Posting #8 - Relevant Links

A few of the links that were essential to research on this topic!

The World Health Organization has two webpages that give a global perspective on the HIV/TB co-infection epidemic:

This site gives basic information, current updates and links to other relevant sites:
WHO - Tuberculosis and HIV

This is the entry into the WHOSIS database, where country, regional, or global data on
HIV/TB statistics can be obtained:
WHOSIS

WHO works in conjunction with UNAIDS on many HIV/TB programs:
UNAIDS

The Center for Disease Control and Prevention has US relevant information
CDC - Tuberculosis and HIV

Stop TB Partnership is a network of international organizations, countries, donors from the public and private sectors, governmental and nongovernmental organizations and individuals and has a very comprehensive global partner network.

Several good non-governmental agencies also provide web-based information for TB/HIV:
AVERT is a UK-based international organization dedicated to stopping the spread of AIDS
Internation Union Against Tuberculosis and Lung Disease works on issues of TB globally
for low and middle income populations
LEPRA society works on several endemic diseases in India including TB and HIV
AIDS Foundation East-West works with international and local partners in Eastern Europe
and Central Asia on HIV related issues

Knowledgebase and publication sites include:
UCSF HIV Insite provides up to date information and article links for HIV related news
HIV Policy.org provides information on a variety of health publications for Asia
International Journal of Infectious Disease publishes articles related to Infectious Disease,
believe it or not!

In addition, the following websites have treatment and diagnosis guidelines for HIV/TB:
UpToDate is a comprehensive guidelines subscription database based out of the
University of Washington

Posting #7 - Effect of HIV on Diagnosis of TB disease

Diagnosis of TB in HIV+ Patients
Effect of HIV on TB

The main effect of HIV on TB

• Cell-mediated immunity is the host's main defense against TB
• CD4+ cells are a key part of cell-mediated immunity
• CD4+ are depleted by HIV infection
• HIV reduces the host's ability to fight off primary infection

Key question

• What is the Patient's CD4 cell count?

CD4 cell count > 200 cells/μL

Clinical presentation is similar to HIV seronegative patients

• Primarily pulmonary TB
• Nights sweats
• Fever
• Weight loss
• Fatigue/malaise
• Cough w/sputum

Diagnostics are similar to HIV seronegative patients

• PPD > 5mm induration is positive
• Acid-fast staining: AFB has high sensitivity, low specificity (high false negatives)
• Chest X-rays: pulmonary cavitation in upper lung fields
• Sputum culture is still gold standard

CD4 cell count

• Unexplained fevers
• Lymphadenopathy, especially in extrathoracic nodes (cervical & axillary)
• Some will still present as typical seronegative patient

Diagnostics are similar to primary infection

• PPD: high false negatives d/t anergy
• QFT-G: high number of indeterminate results
• Acid-fast staining: often negative
• Sputum culture: Still the best test, highest sensitivity and specificity. Be sure to do the 3 separate sputum sample. Repeat test if TB is still suspected!

Chest Radiographs

• may be normal
• may have non-cavitatory infiltrates in middle or lower lung fields, intrathoracic lymphadenopathy consistent with primary TB
• may be typical of TB disease in seronegative patients

Clinical presentation is more likely to be a disseminated/extrapulmonary tuberculosis

• TB can present anywhere, although lymph nodes and pleural space is most likely
• Test serum and urine cultures - good test for disseminated TB
• Abdominal/Pericardial TB
• Lymph node aspiration – swelling of nodes
• Head CT/Lumbar puncture for CSF - meningitis
• Sample sites if relevant to S/Sx

Summary

• TB can be sub-clinical
• Manifested as indeterminate symptoms
• Has higher mortality
• More difficult to diagnose in TB endemic areas
• Complicated by limited resources
• Low cost effective diagnostic tool is still needed
• High cost effective diagnostic tool isn't available yet.

References

American Thoracic Society. (2000). Diagnostic Standards and Classification of Tuberculosis in Adults and Children. American Journal of Respiratory and Critical Care Medicine, 161, 1376–1395.

El-Sadr, W. M., & Tsiouris, S. J. (2008). HIV-associated tuberculosis: diagnostic and treatment challenges. Seminars in Respiratory and Critical Care Medicine, 29(5), 525-531. doi: 10.1055/s-0028-1085703

Maartens, G. (2009). Clinical features and diagnosis of tuberculosis in HIV-infected patients. Retrieved November 24, 2009, from http://www.uptodate.com.offcampus.lib.washington.edu/online/content/topic.do?topicKey=tubercul/7537&selectedTitle=1%7E150&source=search_result

Post, F. A., Wood, R., & Pillay, G. P. (1995). Pulmonary tuberculosis in HIV infection: radiographic appearance is related to CD4+ T-lymphocyte count. Tubercle and Lung Disease: The Official Journal of the International Union Against Tuberculosis and Lung Disease, 76(6), 518-521.

Posting #6 - Adherence and DOT for patients with a co-infection of HIV and TB

The standard of care for tuberculosis (TB) in recent years has been Direct Observed Therapy (DOT), which is defined as a health care worker or designated person directly observing the administration and ingestion of medication. In regards to HIV seropositive patients, the Center for Disease Control (CDC) recommends DOT for TB medications (Center for Disease Control [CDC], 1998; Kaplan, et al., 2009). In addition, the CDC recognizes the importance of providing social and medical support to enhance adherence to a medication regime.

Many obstacles to successful treatment lie in the path of patients with TB. Among those are long course of therapy, side effects of medications, multiple drugs taken multiple times of day, difficulty in making appointments due to issues of transportation and money, cultural insensitivity of clinic workers, stigma, lack of support by community, mental health, drug and ETOH abuse, and previous failed treatment (Lee B Reichman, MD & Alfred A Lardizabal, MD, 2009). It is quite an impressive list. If the patient has a co-infection of HIV, these obstacles are compounded by even more medications, an increasingly complex schedule of treatment, more clinic appointments, providers who may be inexperienced in dealing with co-infections of TB and HIV, added medication side effects and interactions, and the prospect of taking medications for a lifetime. This can be a daunting task, even for people with great organizing and coping skills. For someone who may be homeless, just barely holding onto a job and trying to survive day-to-day, this scenario can be overwhelming. Even health care providers can fall into the non-adherence category (Miller & Snider, 1987).

Fortunately, providing good support in addition to DOT can make a difference in helping patients negotiate difficulties in treatment of a co-infection of HIV and TB. Treat patients with respect during all interactions, whether in the hospital, clinic, or at a home visit. Education of the patient about the basics of why adherence is important, that TB can be cured and they can live a long life even with HIV. They should also be made aware of the side effects of their medications, what to do if they experience the side effects, and that they should contact their provider before discontinuing their medications, if the side effects are severe enough that they don't want to continue taking their medications. Non-judgmental questioning of the patient's medication adherence, while at the same time being able to explain the consequences of non-adherence including being sick longer, the probability of relapse and a more complicated drug regimen. Medical support can include helping the patient find better timing for medications, switching to combination drugs, adjusting dosages, or even reducing weekly frequencies of medication. Under DOT, dosage frequency can be reduced to 3 times weekly for TB medications. Provider appointments, excluding DOT, should be every week to two weeks initially until the patient stabilizes on their medications and they have had a chance to get answers for all their TB and HIV related questions, then the appointments can be every three months. Help patients find ways to remember taking medications including cell phone reminders, calendars, associate with other daily tasks such as tooth brushing. Phone call reminders and incentives such as bus tickets and food vouchers that are offered by the health department may also help encourage adherence to their DOT and clinic appointments.

The future of treatment for co-infection of HIV and TB may rely on the ability to pool the resources for treatment of both diseases, especially in resource poor settings. Providers and researchers are starting to look at ways to alleviate the obstacles patients face in the dual treatment regimens. Combining DOT and support services for HIV and TB during the course of TB treatment has shown promise. Two studies in resource poor settings, one in Peru and another in South Africa, combined resources for both HIV and TB treatment (Jack et al., 2004; Muñoz et al., 2009). Both studies saw a high cure rate of TB, increase of average CD4 count, reduction in average HIV viral load. The Jack study saw only a minimal increase in costs over DOT implementation for TB alone. The Muñoz study was a case-control study that also looked at psychosocial outcomes. It found that the participants indicated a greater quality of life, better communication with their providers, and more motivation to adhere to their medication regimen.

References

Kaplan, J. E., Benson, C., Holmes, K. H., et al. (2009). Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recommendations Rep 2009, 58, 1-198.

Center for Disease Control. (1998). Prevention and treatment of tuberculosis among patients infected with human immunodeficiency virus: Principles of therapy and revised recommendations. Centers for Disease Control and Prevention. MMWR Recommendations Rep 1998, 47, 1-51.

Jack, C., Lalloo, U., Karim, Q. A., Karim, S. A., El-Sadr, W., Cassol, S., et al. (2004). A pilot study of once-daily antiretroviral therapy integrated with tuberculosis directly observed therapy in a resource-limited setting. Journal of Acquired Immune Deficiency Syndromes (1999), 36(4), 929-934.

Lee B Reichman, MD, & Alfred A Lardizabal, MD. (2009, September). Adherence to tuberculosis treatment - UpToDate. Retrieved November 24, 2009, from http://www.uptodate.com.offcampus.lib.washington.edu/online/content/topic.do?topicKey=tubercul/6460&selectedTitle=1%7E150&source=search_result

Miller, B., & Snider, D. E. (1987). Physician noncompliance with tuberculosis preventive measures. The American Review of Respiratory Disease, 135(1), 1-2.

Muñoz, M., Finnegan, K., Zeladita, J., Caldas, A., Sanchez, E., Callacna, M., et al. (2009). Community-based DOT-HAART Accompaniment in an Urban Resource-Poor Setting. AIDS and Behavior. doi: 10.1007/s10461-009-9559-5

Posting #5 - Immune Reconstitution Inflammatory Syndrome

What is IRIS?

Immune reconstitution inflammatory syndrome (IRIS) is the dysfunctional operation of the immune system when ART treatment for an HIV infection allows the immune system to become effective again. In essence, the immune system is acting as if an infection is still present and reacts to it, causing the inflammatory manifestations typical of the original disease. Paradoxical IRIS occurs when the reaction is to a previously known infection in the person, while unmasking IRIS is when the reactions is to an infection that wasn't previously diagnosed in the person (Kelley & Armstrong, 2009).

Who does it affect?

People who are just starting their ART therapy for the first time or who are restarting their therapy after being off the therapy for while. Diseases and infections most associated with IRIS are tuberculosis, herpes simplex, herpes zoster, Hepatitis B & C, Karposi sarcoma, Cryptococcal neoformans, and mycobacterium avium complex.

What are the risk factors?

Low CD4+ count at the start of ART therapy, usually less than 100cells/mm3, was found in multiple studies. Recent research indicates the possibility that starting ART soon after an opportunistic infection has been found, the serum antigen from that infection will be elevated, and stimulate IRIS.

How is IRIS diagnosed?

No diagnostic marker exists, so no definitive lab test can identify the syndrome. Diagnosis is complicated by the fact that the immune system's reaction to the absent infection (IRIS) is identical to its reaction to an infection that actually exists. This is particularly difficult with unmasking IRIS, since the disease wasn't previously diagnosed in the individual, and it is unknown whether the signs and symptoms are related to a new infection or unmasking IRIS. Care must be taken to confirm that the symptoms do not represent an actual new or recurring infection, or are not result of a drug interaction.

What is the treatment?

Generally, the inflammatory process dies down after an average of about 2 months, requiring only supportive care. Occasionally, hospitalization and corticosteroid treatment are necessary.

What is IRIS in relation to tuberculosis?

In 2006, over 100 researchers gathered to define three different syndromes or conditions with similar symptomology: paradoxical TB-IRIS and unmasking TB-IRIS, both noted above, and ART-associated TB. The main difference in relating IRIS to TB is that if the patient was not diagnosed with TB prior to initiation to ART, and the disease is "unmasked" by ART, the immune system will most likely not have resolved the TB infection. Thus, it is likely that true unmasking TB-IRIS is rare, and instead the patient has active TB! For this reason, the consensus of the researchers was that patients who present with symptoms of previously undiagnosed active TB while on ART be diagnosed with ART-associated TB. A sub-category of unmasking TB-IRIS was defined as well. A rough outline of the definitions is listed below (Meintjes et al., 2008):

• For paradoxical TB-IRIS, since TB would have been already diagnosed, the patient will have at least started TB therapy and most likely be on that therapy at the time of initiation of ART therapy (the latter is not a requirement of diagnosis). The patient would also need to have responded to TB therapy and be free of symptoms of active TB at the time of initiation of ART therapy. In addition, clinical symptoms of TB must be present as well, such as fever, lymphadenopathy, cough, or evidence of additional pulmonary infiltrates (if the patient had pulmonary TB). Other clinical diagnoses must be ruled out, such as TB drug resistance, drug interactions or other opportunistic infections.

• For ART-associated TB, TB treatment would not have been started by the time of ART initiation, and active TB is diagnosed subsequently by means of WHO criteria.

• For unmasking TB-IRIS, the same criteria as for ART-associated TB plus either: a disproportionate response of the immune system to active TB particularly in regards to inflammatory presentation or a paradoxical reaction after a patient has been established on the TB treatment.

References

Kelley, C. F., & Armstrong, W. S. (2009). Update on immune reconstitution inflammatory syndrome: progress and unanswered questions. Current Infectious Disease Reports, 11(6), 486-493.

Meintjes, G., Lawn, S. D., Scano, F., Maartens, G., French, M. A., Worodria, W., et al. (2008). Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. The Lancet Infectious Diseases, 8(8), 516-523. doi: 10.1016/S1473-3099(08)70184-1

Posting #4 - Gold standard in LTBI testing for TB in people who are HIV+?

The tuberculin skin test (TST) has been used historically to test individuals for latent TB infection (LTBI) and has a sensitivity and specificity of approximately 90% in immunocompetent people. Since the discovery of Human Immunodeficiency Virus (HIV), the global TB picture has changed considerably, including the way we test for LTBI. In the context of an HIV infection, the TST has proven to have a much lower sensitivity and specificity than with immunocompetent people. The reduced reliability of the TST in HIV patients has led to a search for a test that will perform better with those patients. Interferon-γ release assays (IGRA), including QuantiFERON-TB Gold (QFT-G) have been studied as a possible replacement for the TST due to the limitations of the TST in testing the general population, particularly in areas where the bacillus Calmette-Guerin (BCG) vaccine is being used. QFT-G testing in the general population has compared favorably to TST (Fietta, et al., 2003; Detjen, et al., 2007), so studies were undertaken to determine if QFT-G would overcome the reliability problems of the TST in HIV positive patients.

The question of reliability for testing of LTBI has to include the discussion of what is considered reliable. When talking about reliability, many times it isn't reliability that is being discussed, but validity. Reliability, strictly speaking, means that a test gets the same result every time, while validity means that the test is accurate. In this case, it is the relative validity, or accuracy, of the tests that is in question. Usually, a test for a particular condition is found that has a relatively high sensitivity and specificity. That test is then considered to be the gold standard for that particular condition. Other tests can be compared to the gold standard to determine their relative accuracy (Michel, Mouillet, and Salmi, 2006). Unfortunately, in the case of LTBI, there is no gold standard. Since there is no way to confirm the presence of TB until it progresses into a clinical illness, there isn't any way to determine the accuracy of LTBI tests. This is particularly true of LTBI in HIV positive patients where anergy reduces the response of the immune system to the TST. So the challenge in this case is to determine the accuracy of both tests without knowing the true status of the LTBI patients who are being tested. To try to resolve this issue, two different strategies were employed. One was to try both tests on patients were had confirmed TB disease and find how many tested positive. This would give us the sensitivity for both tests. The other strategy was to test people who had known risk factors, compare the results of both tests with each other and against a predicted value of positive results. One other factor was important to take into consideration in regards to test strategies. The efficacy of testing is related to the prevalence of the infection in the population being tested. If TB is not endemic in the population, the positive predictive value of the test (the chance that you actually have the condition if you test positive) will be low, even if the sensitivity and specificity are high. This effects the cost effectiveness of the test.

Four studies were selected to compare the sensitivity of QFT-G versus TST in people with active tuberculosis (Raby et al., 2008; Vincenti et al., 2007; Syed Ahamed Kabeer et al, 2009; Rangaka et al., 2007). Three studies were found that compared the results of QFT-G with TST where subjects did not active cases of TB, but had risk factors associated with TB infection (Luetkemeyer et al., 2007; Raby et al., 2008; Jones et al., 2007).

The results from the studies were mixed overall. In those among high prevalence groups, either all with active TB or in high LTBI settings, two studies showed that QFT-G was significantly more sensitive and two showed no significant difference. More information as to the methodology of the studies would be necessary to determine the validity of each of these studies, but on face value, there is some evidence that QFT-G is more sensitive in high prevalence settings. For the studies in low prevalence settings, the results uniformly showed that there was no significance between the two tests. No studies were found that compared the specificity of the two tests.

A couple of statistics from the studies did stand out. Both tests generally performed poorly in testing for TB in HIV negative subjects. In only two studies out of four, results between HIV positive and HIV negative subjects was equivalent (QFT-G in Jones et al., 2007; Rangaka et al., 2007) and in one study, both of those results were significantly less than was reported for the TST results for HIV negative subjects. Also, as the CD4 count dropped below 100, the QFT-G indeterminate results increased significantly. The significance of this result is that QFT-G indeterminate results correlate to an anergy response while the TST doesn't distinguish between a negative and an anergy response. This may be helpful in determining true negative results, although further research needs to be done in this area.

Finally, a gold standard has yet to be established. Neither the QFT-G or TST can be considered a gold standard, especially in regards to testing of LTBI in HIV positive people. Valid reasons exist to use the QFT-G instead of a TST, though. Concerns about a patient not showing up for a 2nd visit to get a reading of their TST result or testing in areas where the BCG vaccine is widely used are among those reasons. The wide variation in data shows that further work needs to be done to determine the factors in HIV positive patients that hamper validity in TB testing.

Reference

Detjen, A. K., Keil, T., Roll, S., Hauer, B., Mauch, H., Wahn, U., et al. (2007). Interferon-gamma release assays improve the diagnosis of tuberculosis and nontuberculous mycobacterial disease in children in a country with a low incidence of tuberculosis. Clinical Infectious Disease, 45, 322.

Fietta, A., Meloni, F., Cascina, A., Morosini, M., Marena, C., Troupioti, P., et al. (2003). Comparison of a whole-blood interferon-gamma assay and tuberculin skin testing in patients with active tuberculosis and individuals at high or low risk of Mycobacterium tuberculosis infection. American Journal of Infectious Control, 31, 347-53.

Jones, S., de Gijsel, D., Wallach, F.R,, Gurtman, A.C., Shi, Q., Sacks, H. (2007). Utility of QuantiFERON-TB Gold in-tube testing for latent TB infection in HIV-infected individuals. International Journal of Tuberculosis Lung Disease, 11, 1190-5.

Luetkemeyer, A.F., Charlebois, E. D., Flores, L. L., Bangsberg, D. R., Deeks, S. G., Martin, J.N., et al. (2007). Comparison of an interferon-gamma release assay with tuberculin skin testing in HIV-infected individuals. American Journal of Respiratory Critical Care Medicine, 175, 737-42.

Michel, P., Mouillet, E., Salmi, L. R., (2006). Comparison of Medical Subject Headings and standard terminology regarding performance of diagnostic tests. Journal of the Medical Library Association, 94, 221-223.

Raby, E., Moyo, M., Devendra, A., Banda, J., De Hass, P. Ayles, H., et al. (2008). The effects of HIV on the sensitivity of a whole blood IFN-gamma release assay in Zambian adults with active tuberculosis. PLoS One, 3, e2489.

Rangaka, M. X., Diwakar, L., Seldon, R., van Cutsem, G., Meintjes, G. A., Morroni C, et al. (2007). Clinical, immunological, and epidemiological importance of antituberculosis T cell responses in HIV-infected Africans. Clinical Infectious Disease, 44, 1639-46.

Rangaka, M. X., Wilkinson, K. A., Seldon, R., Van Cutsem, G., Meintjes, G. A., Morroni, C., et al. (2007). Effect of HIV-1 Infection on T-Cell–based and Skin Test Detection of Tuberculosis Infection. American Journal of Respiratory Critical Care Medicine, 175, 514-520.

Syed Ahamed Kabeer, B., Sikhamani, R., Swaminathan, S., Perumal, V., Paramasivam, P., Raja, A. (2009). Role of interferon gamma release assay in active TB diagnosis among HIV infected individuals. PLoS One, 4 , e5718.

Vincenti, D., Carrara, S., Butera, O., Bizzoni, F., Casetti, R., Girardi, E., et al. (2007). Response to region of difference 1 (RD1) epitopes in human immunodeficiency virus (HIV)-infected individuals enrolled with suspected active tuberculosis: a pilot study. Clinical Experimental Immunology, 150, 91-8.

Posting #3 - Treatment of Tuberculosis in Patients who are HIV positive: The Basics

Posting #3

Treatment of Tuberculosis in Patients who are HIV positive: The Basics

Treatment of patient co-infected with HIV

• Efficacy of both HIV and TB treatment have been shown to be effective for people with an HIV/TB co-infection.

• Drug interactions between the two therapies, adverse reaction of a patient to any of the medications, patient compliance, and drug resistance are the main concerns in prescribing therapies for a co-infection.

• Currently, it is recommended that both therapies are started at the same time.

Recommended initial TB drugs for HIV seropositive or seronegative patients

• Isoniazid (INH) - 300mg PO Qday, Rifamycin (RIF) - 600mg Qday, Pyrazinamide (PZA) - 1500mg PO Qday, Ethambutol (EMB) - 1200mg PO Qday for 7 days/wk for 8 weeks or 5 days/wk for 8 weeks if on DOT

• then INH and RIF for 7day/wk for 18 weeks or 5 days/wk for 18 weeks if on DOT

• Vitamin B-6 (pyridoxine) supplementation should be taken by any patients taking INH and efavirenz

Recommended initial HIV drugs for co-infected patients

• 2 Nucleotide reverse transcriptase inhibitors (nRTI) and efavirenz (a non-nucleotide reverse transcriptase inhibitor [nnRTI])

• nRTI - tenofovir/emtricitabine 300mg/200mg qDay

• nRTI - abacavir/lamivudine 600mg/300mg qDay

• Efavirenz 600mg PO Qhs (800mg for pt >60kg)

Considerations in regards to ART therapy in co-infected patients on rifampin

• Rifampin is a potent CYP3A4 inducers and may decrease serum concentrations of other medications, especially protease inhibitors (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI). PIs are CYP3A4 inducers and more study needs to be done to understand their interaction and effect on serum drug levels particularly in combination with rifampin.

• Nonnucleotide reverse transcriptase inhibitors:

  • Efavirenz based ART is recommended for co-infected patients with the dosage of efavirenz increased to 800mg/day for patients over 60kg.

  • Delavirdin should not be used together as AUC is decreased by about 95%.

  • Nevirapine serum levels are reduced by rifampin, although no safety data exists for increasing the dosage of nevirapine

• Single PI use with rifampin is not recommended. Ritonavir is the only PI that can be used with Rifampin. Ritonavir's area under the concentration curve (AUC), a measure of the bioavailability of a drug based on the serum concentrations over time, is reduced 35% by rifampin. Other PIs AUC's are reduced by greater than 80%.

• Dual PI combinations

  • Saquinavir/ritonavir would need to be increased to 400mg/400mg twice daily if taken with rifampin

  • Lopinavir/ritonavir shouldn't be used unless it is pharmaco-augmented for additional ritonavir twice daily, with increased hepatotoxicity from ritonavir likely.

• nucleoside analogs -

• Integrase inhibitors - No dosing changes are recommended, although raltegravir serum levels are reduced

• CCR5 receptor antagonists - maraviroc dosage should be increased when used with rifampin

Considerations in regards to ART therapy in co-infected patient on rifabutin

• Rifabutin is a substrate for CYP3A4, so its concentration may be effected by other medications that are CY3A4 inducers or inhibitors

• Rifabutin has complex interactions with other antivirals, and the interactions have not been well studied, so rifabutin is not generally recommended in this circumstance

• Protease inhibitors:

  • Rifabutin dosage should be reduced when used in combination with ritonavir and a PI, or with a PI alone,

  • Rifabutin shouldn't be used with squinavir alone.

• Nonnucleotide reverse transcriptase inhibitors:

  • Nevirapine and Rifabutin don't change dosages when used together

  • Increase dosage of rifabutin when used with efavirenz

  • Rifabutin and delavirdine shouldn't be used together

Posting #2 - Incidence and prevalence of HIV & TB globally and in the US

Epidemiology of Tuberculosis (TB):

• TB infection affects approximately 1/3 of the world's population, with 9.2 million new infections, and resulted in 1.7 million deaths in 2006 (World Health Organization [WHO], 2008).
  
• In the US, 13,299 new cases of TB were reported in 2007, and 644 deaths from TB were reported in 2006. A study in 1999-2000 estimated that 11.2 million people in the US have latent tuberculosis infection (LTBI; Bennett et al., 2008).
• The highest prevalence is in South and South-East Asia, followed closely by Sub-Saharan Africa.
• Poverty and malnutrition disproportionately affect women, leading to increased rates of TB disease in women. Tuberculosis is a leading killer of women between 15 and 44 years worldwide, with 1 million dying of TB per year. (World Health Organization [WHO], 2009).

Epidemiology of Human Immunodeficiency Virus (HIV):

• HIV affects approximately 33 million people worldwide, infected 2.7 million new people, and resulted in 2.0 million deaths in 2007 (World Health Organization [WHO], 2007a).
  
• In the US, an estimated 1.2 million people live with HIV in 2007 (World Health Organization [WHO], 2007b), 56,000 new cases of HIV infections occurred in 2006 (Hall, et al., 2008), and 22,000 people died of AIDS in 2007 (World Health Organization [WHO], 2007b).
• The highest prevalence is in Sub-Saharan Africa, outdistancing all other regions.
• Of those living with HIV worldwide, 47% are adult women and 6% are children under 15. 13.5% of those who die of AIDS are children under 15. In Sub-Saharan Africa, the hardest hit region, the estimated percentage of people receiving antiretroviral therapy has increased from 2006 to 2007, but is still only 30%.

Epidemiology of TB/HIV co-infection:

• 700,000 people globally live with a co-infection of HIV and TB (as of 2006), and it is estimated that 230,000 of co-infected people will die from their TB infection in 2008 . In the US, an estimated 1400 people developed a co-infection of HIV and TB, while 134 of co-infected people died of their TB infection in 2006 (World Health Organization [WHO], 2008). The numbers tested in 2006 are equivalent to 12% of TB case notifications globally, and 22% of notified cases in the African Region.
• The highest prevalence is in Sub-Saharan Africa.
• HIV is the main reason for not being able to meet WHO TB control targets worldwide. In Sub-Saharan Africa, HIV/AIDS is dramatically aggravating the epidemic of TB

References

Bennett, D. E., Courval, J. M., Onorato, I., Agerton, T., Gibson, J. D., Lambert, L., et al. (2008). Prevalence of tuberculosis infection in the United States population: The national health and nutrition examination survey, 1999-2000. American Journal of Respiratory Critical Care Medicine, 177, 348-55.

World Health Organization. (2007a). Global summary of the AIDS epidemic, December 2007. Retrieved 1/4/09 from http://www.who.int/hiv/data/en/

World Health Organization. (2007b). Epidemiological Fact Sheet on HIV and AIDS, United States of America. Retrieved from http://apps.who.int/globalatlas/predefinedReports/EFS2008/index.asp

World Health Organization. (2008). Global health atlas: Data query. Retrieved 1/1/09 from http://www.who.int/globalatlas/dataQuery/default.asp

World Health Organization. (2009). Frequently asked questions about TB and HIV. Retreived 7/20/2009 from http://www.who.int/tb/hiv/faq/en/

Tracy Maier