INTRODUCTION: This guide is designed to be an easily accessible and handling material, so that the health professional service specializing in care for people living with HIV (PLHIV) have the basic information about prevention, screening, diagnosis and treatment of tuberculosis ( TB) in the PVH, its impact and its importance in the transmission chain of the disease.
TB / HIV Coinfection: TB, an infectious disease caused by Mycobacterium tuberculosis (Mtb), is highly prevalent among the HIV-infected population, especially in countries with a high tuberculosis burden, such as Brazil. In our country, TB is the main cause of death, due to defined disease, in HPV. This is due to the fact that the defense against the development of TB disease is directly related to preserved cellular immunity, precisely the mechanism that is progressively destroyed by HIV. People infected with Mtb can develop signs and symptoms of the disease (tuberculosis disease or active TB) soon after infection, get sick long after the first infection, or even never have active tuberculosis. The persistence of bacilli in the body, in latent form, is called latent tuberculous infection, or latent TB infection (ILTB). In this latency period, the infected person is asymptomatic and does not transmit TB. When compared to people with good immune performance, the risk of latent infection manifesting as an active disease is 20 to 30 times higher in HPV.1 And the more severe the individual's immune compromise, the less responsiveness, so that patients with TCD4 lymphocytes lower than 200 cells / μL present a six-fold higher risk of TB disease than those with CD4 above 500.2 In the state of São Paulo, with 78,7% of TB patients tested for HIV, 2015 coinfection was 8,3 % .3 Analysis of cohort data from that year showed that 2096 among 469 cases of HIV + TB, 22,4 (XNUMX%) died during TB treatment. According to some studies, death has occurred in the first two months of treatment, which is why rapid diagnosis of TB is fundamental, as is the
Diagnosis of HIV among those with TB. The good news is that there are important and effective weapons that can prevent active disease from manifesting itself: antiretroviral therapy (ART) and treatment of latent TB infection. Regarding HAART, a study conducted in Brazil in the last decade and under programmatic conditions has shown that treatment for HIV has a direct impact on TB illness, with a reduction of 80% in patients treated with high-potency antiretroviral therapy ( HAART) when compared to ART-naive patients.4 Another study, also conducted in our country, showed that the combination of the two strategies - treatment of ILTB and HAART - significantly reduces the incidence of tuberculosis in both more immunologically compromised patients and in those in the earliest stages of HIV infection.5
TRACKING TB ACTIVE IN PVH: WHY, WHEN, WHERE AND HOW TO DO IT WHY: PVH has increased risk for developing active TB, which is the leading cause of death in this population. The death in TB-HIV co-infection occurs mainly in the early treatment of TB, making urgent diagnosis and early treatment. WHEN: At every opportunity, for all HPV, regardless of previous treatment for TB. The questioning of fever, cough, weight loss or night sweats should be done on every unit to visits by any health professional. WHERE: the key questions above may be part of the risk assessment in trials, for example, followed by referral to medical care when needed. HOW TO DO IT: actively question signs or symptoms suggestive of active TB: fever, cough, weight loss or night sweats. In presence
Any of these symptoms, or any other that suggests TB, initiate research, requesting specific tests, depending on the symptoms and / or affected organ:
✓ X-ray molecular test for TB (TRM-TB) 6: molecular method that detects DNA from the Mtb complex and resistant strains of rifampicin by the real-time polymerase chain reaction (PCR) technique. It only requires 01 sputum samples and about two hours for result. As the test identifies genetic material from living or dead bacilli, it is not indicated for follow-up of TB treatment or for the diagnosis of retreatment cases (relapses and re-admissions after abandonment). Indications: • primarily for the diagnosis of pulmonary and laryngeal TB, in respiratory materials: sputum, induced sputum, bronchoalveolar lavage, tracheal secretion. • in patients with suspected failure of the basic regimen, for the early identification of resistance to rifampicin. • in cases of retreatment, for screening for resistance to rifampicin. • can be used for the diagnosis of some extrapulmonary forms in: cerebrospinal fluid, lymph node material and other tissues, in special laboratories and through specific techniques of preparation. Observations: • Concomitantly with the MRT request, culture, identification and sensitivity testing should also be requested for other drugs, both for new TB cases and for
Retreatments, for any form of tuberculosis. ✓ For blood samples and those from punctures and biopsies - and if TRM-TB has not been done - request smear microscopy (when indicated), culture for microbacteria, identification and sensitivity test ✓ Other imaging tests (ultrasonography, tomography computerized), depending on each case. ✓ Anatomopathological
TRAINING OF LATENT TUBERCULOSIS INFECTION IN HVP: WHY, WHEN, WHERE AND HOW DO IT DO IT: Treatment of ILTB decreases the risk of active TB. WHEN: for all asymptomatic patients ✓ At the beginning of follow-up, ✓ On immunological reconstitution and ✓ Annually, for patients with negative tuberculin test and no previous treatment for ILTB or active TB. WHERE: in medical consultations HOW TO DO IT: ✓ Make sure the patient is asymptomatic. ✓ Request: Chest X-ray and purified protein derivative tuberculin test (PPD) as initial screening tests, noting that:
- if CDXUMUMX count is low, PPD below 4mm (non-reactor) should be repeated upon immunological recovery • with any count of CD5, PPD non-reactor should be repeated annually • if PPD current or previous ≥ 4mm, no need for if you repeat this test; continue treatment for ILTB treatment ✓ When available, the interferon-gamma release (IGRA) test may replace PPD.
INFECTION TREATMENT OF LATENT TUBERCULOSIS Only after being ruled out active TB should be instituted treatment for LTBI. Treatment of LTBI is no urgency, and until there is clinical and laboratory data to ensure that the patient is not ill with active TB, you should not start treatment of LTBI. Therefore, note that:
- Normal chest X-ray E: • PPD ≥ 5mm OR; • intradomiciliary or institutional contacts of bacilliferous patients, regardless of PPD; OR • PPD <5mm with documentary record of having had PPD ≥ 5mm and not undergone active or latent TB treatment at the time. 2. Chest X-ray with presence of radiological scar of TB, without previous treatment for TB (apart from the possibility of active TB by means of sputum exams, previous radiographs and, if necessary, computed tomography of the chest), independently of the PPD result.
Having met the criteria above, starting 10mg isoniazid / kg day, the maximum dose 300mg / day for the 6 9 months. complete are considered the treatments with 180 taken over 09 270 months or taken over 12 months.
CALL PRIORITIZATION Ideally, treatment of TB-HIV co-infection must be done by the same team and the same place in an integrated manner. Treatment of active TB is urgent and immediate diagnosis. In severe cases, it can even be established empirically, after collecting all appropriate materials for smear, TRM-TB culture and histopathological examination. Patients who come to the service already with TB diagnosis must be met as a priority and if TB treatment not yet started, this should happen on the first visit to the service. Patients with HIV and TB should be reevaluated periodically, ideally at two weeks after initiation of treatment and time of not less than 30 days thereafter. When necessary, they should be reviewed at shorter intervals, according to the needs of each case.
INFECTION CONTROL MEASURES Priority should be given the care of patients with active tuberculosis or respiratory symptoms with suspected TB, preferably wearing surgical masks, your accommodation in waiting rooms and well ventilated offices with air flow to the outside of the unit and, possible, with sunshine input, are measures that help to minimize the risk
TB transmission in health facilities. Health professionals should use masks N95 wherever indicated, especially in the rooms of patients with active tuberculosis or pulmonary TB research and in bronchoscopy rooms. Masks should always be well adjusted to be effective and should only be taken when the trader out of the risk area. Yet for protection of health professionals, it is recommended that they also may be screened annually for LTBI with conducting annual PPD for non reactors and treatment of LTBI when indicated. The prompt suspicion of active TB in this group is also key to individual and collective protection.
ACTIVE TREATMENT OF TUBERCULOSIS
In naive patients ARV, treatment of active TB always precedes the onset of ART. For patients using antiretroviral drugs at diagnosis of TB, ART should not be stopped, but only adjusted when necessary.
Schemes for TB treatment, dosages and adverse effects are known MTB sensitive to rifampicin, the TRM-TB diagnosed or absence of this examination, TB should preferably schemes contemplate the use of rifamycins (rifampicin or rifabutin). Ideally, TB treatment should be done with the basic scheme, by using the combined tablets of rifampicin, isoniazid, pyrazinamide and ethambutol (RHZE). Note always adjust the dose according to the patient's weight.
Table 1 - Basic scheme with rifampicin for TB treatment in adults and adolescents (> 10 years old)
For patients taking protease inhibitors (PIs), rifabutin should be substituted for rifampicin:
Table 2 - Basic scheme with rifabutin to treat tuberculosis in adults and adolescents (> 10 years old)
Isoniazid * - 10 mg / kg / day, the maximum dose of 300 mg / day; pyrazinamide - 35 mg / kg / day, the maximum dose of 1.500 mg / day; ethambutol - 25 For the treatment of tuberculous meningoencephalitis, it is still recommended corticosteroid association antiTB scheme: oral prednisone
(1 -2 mg / kg / day) for four weeks or intravenous dexamethasone in severe cases (the 0.3 0.4 mg / kg / day) for four to eight weeks, with a gradual reduction of the dose within four weeks. Furthermore, the maintenance phase should be extended to 07 months, totaling 09 months of treatment. For patients with non-compensated liver disease, it is recommended that treatment with alternative scheme: streptomycin, ethambutol, and levofloxacin. 60 are planned doses of streptomycin, being able to not apply this medicine on weekends.
Table 3 - Doses and most relevant adverse effects of drugs for TB. drug Clearance creatinine 50-90 Clearance creatinine 10-50 Clearance creatinine <10 Hemodialysis Monitor adverse effects R Adjustment not necessary Adjustment not necessary Adjustment not necessary Adjustment not required Hepatotoxicity interstitial nephritis, thrombocytopenia, leukopenia, eosinophilia, haemolytic anemia, neutropenia, vasculitis H Adjustment not necessary Adjustment not necessary Adjustment not necessary Adjust dialysis dose Hepatotoxicity, vasculitis, sensorineural changes Z As a table 1 Adjustment not required Alternate days Alternate days, dose post dialysis Hepatotoxicity, arthralgia, myalgia,, rhabdomyolysis / myoglobinuria / renal failure, E As a 1 frame At each 24-36 hours Alternate days 15mg / kg alternate days, do the post-dialysis dose Optic neuritis R = rifampicin; H = isoniazid; Z = pyrazinamide; E = ethambutol.
Contin. Table 3 - Doses and most relevant adverse effects of drugs for TB. 50 / 90h 10h / 50h 10 / 15h 1 / kg 15 / 24h 72h / 15h / 72h / 96h 15 / 72h / 96h / 7,5h / 750h / Dose of 750mg, then 500mg Alternate Days 750mg, then 500mg Alternate Days Nausea, diarrhea (associated with C. difficile), tendinopathy, arthralgia, myalgia, paresthesias, confusion mental, hallucinations.
As framework 2
Clearance <30: recommended to reduce the dose by half. However, rifabutin only available in capsules.
Rash, neutropenia, leukopenia, thrombocytopenia, nausea, abdominal pain, uveitis
R = Rifampicin; H = Isoniazid; Z = Pyrazinamide; E = ethambutol. It is important to be aware of the occurrence of adverse effects to drugs, monitoring transaminases, renal function and blood count periodically. The management of adverse reactions depends on its severity and medicines to them. In severe cases, it is suggested the suspension of the whole scheme, with its staggered reintroduction drug the drug as soon as possible. In situations of resistance or intolerance to one or more drugs of the basic scheme, it should be discussed case by case; In principle, however, one can follow the guidelines in the table below.
Table 4 - ducts in the impossibility of using a antiTB drug in the impossibility of using possible options rifamycin (rifampicin or rifabutin) resistance discuss a case rifamycin (rifampicin, rifabutin), for intolerance or monoresistance confirmed 2HZES / 10 HE * Streptomycin may be replaced by a fluoroquinolone, which is used in both phases of isoniazid treatment (at monoresistance or intolerance) 2RZES / 4RE pyrazinamide (in monoresistance or intolerance) 2RHE / 4RH Ethambutol (in monoresistance or intolerance) 2RHZ / 4RH * nomenclature carries the number of months, and the abbreviation of each product: R = rifampicin, isoniazid = H, Z = pyrazinamide, and ethambutol = S = streptomycin.
opportune moment ART The introduction of HAART should be done in a timely manner, and one should wait at least two weeks after starting TB treatment. For patients with severe immunosuppression (CD4 below 200 cells / ul), ART should be introduced at the end of 2ª TB treatment week. For patients with 4 CD200 ≥ cells / ul, ART should be started after the end of the intensive phase of TB treatment (after 08 weeks).
antiretroviral regimens and treatment TB7 For patients starting TB treatment, ART virgins or who are not on ART, and since any previous exposure to ART permits, should be treated with the preferred scheme:
RHZE + lamivudine + tenofovir + raltegravir (400mg 12 / 12h) (raltegravir should be replaced by dolutegravir the end of TB treatment) for patients previously exposed to ART or already in HAART for the diagnosis of TB are possible combinations:
✓ RHZE + scheme containing efavirenz ✓ RHZE + lamivudine + tenofovir + raltegravir, depending on the history of ARV use or according to genotyping. ✓ Rifabutin HZE + scheme containing IP
Immune reconstitution inflammatory syndrome The lower the CD4 count and the earlier the introduction of ART, the greater the risk of inflammatory immune reconstitution syndrome (SIRI). SIRI consists of clinical and radiological worsening in patients who were presenting clinical improvement and had a decrease in viral load and elevation of CD4. It occurs within three months after the introduction of ART and lasts, on average, 02 months. It may present with fever, cough return, enlargement and fistulization of the ganglia, radiological worsening, among other signs / symptoms.8 The picture is usually self-limited, with the benefit of using corticosteroids for the most exacerbated pictures. SIRI mortality is low and is generally related to manifestations in the central nervous system (CNS), with hydrocephalus and herniation. For this reason, it is recommended that the introduction of ART in patients with CNS TB be postponed for two months until the end of the intensive phase of TB treatment.
BIBLIOGRAPHY: Recommendations for the management of TB-HIV co-infection in specialized care services for people living with HIV / AIDS. Ministry of Health. Executive Secretariat- Brasília: Ministry of Health, 2013. Available at: http://bvsms.saude.gov.br/bvs/publicacoes/ recomendacoes_manejo_coinfeccao_tb_hiv.pdf
Manual of recommendations for the control of tuberculosis in Brazil / Ministry of Health, Secretariat of Health Surveillance, Department of Epidemiological Surveillance. - Brasília: Ministry of Health, 2011. Available at: http://bvsms.saude.gov.br/bvs/publicacoes/ manual_recomendacoes_controle_tuberculose_brasil.pdf
Clinical Protocol and Therapeutic Guidelines for Management of HIV Infection in Adults. Ministry of Health, Department of Health Surveillance. Department of STD, AIDS and Viral Hepatitis. Brasília, 2013 (updated in 2015). Available at: http: // www. aids.gov.br/sites/default/files/anexos/publicacao/2013/55308/protocolofinal_31_7_2015_pdf_31327.pdf
REFERENCES: 1. WHO. "Tuberculosis and HIV". [Internet]. Geneva: [Quoted 1Ouct2016]. Available at: http://www.who.int/hiv/topics/tb/about_tb/en/
- Golub JE, Cohn S Saraceni V, et al. Long-term protection from isoniazid preventive therapy for tuberculosis in HIV-infected Patients in the medium-setting burden tuberculosis: the TB / HIV in Rio (THRio) study. Clin Infect Dis 2015, 60: 639-45.
- Ministry of Health. Epidemiological Bulletin - Brazilian perspectives for the end of tuberculosis as a public health problem [Internet]. Brasilia: Ministry of Health, Department of Health Surveillance - Volume 47 (13), 2016 [Cited 5Mar2017]. Available at: http://portalarquivos.saude.gov.br/images/pdf/2016/marco/24/2016-009Tuberculose-001.pdf.
- Miranda A, Morgan M, Jamal L, Laserson K, Barreira D, Silva G, Santos J, Wells C, Paine P, Garrett D. Impact of antiretroviral therapy on the incidence of tuberculosis: the Brazilian experience, 1995-2001. PloS One. 2007 Sep 5; 2 (9): e826.
- Golub JE, Saraceni V, Choi SC, et al. The impact of antiretroviral therapy and isoniazid preventive therapy on tuberculosis incidence in HIV-infected Patients in Rio de Janeiro, Brazil. AIDS 2007, 21: 1441-8.
- Ministry of Health. Information Bulletin No. 09 / 2014, CGPNCT / DEVEP / SVS / MS: Recommendations on the diagnosis of tuberculosis through the rapid molecular test for tuberculosis. Available at: https://drive.google.com/file/d/0B0CE2wqdEaRdnZ6aVJBb1JKSTQ/view
- Ministry of Health. Information Note no. 007 / 2017 - DDAHV / SV / SMS. Available at: http://www.aids.gov.br/sites/default/files/anexos/legislacao/2017/59412/nota_ informativa_007_protocolo_de_uso_arv_2017_29907.pdf
- Meintjes G Lawn SD, Scano F, et al. Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. Lancet Infect Dis 2008, 8: 516-23
São Paulo 2017
Ministry of Health of São Paulo Coordinator Reference Center for Disease Control and Training STD / AIDS - SP / State Program of STD / AIDS in Sao Paulo. Division of Tuberculosis - Epidemiological Surveillance Center (CVE)
Coordination of the State Program of STD / AIDS-SP Maria Clara Gianna - Coordinator Artur Kalichman Olhovetchi and Rose Alencar Souza - Deputy Coordinators
Division of Tuberculosis Vera Maria Neder Galesi - Coordinator
Preparation Ana Angélica Bulcão Portela Lindoso - Division of Tuberculosis Leda Fatima Jamal - CRT-DST / AIDS Sumire Sakabe - CRT-DST / AIDS
Denize collaboration Lotufo José Ramalho Valdez Madruga
proofing Emi Shimma - Media Relations / CRT-DST / AIDS
Graphic Design, Cover, Layout Denis Delfran Pereira - Institutional Communication Center - CRT-DST / AIDS
São Paulo - 2017 Electronic version available at: http://www.saude.sp.gov.br/centro-de-referencia-etreinamento-dstaids-sp/publicacoes/publicacoes-download
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