Starting Treatment For Either Hiv Or Tb
The decision to start treatment for either HIV or TB when there is co-infection, should take into account a number of factors including:
- Has the person got symptoms of, and is ill with either TB, or some other HIV related opportunistic infection?
- Is the person already having treatment for either TB or HIV infection?
- What drugs are available for the treatment of HIV infection, and indeed TB, if the person is not already receiving treatment?
- If there is a need for both HIV and TB treatment, are there experienced health care workers and/or guidelines available to provide the necessary expertise on this?
Timing Of Art Initiation
Antiretroviral medication should be initiated in all PLHIVs, especially those with TB coinfection. WHO recommends to start ART, regardless of CD4 T lymphocyte count, within two weeks of initiating ATT . In persons with CD4 T lymphocyte count â¤50 cells/mm3, a meta-analysis found that starting ART sooner reduced death at one year. There was no evidence that early ART was beneficial or harmful in persons with higher CD4 T lymphocyte counts .
Table 1 Summary of the treatment for TB and HIV based on WHO guidelines .
Diagnosing Tb And Hiv When There Is Co
Because of the limitations of current TB tests, it is even more difficult to diagnose TB in HIV positive individuals, than to diagnose TB in people without HIV infection. Many people with HIV will have a false negative result from a TB sputum smear test. This can result in a large number of cases of active TB disease going undiagnosed.
Globally in 2018, 64% of notified TB patients had a documented HIV test. This was an increase from 60% in 2017. In the WHO African region, where the burden of HIV associated TB is highest, 87% of TB patients had a documented HIV test result.
A total of 477,461 TB cases among HIV positive people were reported . Of these 86% were on antiretroviral therapy.
According to the World Health Organisation improvements are still needed globally in the detection of active TB disease among PLHIV, the coverage of HIV testing among TB patients, and the enrolment of HIV positive TB patients in ART.
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Treatment Of Tb In Hiv
The principles for treatment of active TB disease in HIV-infected patients are the same as those for HIV-uninfected patients. TB treatment is the priority. The regimens should include rifampicin and isoniazid . The 6-month duration with standard regimen among HIV-infected patients showed similar cure and treatment failure rates as in HIV-uninfected patients . However, a meta-analysis on treatment of active TB in HIV-infected patients suggested that longer duration of rifamycin therapy were associated with a lower risk of TB relapse . Intermittent intensive-phase treatment was associated with increased odds of treatment failure . ART was found to lower the risk of TB relapse . Studies to assess duration of rifamycin-based TB treatment and dosing schedule in patients receiving ART are needed for further evaluation. Currently, the World Health Organizations guideline for the treatment of TB recommends that HIV-infected patients should, as a minimum, receive the same duration and daily dosing of TB treatment as HIV-uninfected patients. ART should be initiated in all HIV-infected with TB patients, irrespective of CD4 cell count .
Starting Both Hiv Arv And Anti Tb Drug Therapy
For adults with co-infection, who need to receive both antiretrovirals and TB drugs, the WHO guidelines recommend starting ARVs within the first 8 weeks of starting TB treatment. This should be two weeks in individuals who have a CD4 count of less than 50. It is not now considered necessary to delay the initiation of ARV therapy until TB treatment has been completed.8
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Rapid Progression And Higher Mortality
TB tends to progress more rapidly in HIV-1 infected persons and may present as an acute illness , . Amongst South-African gold miners who were diagnosed with TB the mean duration of smear positivity before diagnosis was substantially shorter for HIV-1-infected compared to uninfected TB patients . This indicates more rapid progression of disease and subsequent diagnosis of TB in HIV-1 infected patients compared to TB patients who were not HIV-1 infected. Similar findings were noted in a community-based study in Zimbabwe: duration of infectiousness prior to TB diagnosis was 18 weeks for HIV-1 infected versus 1 yr for HIV-1 uninfected patients . TB may also present as an acute community acquired pneumonia and needs to be considered in any HIV-1 infected patient presenting with acute respiratory illness , .
Diagnosis Of Tb In Hiv
A definitive diagnosis of TB is confirmed by culturing M. tuberculosis organisms from a specimen obtained from the patient. For pulmonary TB, sputum-smear for Ziehl-Neelsen staining is fast, inexpensive, and a highly specific method. However, the sensitivity of direct microscopy in searching for acid-fast bacilli is variable from 31 to 80 % according to a previous review . Studies from Africa found that patients with concurrent HIV and TB infection have a higher frequency of smear-negative TB than those of HIV-uninfected patients . Concentrating the specimen provided an additional positive yield of 36 % for the sputum-negative patients in a high HIV-prevalent area . Currently, sputum microscopy and culture in liquid medium with subsequent drug-susceptibility testing are recommended as standard method for diagnosing active TB . Nevertheless, the use of solid culture medium may be more cost-effective in resource-limited countries. In systematic review, the mean time to detection with Löwenstein-Jensen cultures was 24 days, whereas automated mycobacterial liquid culture systems had a mean time to detection of 15 days . Drug resistant TB substantially reduces survival in HIV-infected patients with TB . Early detection and optimal treatment of drug resistant TB are crucial. Susceptibility testing of M. tuberculosis should be performed wherever this test is available.
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Tb Diagnosis And Treatment
In the early empirical group , TB treatment was initiated within 6 hours for 35 patients, and within 24 hours in 73 patients. Median time to TB treatment was 15 hours . In comparison, only 50 of 240 patients in the STAMP trial received TB treatment within 24 hours of admission, and median time to TB treatment was 24 hours .
The basis for starting early empirical TB treatment was results of radiology in 50 patients , other investigations in 22 , and clinical features alone in 28 . In total, 72 of 100 patients had a chest radiograph interpreted by clinicians as consistent with TB, of whom 42 were started on TB treatment based on this interpretation. Abnormal CSF protein and/or cell counts were the reason for starting TB treatment in 19.0% of patients. Twenty-four percent were treated for pulmonary TB and 25.0% for TB meningitis, and the remaining 51% were treated for extrapulmonary or disseminated TB . The decision to start TB treatment was made by senior clinicians for 66% of patients. Among patients screened for TB in the STAMP trial, TB treatment based only on clinical features or CSF was uncommon .
Screening For Ltbi In Persons With Hiv
The WHO and the US DHHS recommend screening all PWH for LTBI at the time of HIV diagnosis, regardless of their epidemiologic risk factors or TB exposure history . In addition to symptom screening, the two currently available methods for the diagnosis of LTBI are the tuberculin skin test and the interferon gamma release assay . IGRA testing is expensive and not widely available in low- and middle-income countries, and reagents for TST are often in short supply therefore, the WHO guidelines do not require LTBI testing before initiating TPT for PWH . Moreover, PWH have been shown to benefit from TPT even with negative LTBI testing .
All individuals with HIV who have a new positive test for LTBI should be offered LTBI treatment after active TB disease is ruled out . Additionally, the US DHHS recommends treatment of LTBI for PWH who report close contact with anyone with infectious TB, regardless of their TB screening test results . PWH in the USA who have negative screening tests for LTBI and no recent contact with anyone with infectious TB are unlikely to benefit from treatment of LTBI .
While both the TST and IGRA help differentiate those with LTBI from those without LTBI, the diagnostic accuracy of both tests is limited. It is important to note that these tests do not distinguish between LTBI and active disease. Additionally, negative LTBI testing does not definitively rule out underlying disease.
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Pi And Rifamycins: What To Do
PI/ritonavir combinations tend not be given with rifampicin, thus, either the ART regimen should be modified to one containing efavirenz if possible or rifabutin should be used instead of rifampicin. In resource-limited settings where rifabutin is not available additional ritonavir boosting of lopinavir has been used with rifampicin. This is done by either adding high-dose ritonavir to lopinavir/ritonavir combination or by doubling the lopinavir/ritonavir dose to overcome the induction by rifampicin. In healthy volunteer and patient studies, high rates of hepatic events and gastro-intestinal intolerance have been reported with such strategies and patients should be carefully monitored for the development of jaundice or hepatitis , . Quadruple nucleosides are also a possibility as ART. The choice of any ART regimen depends on baseline and subsequent resistance testing and history of drug exposure if there has been virological failure.
Considerations When Tb Is Diagnosed In People Living With Hiv Who Are Already Receiving Antiretroviral Therapy
When TB is diagnosed in patients already receiving ART, TB treatment should be started immediately. There are two issues to consider in such cases: whether ART needs to be modified because of drugdrug interactions or to reduce the potential for overlapping toxicities, and whether the presentation of active TB in a patient on ART constitutes ART failure that requires a change in the ART regimen. Diagnosis and management of ART failure are covered in another WHO document .
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Antiretroviral Therapy For Patients With Hiv And Active Tuberculosis
All patients with HIV/TB disease should be treated with ART , although the timing of ART initiation may vary as discussed below. Important considerations related to the use of ART in patients with active TB disease include the following:
- When to start ART in the setting of drug-resistant TB and in patients with TB meningitis,
- Significant PK drug-drug interactions between anti-TB and ARV agents, and
- The development of TB-associated immune reconstitution inflammatory syndrome after ART initiation.
Active pulmonary or extrapulmonary TB disease requires prompt initiation of TB treatment. The treatment of active TB disease in patients with HIV should follow the general principles guiding treatment for patients without HIV. The Adult and Adolescent Opportunistic Infection Guidelines include a more complete discussion of the diagnosis and treatment of TB disease in patients with HIV. In general, standard anti-TB therapy should be used for patients with HIV and drug-susceptible TB, consisting of 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol , followed by 4 months of isoniazid and rifampin .
Tuberculosis Diagnosed While a Patient is Receiving Antiretroviral Therapy
ART should be continued when TB is diagnosed in a patient receiving ART, but the ARV regimen should be assessed with particular attention to potential drug interactions between ARVs and TB drugs . The patient’s ARV regimen may need to be modified to permit use of the optimal TB treatment regimen .
Diagnosis Of Active Tb
In the absence of a positive smear the chest radiograph may play an important role in the diagnosis of HIV-1 patients with suspected TB. There are several chest radiograph features that are highly suggestive of TB, but none are diagnostic , , . The degree of immunosuppression plays a critical role in the radiographic pattern , . Persons with relatively well-preserved immunity can present with a typical adult pattern with upper lobe predominance and cavitation. In patients with more advanced immunosuppression the radiological features tend to be more atypical with mid- or lower-zone infiltrates and hilar and mediastinal lymphadenopathy , , , , . Pleural effusions can occur irrespective of immune status . A miliary pattern occurs commonly with more advanced immunosuppression . It is also well described that HIV-1 infected patients with active TB proven on sputum culture can have normal chest radiographs , , .
In the absence of any microbiological evidence of TB, guidelines for diagnosis exist . Expanded case definitions have performed well but should be combined with follow-up and objective assessment of response to treatment . HIV-1 infected patients with smear-negative TB have a higher mortality than smear positive patients , , , . Therefore, it is important that patients who fail to respond to treatment for smear-negative TB should be referred for further investigation as they may have drug-resistant disease or an alternative diagnosis .
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Adverse Reactions And Tuberculosis Immune Reconstitution Inflammatory Syndrome
Medication-induced liver injury has been linked to all antiretroviral drug classes and some anti-TB treatments such as pyrazinamide, isoniazid, and rifampicin . When efavirenz and nevirapine were given together with TB treatment, there was an increase in hepatotoxicity . Alcoholism, co-infection with Hepatitis B and C, IRIS hepatitis, and obstruction by nodes at the porta hepatitis all lead to liver injury, as do shared metabolic pathways of anti-TB and antiretroviral medicines. Other side effects include cutaneous and gastrointestinal problems, as well as peripheral neuropathy, which can be severe at times . These side effects include drug rashes , gastro-intestinal intolerance , and neuropsychiatric side effects . Several factors found to be associated with poor treatment outcomes – smoking, history of hospitalization upon starting treatment, lower TB symptom score, internalized stigma , male patients and those with alcoholism , older age, HIV co-infection and rural residence , diabetes mellitus should be addressed appropriately for better TB cure.
How Common Is Hiv/tb Coinfection
Worldwide, TB disease is one of the leading causes of death among people with HIV. In the United States, where HIV medicines are widely used, fewer people with HIV have TB disease than in the past. But TB disease still affects many people with HIV in the United States, especially those born outside the United States.
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What Is The Treatment For Tb
TB medicines are used to prevent latent TB infection from advancing to TB disease and to treat TB disease. The choice of TB medicines and the length of treatment depend on whether a person has latent TB infection or TB disease.
People with HIV/TB coinfection should be treated for both HIV and TB however, when to start treatment and what medicines to take depends on a persons individual circumstances. Taking certain HIV and TB medicines at the same time can increase the risk of drug-drug interactions and side effects. People being treated for HIV/TB coinfection are carefully monitored by their health care providers.
If you have HIV/TB coinfection, talk to your health care provider about a treatment plan that works for you.
Integrated Therapy Of Hiv And Tb: General Concept
Integrated therapy is crucial for HIV-infected patients with TB. The two diseases, HIV and TB, must be managed simultaneously. TB-related mortality in HIV-infected patients is high during the first few months of TB treatment . Additionally, evidence from randomized clinical trials and systemic review has shown that early initiation of ART improves survival of HIV-infected patients with TB . Managing the two diseases more effectively during this critical period is therefore essential to improve the patients survival and quality of life. The World Health Organization guidelines have recommended ART initiation during this time period . However, ART initiation is often delayed due to various factors such as patient characteristics, overlapping drug toxicities, fear of clinicians or patients, and policies of local HIV and TB programs. Delay in initiating ART is more common among patients referred from TB to HIV separate clinics . Delays in the initiation of ART in HIV-infected patients with TB, particularly those with very low CD4 cell counts, are associated with increased mortality risk.
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Mdh Tb Medications Program
Any person in Minnesota receiving treatment for LTBI or active TB disease is eligible to receive TB medications at no cost to the patient from the MDH TB Prevention and Control Program. Treatment regimens must follow Centers for Disease Control and Prevention/American Thoracic Society/ Infectious Diseases Society of America treatment guidelines.
- To request medications, the prescribing clinician should contact MDH at 651-201-5414 or 1-877-676-5414 . You will be asked to provide pertinent demographic and clinical information and a copy of the prescription.
- Through a contracted pharmacy, MDH sends a monthly supply of patient-specific TB medications to the designated clinic, local public health agency, or other health care provider licensed to administer medications.
- The health care provider who receives the medications is responsible for monitoring the patient for adherence, adverse reactions, and signs of active TB disease that may develop during treatment. A monitoring flow sheet for LTBI treatment is available at Tuberculosis Medications Program.
Hiv Makes Tb More Difficult To Diagnose And Treat
The sputum of an HIV-positive person usually contains a lower concentration of TB bacteria, making it harder to detect in a sputum test. Extra-pulmonary TB, which is more common among HIV-positive people than HIV-negative people, cannot be detected through either sputum smear microscopy or chest x-rays.
TB medication and antiretroviral therapy need to be carefully monitored to avoid adverse drug interactions and side effects in patients. Treatment may take longer in people living with HIV, due to the likelihood of extra-pulmonary TB. Even after treatment, they are more vulnerable to getting TB again. Those who have been treated for pulmonary TB remain infectious to others for longer after initiating treatment.
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