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ART timing with Opportunistic Infections

For a comprehensive discussion of the treatment of opportunistic infections, please see current DHHS guidelines [1]

Here we discuss only the impact of opportunistic infection on the timing and selection of ART regimens.

Opportunistic Infection Timing Considerations Other Notes
Tuberculosis (TB)

Current guidelines state:

"All HIV-infected patients with active TB who are not on ART should be started on ART as described below:

CD4<50: Initiate ART as soon as possible, but within 2 weeks (Note there may be higher rates of IRIS, but this group has been shown to have mortality benefit with earlier initiation.

CD4>=50: Initiate ART within 8 weeks of starting TB treatment

*Use caution with TB meningitis, since IRIS can have more serious adverse consequences/deathOn the basis of clinical trials (SAPIT), it is NOT recommended to delay ART until the end of TB treatment.  Early treatment is associated with 56% lower mortality, than sequential therapy.

Several additional trials have provided insights into the timing of "early" ART initiation. In CAMELIA (661 patients in Cambodia with low median CD4 of 25), there was mortality benefit to starting ART within 2 weeks compared to waiting until 8 weeks.  In ACTG A5221, 809 patients (median CD4 77), there was not a mortality benefit when comparing 'immedaiate (within 2 weeks) to 'early' (8-12 weeks) ART initiation overall; but in those with CD4<50, mortality was reduced from 26.6% to 15.5% comparing the 'early' to 'immediate' ART arms, with increases in IRIS in the immediate ART arm. 

It is important to recognize the potential for drug-drug interactions, particularly with Rifamycins. 

When treating with Rifampin, some considerations include:

a)TAF is currently not recommended with rifamycins as a result of possible pgp induction that could impact TAF concentrations

b)Some INSTIs may be used but have drug-drug interactions and require increases in DTG and RAL doses; EVG cannot be used. DTG is increased to 50mg BID.  RAL is increased to 800mg BID

c)Should not be used with PI's, EVG/c, ETR, RPV, or TAF

d)standard doses of NRTIs, 

e)standard doses of EFV. European guidelines suggest therapeutic drug level monitoring because EFV concentrations are reduced. 

f)MVC does 600mg BID

When treating with Rifabutin, some considerations include:

a)Can be used with PI's but there is dosing adjustment of RBT if used with PI's: RBT is decreased to 150mg QD.  PI's/r are standard dose. 

b)TAF is currently not recommended with rifamycins as a result of possible pgp induction that could impact TAF concentrations

c)DTG and RAL can be used without dosing adjustment

d)RBT reduces EVG/c decreases EVG Cmin by 67% and coadministration is not recommended. European SPC recommends that if combination is needed, to use RBT 150 three times/week. EACS guidelnes suggest that EVG/c can be used at standard doses with RBT 150mg QD

e)MVC: standard dose of MVC (300mg BID in absence of PI, 150mg BID in presence of PI)

f)NRTI: standard dose of all NRTI's

g)NNRTI: Consdider RBT 450mg QD if given with EFV (EFV standard doses); ETV can be used at standard doses of both RBT and ETV; NVP should not be used; RPV dose should be increased.