Table 3.

Regimens for treating DR-TB and HIV components in patients with established coinfection

Regimens for DR-TB component	Regimens for HIV component
Isoniazid (H) mono/polydrug resistance WHO 2016 IP (3–6 months): Lfx + Km + R + E + Z CP (6 months): Lfx + R + E + Z WHO 2019 All oral regimen (6 months): Lfx + R + E + Z (No IP or CP) If Lfx cannot be used (9 months): high-dose Mfx + R + E + Z If high-dose Mfx or Z cannot be used, replace with Lzd; if not Lzd, replace with Cfz; if not Lzd + Cfz, add Cs Neither high-dose Mfx nor Z can be used (9 months): add two of three in order of preference — Lzd, Cfz, Cs MDR-TB/RR-TB (longer or conventional) WHO 2016 IP (6–9 months): Lfx + Km + Eto or Pto + Cs or Tzd + Z + E CP (18 months): Lfx + Eto or Pto + Cs or Tzd + E (Also used in trials: STREAM and TB PRACTECAL trials — regimen A; End TB — regimen F) All-oral regimen (18–20 months; 6 months): Bdq+ Lfx + Lzd + Cfz + Cs (no IP or CP) WHO 2019 Abovementioned all-oral regimen preferred	First-line regimens (WHO-approved) Adults Two NRTIs + NNRTI or integrase inhibitor TDF + 3TC or FTC + Efv 600 mg/day in FDC (preferred combination) Alternative combination if above drugs contraindicated or not available: Azt + 3TC or FTC + Efv 600 mg/day Azt + 3TC or FTC + Nvp TDF + 3TC or FTC + Nvp Abc + 3TC or FTC + Efv 600 mg/day Abc + 3TC or FTC + Nvp TDF + 3TC or FTC + Dtg or Ral (better toxicity profile or less interaction with second-line drugs) TDF + 3TC or FTC + Efv 400 mg/day D4T should be avoided Children 3–10 years of age Abc + 3TC + Efv (preferably) or Nvp Azt or TDF + 3TC or FTC + Efv (preferably) or Nvp
Modification in initial 6 months If Lfx cannot be used, replace with high-dose Mfx If high-dose Mfx cannot be used, replace with Dlm If high-dose Mfx and Dlm cannot be used, addition of two drugs from replacement sequence containing group C drugs in order Z, Am, Eto, PAS, E, Imp-Cln or Mpm, Amx-Clv If Bdq cannot be used, replace with Dlm If Dlm cannot be used, addition of two drugs from replacement sequence containing group C drugs If one of Lzd, Cfz, or Cs cannot be used, no replacement if Bdq and Lfx/high-dose Mfx can be given If two or three of Lzd, Cfz, or Cs cannot be used, replace with two drugs from replacement sequence If three of five drugs from regimen cannot be used, replace with three drugs from replacement sequence Modification after 6 months If no drug (Lfx, Lzd, Cfz, Cs) can be used, no replacement If two drugs cannot be used, replace with two drugs from replacement sequence	Children ≤3 years of age Abc or Azt + 3TC + LVP/r (preferred) or Nvp Abc + 3TC + Azt (preferred in case of HIV and TB coinfection) Second-line regimens (WHO-approved) Indicated when first-line regimens ineffective or fail, as detected by CD4 count or virological load Adults Two NRTIs + boosted PI If first-line regimen contains TDF: (Azt or Abc) + 3TC + Lpv/r or Atv/r or Drv/r If first-line regimen contains Azt or d4T: TDF + 3TC or FTC + Lpv/r or Atv/r or Drv/r Alternative regimen Dtg or Ral + Lpv/r Children up to 10 years of age If first-line regimen contains Abc or TDF: Azt + 3TC or FTC If first-line regimen contains Azt or D4T: (Abc or TDF) + 3TC or FTC If first-line regimen contains Lpv/r: Ral If first-line regimen contains Efv or Nvp: Lpv/r or Atv/r
MDR-TB with additional FQ resistance (pre-XDR-TB) IP (6–9 months): Mfx + Km + Eto or Pto + Cs or Tzd + Z + Lzd + Cfz CP (18 months): Mfx + Eto or Pto + Cs or Tzd + Lzd + Cfz Regimen containing newer drug Bdq IP (6–9 months): Km + Eto or Pto + Cs or Tzd + Z + Lzd + Cfz + (6 months) Bdq CP: (18 months): Eto or Pto + Cs or Tzd + Lzd + Cfz MDR-TB with additional SLID resistance (pre-XDR-TB) IP (6–9 months): Lfx + Cm + Eto or Pto + Cs or Tzd + Z + Lzd + Cfz CP (18 months): Lfx + Eto or Pto + Cs or Tzd + Lzd Regimen containing newer drug Bdq IP (6–9 months): Lfx + Cm + Eto or Pto + Cs or Tzd + Z + Lzd + Cfz + (6 months) Bdq CP (18 months): Lfx + Eto or Pto + Cs or Tzd + Lzd XDR-TB IP (6–9 months): Mfx + Cm + Eto or Pto + Cs or Tzd + Z + Lzd + Cfz + E CP (18 months): Mfx + Eto or Pto + Cs or Tzd + Lzd + Cfz + E Regimen containing newer drug Bdq IP (6–9 months): Cm + Eto or Pto + Cs or Tzd + Z + Lzd + Cfz + E + 6 months Bdq CP (18 months): Eto or Pto + Cs or Tzd + Lzd + E	Important considerations for using ART Efv preferred over Nvp, as potential hepatotoxicity of Nvp with anti-TB therapy If patient already on Nvp-based ART, then switch to Efv once anti-TB medication started and to be continued TDF should be avoided in cases of nephrotoxicity In cases of H-monoresistant or poly-DR-TB: R to be substituted with rifabutin or rifapentine if patient is on PI or integrase inhibitor–based ART Dosage of integrase inhibitor to be doubled If a patient is on Bdq-based regimen, TDF, Azt, Nvp, or Dtg preferred over Efv or PI No interaction with Dlm-based regimen
Shorter regimens for M/XDR-TB WHO-approved STREAM 1 (regimen B) IP (4–6 months): Km/Am + high-dose H + Eto or Pto + Mfx or Gfx + Cfz + E + Z CP (5 months): Mfx or Gfx + Cfz + E +Z Ongoing trials with proposed regimens (yet to be approved) MDR-TB STREAM 2 (regimen C) IP (4 months): high-dose H + Pto + Bdq + Lfx + Cfz + E + Z CP (6 months): Bdq + Lfx + Cfz + E + Z STREAM 2 (Regimen D) IP – (2 months)- Km + High dose H + Bdq + Lfx + Cfz + Z CP- (4–5 months)- Bdq + Lfx + Cfz + Z End TB Regimen A (9 months): Bdq + Lzd + Mfx + Z Regimen B (9 months): Bdq + Lzd + Cfz + Lfx + Z Regimen C (9 months): Bdq + Dlm + Lzd + Lfx + Z Regimen D (9 months): Dlm + Cfz + Lzd + Lfx + Z Regimen E (9 months): Dlm + Cfz + Mfx + Z
NeXT 6–9 months: Bdq + Lzd + Lfx or Mfx + Eto or Pto/high-dose H + Z MDR-END 9–12 months: Dlm + Lzd + Lfx or Mfx + Z STAND 6 months: Mfx + Ptm + Z 6 months: Bdq + Mfx + Ptm + Z SimpliciTB 6 months: Bdq + Ptm + Mfx + Z NIX (XDR-TB) 6–9 months: Bdq + Ptm + Lzd TB PRACTECAL (M/XDR-TB) Regimen B (6 months): Bdq + Ptm + Lzd + Mfx Regimen C (6 months): Bdq + Ptm + Lzd + Cfz Regimen D (6 months): Bdq + Ptm + Lzd BEAT (pre-XDR-TB and XDR-TB) 6–9 months: Bdq + Dlm+ Lzd + Cfz

Note: Regimens can be modified further based on grouping of drugs recommended by WHO if there is documented resistance or intolerance to any of these drugs.