Q: I have a patient with a low CD4 (<100) who has just presented. Since she is about to start a HAART regimen, should I wait until she has a good CD4 response before doing a TB skin test?

A: Rather than waiting, I would do the tuberculin test now. If it is positive, starting preventive therapy is extremely important and should not wait. If it is negative, it would be a good idea to repeat it after the patient responds to a HAART regimen.

Q: I have read that many patients with HIV and TB have normal chest X-rays despite having positive sputum cultures. Does this mean that I should get sputum smears and cultures on patients with a positive PPD and negative X-ray before starting prophylaxis?

A: It is certainly true that HIV-infected patients with active TB can have normal chest X-rays. As a result, there should be a low threshold for ordering sputum exams in patients with symptoms suggestive of TB. However, for a completely asymptomatic patient with a normal X-ray and a positive skin test, ordering sputum cultures is not necessary. Any pulmonary or constitutional symptoms, on the other hand, should prompt you to send off sputum studies before beginning preventive therapy.

Q: Several years ago the CDC recommended that patients on HAART be treated with a regimen that used streptomycin, and not receive rifampin or rifabutin. I don't see this in the more recent guidelines. Why not?

A: The original recommendations from the CDC suggested that a 9-month course of INH/PZA/Ethambutol/Streptomycin could be used instead of a regular, rifampin-based regimen in patients on HAART. The more recent guidelines have downplayed this for several reasons. First, this regimen is untested in patients with HIV infection, though it appears to be effective for patients without HIV. Second, it is now clear that patients can receive both effective TB treatment and HAART, without sacrificing rifamycins. Rifampin can be used with ritonavir and ritonavir combination regimens as well as efavirenz, and rifabutin can be used with most other HAART agents. Thus, there is no good reason, at least in North America, to forgo a rifamycin when treating TB. In some countries where HAART is available but rifabutin is not, the streptomycin regimen may be attractive. In my view, however, it is astonishing that governments will pay for protease inhibitors and NNRTIs but not rifabutin!

Q: Should patients on methadone not be given the 2-month rifampin/PZA regimen for latent tuberculosis infection? Should rifabutin be used instead?

A: It is certainly possible to give the short-course TB preventive regimen to patients also taking methadone, using either rifampin or rifabutin. Rifampin predictably causes methadone withdrawal because of its upregulation of P450 cytochromes, which are responsible for metabolism of methadone and other opiates. As a rule, the level of methadone will be effectively reduced by 50% within a week of starting rifampin. Thus, we routinely recommend that methadone doses be increased for patients starting rifampin. The usual schedule is to increase the dose of methadone by 5-10 mg daily until there is a 50% increase; alternatively, the dosage can be increased 20-30 mg over a week unless there are withdrawal symptoms. One problem with this is that FDA approval is required for methadone doses above 100 mg daily. Rifabutin also enhances opiate metabolism, but less dramatically and consistently than rifampin. For patients on relatively high doses of methadone, rifabutin/PZA would be a good choice, with dose adjustment based on symptoms. If this proves too tedious or challenging, the alternative of INH is still possible.

Q: Can rifampin/PZA be given twice weekly instead of daily? It is possible for our program to supervise twice weekly therapy, but not daily.

A: The recent ATS/CDC statement on treating latent TB infection lists daily rifampin/PZA as the preferred regimen, but also lists twice weekly as an alternative. Two studies examined twice weekly dosing of rifampin/PZA and found it efficacious. The ATS/CDC expert panel was somewhat antsy about this dosage, in part because the studies that used it did not compare it to 12 months of INH (both studies used 6 months of INH in the comparison arm). The evidence for efficacy is still quite impressive, however. In the one study using twice weekly rifampin/PZA where a placebo was also used, the regimen reduced TB incidence by about 77%. This level of protection is quite impressive. I would not hesitate to use the twice weekly regimen in a setting where it can be supervised and is more feasible that daily therapy.

Q: How long should a patient with a paradoxical reaction during TB therapy and HAART be treated for their TB? My patient had a worsening CXR, major lymphadenopathy and a new pleural effusion 3 months into TB treatment after starting his HAART therapy. Should I treat him only for 6 months?

A: This is a question for which there is no right answer, though most TB experts would extend treatment beyond the usual 6 months. When a patient is suspected of having a paradoxical reaction it is essential to make sure that they are not failing therapy or experiencing another opportunistic infection. If you are certain that it is a HAART-related reaction, continuing the current TB therapy is required. There are no good data for how long to continue, but you would certainly want to see the new symptoms and signs resolved for at least 3-4 months before stopping TB treatment. The situation is reminiscent of the treatment of lymphatic TB, where symptoms and signs wax and wane for months during therapy: though clinical studies suggest that treatment needn't be extended beyond 6 months, most clinicians are uncomfortable stopping treatment until 3 or more months after signs and symptoms have improved.