OpiniãoRecommendation 8.
It is recommended that TB patients who are living with HIV should receive at least the same duration of daily TB treatment as HIV-negative TB patients (strong recommendation, high certainty of evidence)
Source of recommendation
This recommendation was first put forward in 2010 and considered valid in the guidelines update of 2017 (see mapping of recommendations in Annex). The recommendation is copied without modification into this consolidated document and appears exactly as in the 2010 guidelines.
Justification and evidence
A systematic review and meta-analysis of 6 randomized controlled trials and 21 cohort studies provided pooled estimates of failure, relapse and death by duration of rifampicin, and daily intensive phase versus intermittent throughout [40]. The systematic review revealed a marked and significant reduction in failure and relapse in the arms where some or all patients received ART. In a regression model, treatment failure or relapse was 1.8-2.5 times more likely with intermittent rather than daily dosing in the intensive phase. Compared with 8 or more months of rifampicin, 2-month rifampicin regimens carried a 3-fold higher risk of relapse and 6-month regimens carried a 2.2 -fold higher risk. Extending treatment beyond 6 months is recommended by some expert groups in certain persons living with HIV and the meta-analysis showed that this is associated with significantly lower relapse rates. However, several other considerations were given greater weight. Separate regimens for TB patients living with or without HIV would be very challenging in operational terms and could create stigma. Other potential harms of extending treatment are acquired resistance to rifampicin, and a longer period during which ART options are limited (because of ART-rifampicin interactions).
Recommendation 9.
ART should be started as soon as possible within two weeks of initiating TB treatment, regardless of CD4 cell count, among people living with HIV.ᵃ
Adults and adolescents (strong recommendation, low to moderate certainty of evidence;
Children and infants (strong recommendation, very low certainty of evidence)
ᵃ. Except when signs and symptoms of meningitis are present.
Source of recommendation
This recommendation is from WHO's Consolidated guidelines on HIV infection, testing, treatment, service delivery and monitoring: recommendations for a public health approach [41]. The background and history of this recommendation is provided below, while the detailed rationale and supporting evidence can be found in the source document.
The recommendation applies to both children and adults but the strength of the recommendation and certainty of the evidence differ for each group because of the difference in the available data for the reviews. One specific exception that is highlighted in this recommendation relates to situations in which signs and symptoms of meningitis are present. Caution is needed regarding people who are living with HIV and who have TB meningitis because immediate ART is significantly associated with more severe adverse events. Thus, it might be a consideration to delay ART for 4-8 weeks after TB treatment is initiated in such situations.
The use of corticosteroids as adjuvant treatment for TB meningitis still applies in these situations.
Background
Since 2010, WHO has recommended that ART be started as soon as possible within eight weeks of initiating TB treatment (strong recommendation, high certainty of evidence) [42]. In 2012, WHO added a recommendation to initiate ART within two weeks among those with a CD4 count less than or equal to 50 cells/mm³ (except for children for whom previous recommendations remained unchanged because of the lack of specific evidence) [43]. In 2017, on the basis of a systematic review of evidence that earlier ART initiation resulted in reduced morbidity and mortality [44], WHO recommended offering rapid ART initiation within one week, and on the same day if ready, for all people diagnosed with HIV - including adults, adolescents and children [44] - with stated cautions for those with signs and symptoms of TB meningitis.