confirm.
- Prior PCR negative or no prior test: repeat HIV PCR and viral load urgently. If the repeat PCR is positive or indeterminate, treat as infected. If the repeat is negative, return to routine HIV-exposed follow-up.
Abandoned infants are treated as HIV-exposed higher-risk: NVP for 6 weeks plus AZT for 6 weeks, with HIV PCR and rapid testing immediately, PCR at 10 weeks or 4 weeks after stopping NVP.
HIV and hepatitis co-infection
Baseline HBsAg (hepatitis B surface antigen) is checked in all newly diagnosed PLHIV. HBV is a notifiable medical condition; positive results should be notified to the NICD.
TDF dual coverage. Tenofovir is active against HBV. A patient on TLD who is HBsAg-positive is already on adequate HBV treatment: no additional anti-HBV therapy is required, and the HBsAg does not need to be rechecked. This is the routine SA scenario.
Never stop TDF abruptly. Discontinuing tenofovir, lamivudine or emtricitabine in an HBV-coinfected patient may precipitate a life-threatening hepatic flare. HBsAg must be checked before stopping any of these agents. If TDF must be replaced in a co-infected patient (eGFR 30 to 50), the substitute is TAF + FTC + DTG.
HBV vaccination of non-immune patients. Test HBsAb (hepatitis B surface antibody) if vaccination status is unknown. If HBsAb is 10 mIU/mL or above, the patient is immune, no action. Below 10, use a 3-dose schedule at 0/1/6 months. Recheck HBsAb 2 months after the last dose; if still below 10, repeat the 3-dose course; if still below 10, refer.
HCV is mentioned only briefly in the NCG: it progresses faster in HIV co-infection, and all-oral direct-acting antivirals (DAAs) achieve over 90% SVR (sustained virological response) regardless of HIV status. The HCV treatment specifics belong to the National Viral Hepatitis Guidelines.
PrEP and PEP: the national position
The NCG itself defers PrEP and PEP detail to standalone documents: PrEP 2021, PEP 2019, and the PrEP (Lenacapavir) 2025 guideline.
The NCG’s programmatic points:
- Every facility must offer PEP and PrEP. Antenatal clinics included.
- PEP is a 28-day course of TLD, started within 72 hours of a qualifying exposure (needle-stick injury, sexual assault, condom failure with a known HIV-positive partner). Start empirically.
- PrEP is offered to any HIV-negative person who requests it or is at substantial risk. After the first month a client transitions to 3MMD refills.
- HIV self-screening is acceptable as the test for PrEP continuation from the second visit, for re-engagement, and for PEP follow-up.
Adherence and differentiated care
A defining feature of the South African ART programme is differentiated care: moving stable clients out of frequent clinical visits into streamlined dispensing pathways while concentrating clinical effort on the unstable.
Stable client: most recent VL below 50; clinically well; no current opportunistic infection or uncontrolled NCD; not pregnant or within 12 months postpartum; over 5 years old.
Very stable client: meets the stable criteria plus at least 12 months on ART with two consecutive VLs below 50.
Repeat-Prescription Collection (RPC). Stable clients enter RPC as soon as the first VL is suppressed (the 2026 change; previously, a time-on-ART requirement applied). Options include facility pick-up points, adherence clubs and external pick-up.
Multi-month dispensing. 3MMD is available widely, including for groups previously excluded (children from 6 months, postnatal women, TB co-infected, elevated VL or re-engagers). 6MMD from the facility is a 2026 innovation for very stable clients on TLD.
Enhanced Adherence Counselling (EAC) is targeted at clients with adherence problems or virological non-response. It is not automatically required for clients whose only adherence barrier is logistical (offer MMD) or palatability (switch regimen).
Integration. Contraception, TPT and stable NCD treatment are integrated into the same six-monthly scripting cycle and the same MMD pick-up.
A brief note on consent, confidentiality and the healthcare worker question
The 2026 NCG addresses consent and confidentiality through the 5Cs framework woven into testing services (covered above), and through the clinical Disclosure SOP for children and adolescents in the annexures. It does not address HPCSA Rules on HIV-positive healthcare workers, restrictions on exposure-prone procedures, or detailed medico-legal responsibilities. These topics sit deliberately outside the NCG.
The relevant external sources:
- HPCSA Booklet 12, Ethical Guidelines for Good Practice with regard to HIV/AIDS: the canonical SA professional-ethics reference.
- National Institute for Occupational Health (NIOH) occupational HIV policy: for HCW workplace exposure management.
- PEP 2019 (National DoH): the operational PEP guideline.
These occupational-health and medico-legal topics sit outside the NCG and are covered by the external sources listed above.
References and recommended reading
- National Department of Health, South Africa. 2026 National Consolidated Guidelines for the Prevention and Management of HIV in Adults, Adolescents, Children, Infants and Pregnant and Breastfeeding Women. The primary source. 232 pages, six chapters plus annexures; the operational reference for South African HIV practice.
- Southern African HIV Clinicians Society. Adult Antiretroviral Therapy Guidelines, 2023 update. Useful clinician-society comparison, particularly on the preferred PI (DRV/r vs the NCG’s ATV/r), TAF positioning and routine baseline VL.
- National Department of Health. PrEP Guideline (2021), PEP Guideline (2019), and PrEP (Lenacapavir) Guideline (2025). The standalone documents the NCG defers to.
- HPCSA. Ethical Guidelines for Good Practice, Booklet 12: HIV/AIDS. For the medico-legal and HCW content the NCG does not address.
- THEMBISA, SANHANES and UNAIDS: the sources for the South African burden numbers the NCG does not publish itself.