تعليقRecommendation 6.1 Starting ART
Justification and evidence
The recommendation in this section addresses one PICO question:
PICO question (DR-TB, 2011): In patients with HIV infection and drug-resistant TB receiving antiretroviral therapy, is the use of drugs with overlapping and potentially additive toxicities, compared with their avoidance, more or less likely to lead to cure or other outcomes?⁵⁹
Evidence was reviewed from 10 studies (123–132), to assess patient treatment outcomes when ART and second-line antituberculosis drugs were used together. None of the data were from RCTs. IPD were available for 217 patients with DR-TB, of whom 127 received ART. The level of evidence in individual observational studies varied from low to very low quality.
Summary of findings
The pooled IPD from longitudinal cohort studies showed a lower risk of death and a higher likelihood of cure, and resolution of TB signs and symptoms in patients using ART, compared with those not using ART (low-quality evidence). There is very low certainty evidence for other outcomes that were considered critical or important for decision-making (e.g. severe adverse effects from secondline drugs for DR-TB, occurrence of sputum smear or culture conversion, interactions of ART with antituberculosis drugs and default from treatment). Available data did not allow assessment for several other outcomes of interest; namely, avoiding the acquisition of additional drug resistance, preventing TB transmission, sustaining relapse-free cure, establishing the optimal duration of MDR-TB treatment, avoiding unnecessary MDR-TB treatment, reducing costs and improving population access to appropriate care.
Benefits
The strong recommendation for the use of ART is based in part on indirect evidence from its use in any patient with active TB, which shows large beneficial effects and a very high mortality when ART is not employed (133) particularly in highly immunocompromised patients (CD4 cell count <50 cells/mm3 ) (134, 135). In the absence of other data specific to patients with DR-TB receiving second-line antituberculosis medication, the decision on when to start ART should be no different from the approach to a patient living with HIV with drug-susceptible TB. ART should thus be initiated regardless of CD4 cell count and as soon as antituberculosis treatment is tolerated, ideally as early as 2 weeks and no later than 8 weeks after initiation of antituberculosis treatment (133, 136). However, for TB patients living with HIV with profound immunosuppression (e.g. CD4 counts <50 cells/mm3 ), they should receive ART within the first 2 weeks of initiating TB treatment (110).
Risks
The successful implementation of this recommendation will depend on the availability of more providers trained specifically in the care of HIV and DR-TB, and drug–drug interactions. A substantial increase in the availability of and patient’s access to treatment, and additional support for ensuring adherence would probably be needed. The need for increased integration of HIV and TB care for effective patient management, prompt evaluation of adverse events and case-holding throughout treatment will necessitate more resources. Updated information on drug–drug interactions between antiretroviral and antituberculosis medicines is now available online (44).
Values and preferences
A high value was placed on outcomes such as prevention of early death and TB transmission, and a lower value was placed on the resources required to make ART available to all MDR-TB patients infected with HIV.
59 The outcomes considered for this question comprised: 1. Cure (treatment failure), 2. Prompt initiation of appropriate treatment, 3. Avoiding the acquisition or amplification of drug resistance, 4. Survival (death from TB), 5. Staying disease-free after treatment; sustaining a cure (relapse), 6. Case-holding so the TB patient remains adherent to treatment (default or treatment interruption due to non-adherence), 7. Population coverage or access to appropriate treatment of DR-TB, 8. Smear or culture conversion during treatment, 9. Accelerated detection of drug resistance, 10. Avoidance of unnecessary MDR-TB treatment, 11. Population coverage or access to diagnosis of DR-TB, 12. Prevention or interruption of transmission of DR-TB to other people, including other patients and health care workers, 13. Shortest possible duration of treatment, 14. Avoiding toxicity and adverse reactions from antituberculosis drugs, 15. Cost to the patient, including direct medical costs and other costs such as transportation and lost wages due to disability, 16. Resolution of TB signs and symptoms; ability to resume usual life activities, 17. Interaction of antituberculosis drugs with non-TB medications, and 18. Cost to the TB control programme.