CDC
recomendationsIn September 1997, when CDC convened a meeting of
expert consultants to discuss current information about HIV-related TB,
special emphasis was given to issues related to coadministration of TB
therapy and antiretroviral therapy and how to translate this information
into management guidelines. Thus, these guidelines are based on the
following scientific principles:
-
Early diagnosis and effective treatment of TB among HIV-infected
patients are critical for curing TB, minimizing the negative effects of
TB on the course of HIV, and interrupting the transmission of
Mycobacterium tuberculosis to other persons in the community.
-
All HIV-infected persons at risk for infection with M. tuberculosis
must be carefully evaluated and, if indicated, administered therapy to
prevent the progression of latent infection to active TB disease and
avoid the complications associated with HIV-related TB.
-
All HIV-infected patients undergoing treatment for TB should be
evaluated for antiretroviral therapy, because most patients with
HIV-related TB are candidates for concurrent administration of
antituberculosis and antiretroviral drug therapies. However, the use of
rifampin with protease inhibitors or non-nucleoside reverse
transcriptase inhibitors is contraindicated.
General principles Ideally, the management
of TB among HIV-infected patients taking antiretroviral drugs requires
- directly observed therapy
- availability of experienced and coordinated TB/HIV care givers
- use of a TB treatment regimen that includes rifabutin instead of
rifampin in most situations
Mode of
action of antiretrovirals All these drugs act by blocking the
action of enzymes that are important for replication and functioning of
HIV. Once HIV invades a macrophage or T-lymphocyte, the enzyme HIV reverse
transcriptase initiates copying of the viral genetic code (RNA) into the
genetic code of the infected host cells (DNA). After this, HIV genetic
material is integrated into the host's DNA. This is followed by
multiplication, creating several billion new copies of HIV per day. The
enzyme protease contributes to viral reproduction by enabling the assembly
and release of viable particles of HIV from infected cells
Anti retroviral drugs:Types
Nucleoside reverse transcriptase inhibitors |
Non nucleoside reverse transcriptase inhibitors |
Protease inhibitors |
| Zidovudine(AZT,ZDV) |
Nevirapine(NVP) |
Saquinavir(SQV) |
| didanosine(ddI) |
Ritonavir(RTV) |
| Zalcitabine(ddC) |
Efavirenz(EFV) |
Indinavir(IDV) |
| Stavudine(d4T) |
Nefinavir(NFV) |
| Lamivudine(3TC) |
Delavirdine |
Amprenavir(APV) |
| Abacavir(ABC) |
Lopinavir/ritonavir) | Goals of anti retroviral therapy
- Maximal and durable suppression of viral load
- Restoration and preservation of immunologic function
- Improvenet of quality of life
- Reduction of HIV related morbidity and mortality
Tools of anti retroviral therapy
- Maximize adherence to the antiretroviral regimen
- Rational sequencing of drugs
- Presevation of future treatment options
- Use of resistance testing in selected settings
Interactions between antiretrovirals and rifampicin
The Rifamycin antibiotics (Rifampin & Rifabutin) stimulate the
activity of the enzyme system in the liver (cytochrome P450) that
metabolises Protease Inhibitors (PIs) and Non Nucleoside Reverse
Transcriptase Inhibitors (NNRTIs). This can lead to a reduction in the
blood levels of the PIs and the NNRTIs. Conversely, PIs and NNRTIs may
also enhance or inhibit this same enzyme system, although to individually
different extents, and can lead to altered blood levels of the Rifamycin
antibiotics. The potential drug to drug interactions may result in
ineffectiveness of the antiretroviral drugs, to ineffective treatment of
tuberculosis or to an increased risk of drug toxicity.It is worth noting
that:
- Rifabutin, can be used with all PIs (except
Saquinavir) and with all NNRTIs
- Delavirdine), although dosage adjustments are sometimes
necessary.
- Isoniazid, which is recommended for the preventive therapy of
tuberculosis, is free from any interactive effect with PIs and NNRTIs.
- The Nucleoside Reverse Transcriptase Inhibitors (NRTIs) are not
metabolised by the cytochrome P450 enzyme system and are free from
interaction with either of the Rifamycin antibiotics.
Treatment of TB and HIV in resource poor
countries It has been suggested that in resource limited settings,
patients with active tuberculosis should not commence ART until
chemotherapy for tuberculosis has been completed. While this would greatly
simplify treatment regimens and enhance adherence, the effects of this
approach on the overall outcomes of treatment have not been fully
evaluated and further research is needed.
In general, the treatment of tuberculsosis should be in accordance with
the recommendations of the National Tuberculosis Programme in each
country. |
