⚙ Key Principle: Virological failure is defined as VL > 1000 copies/mL on two consecutive measurements 3 months apart, after at least 6 months on ART, with documented adherence support.
1. Failed First-Line Regimen
2. Failure Confirmation
3. Adherence Assessment
4. Current Parameters
Assessment Result📚 Drug Pearls
⚙ Types of Treatment Failure
Type
Definition
Preferred Metric
Virological
VL > 1000 copies/mL on 2 consecutive samples 3 months apart, after ≥ 6 months on ART
Gold standard. Primary trigger for switch.
Immunological
CD4 falls to (or below) pre-ART level, or persistent CD4 < 100 after 6 months, or 50% fall from peak
Less reliable. May lag 6 to 12 months behind VL failure.
Clinical
New or recurrent WHO Stage 4 event after 6 months on ART
Least reliable. Must exclude IRIS. Only use if VL is unavailable.
Adherence Assessment Before Switch
NACO mandates adherence counselling before any regimen switch. A confirmed unsuppressed VL with poor adherence should trigger intensive adherence support for 3 months, followed by a repeat VL. Only if VL remains > 1000 despite good adherence should the switch occur. Premature switching in the setting of poor adherence risks wasting the second-line regimen.
Second-Line Drug Pearls
ATV/r (Atazanavir/Ritonavir 300/100mg OD): Preferred PI. Causes unconjugated hyperbilirubinaemia (scleral icterus) in up to 40% — cosmetically distressing but clinically benign. Avoid with PPIs (drastically reduces ATV absorption). Take with food.
LPV/r (Lopinavir/Ritonavir 200/50mg, 2 tabs BD): Alternative PI. GI side effects (diarrhoea, nausea) are common and may limit adherence. Heat-stable tablets preferred over syrup. Significant metabolic effects (dyslipidaemia, insulin resistance).
Third-Line ART: Available only at designated ART Plus centres. Regimen: DRV/r 600/100mg BD + optimised backbone + RAL 400mg BD or DTG 50mg BD. Requires specialist review and often genotypic resistance testing.
