Why dolutegravir is now first-line
Dolutegravir (DTG) is an integrase strand-transfer inhibitor (INSTI). It blocks the integration of HIV DNA into the host cell genome. DTG has replaced earlier regimens in most international guidelines because of its high barrier to resistance, once-daily dosing, minimal drug interactions, and tolerability.
Standard regimen
Most first-line regimens combine dolutegravir with two NRTIs — most commonly tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC) or emtricitabine (FTC). The combination is often available as a single fixed-dose tablet taken once daily.
First 4 weeks
Viral load should begin falling rapidly — typically a 1–2 log reduction in the first month. Some patients experience mild headache, fatigue, or insomnia in the first 2–4 weeks. These generally resolve without intervention. Neuropsychiatric effects (sleep disturbance, vivid dreams) affect a minority and are more common in patients with underlying mental health conditions.
Week 4–12
Most patients reach an undetectable viral load (<50 copies/mL) within 12–24 weeks. CD4 count begins rising. Adherence is critical in this phase — missing doses increases the risk of resistance development, though DTG’s high barrier means the risk is lower than with first-generation regimens.
Monitoring
Typical monitoring includes viral load and CD4 at baseline, 4 weeks, 12 weeks, then every 3–6 months once stable. Renal function and bone density monitoring are recommended for TDF-containing regimens. DTG can increase serum creatinine slightly by inhibiting tubular secretion — this is not a sign of renal damage.