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.
The Co-infection TB / HIV: TB, infectious disease caused by Mycobacterium tuberculosis (Mtb), is highly prevalent among HIV-infected population, especially in countries with high burden of tuberculosis, such as Brazil. In our country, TB is the leading cause of death by disease set in PVH. This is due to the fact that the defense against the development of TB disease is directly related to cellular immunity preserved precisely the mechanism that is progressively destroyed by HIV. People infected with Mtb may develop signs and symptoms of disease (disease TB or active TB) soon after infection, sick long after the primary infection, or even never have active tuberculosis. The persistence of the bacillus in the body, in latent form, is called latent TB infection or latent TB infection (LTBI). This latency period, the infected person is asymptomatic and does not transmit TB. Compared to people with a good immune performance, the risk of latent infection manifest as active disease is the 20 30 times in PVH.1 And the more severe the immune compromised individual, the less responsive, so that patients with lymphocytes TCD4 less than 200 cells / uL have six times greater risk of developing active TB than those with CD4 above 500.2 in São Paulo, 78,7% of TB patients tested for HIV coinfection in 2015 was 8,3 .3% this year cohort analysis of data showed that, among the TB cases in 2096 HIV + 469 (22,4%) died during treatment of TB. Death, according to some studies have shown, occurs in the first two months of treatment, which is why the rapid diagnosis of TB is critical and it is essential to
Diagnosis of HIV among those with TB. The good news is that there are important and effective weapons that can prevent active disease manifests itself: antiretroviral therapy (ART) and treatment of latent TB infection. With respect to ART has been shown in a study conducted in Brazil in the last decade and under programmatic conditions, that treatment for HIV directly impacts the developing TB, with a reduction of 80% in patients treated with highly active antiretroviral therapy ( HAART) compared to naive patients TARV.4 Another study, also conducted in our country, it showed that the combination of the two strategies - treatment of LTBI and ART - significantly reduces the incidence of tuberculosis, both in the more immunologically compromised patients and in those at the early stages of infection HIV.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:
✓ chest radiography, where ✓ rapid molecular test for tuberculosis (TB-TRM) 6: DNA molecular method that detects Mtb complex and rifampicin resistant strains by polymerase chain reaction (PCR) in real time. Demand only 01 sputum samples and about two hours to result. Since the test identifies genetic material from living or dead bacilli, is not indicated for follow-up treatment of TB and to diagnose or treatment cases (relapses and returns after default). Indications: • primarily for the diagnosis of pulmonary TB and larynx in breathing materials: sputum, induced sputum, washed alveolar bronco, tracheal secretions. • in patients with suspected failure of the basic scheme for early identification of rifampicin resistance. • in cases of retreatment for rifampicin resistance screening. • it can be used for diagnosis of some extrapulmonary forms: CSF, lymph nodes and other tissues material in special laboratories and through specific preparation techniques. Notes: • concurrently with the TRM request, you must also request culture, identification and susceptibility testing for other drugs, both new cases of TB and to
Retreatment for any form of tuberculosis. ✓ For blood samples and those from punctures and biopsies - and if it was not done TRM-TB - request smear (if indicated), culture for mycobacteria, identification and sensitivity testing ✓ Other imaging tests (ultrasound, CT computed), depending on each case. ✓ Anatomopathologic
INFECTION SCREENING LATENT TUBERCULOSIS IN PVH: WHY, WHEN, WHERE AND HOW TO DO IT WHY: the treatment of LTBI reduces the risk of active TB. When: for all asymptomatic patients ✓ At the beginning of follow-up, ✓ ✓ In immune reconstitution and annually for those with negative tuberculin skin test and no previous treatment for LTBI or active TB. WHERE: for medical consultation HOW DO IT: ✓ Make sure that the patient is asymptomatic. ✓ Request: chest X-ray and tuberculin test with purified protein derivative (PPD) as initial screening tests, noting that:
- the CD4 count is low, PPD below 5mm (non-reactive) should be repeated when the immune recovery • to any CD4 count PPD nonreactive must be repeated each year • if the current PPD or previous ≥ 5mm, there is no need repeat this test; continuing to conduct treatment LTBI ✓ When available, interferon-gamma release assay (IGRA) can replace the 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 radiography E: • PPD ≥ 5mm OR; • household or institutional contacts of smear positive patients, regardless of PPD; OR • PPD <5mm with documentary record of having had PPD ≥ 5mm and not subjected to the treatment of active or latent TB at the time. 2. Chest radiography with presence of radiological scar TB without previous treatment for TB (remote possibility of active TB through sputum tests, radiographs and, if necessary, computed tomography), regardless of the outcome of the PPD.
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 who are in use of protease inhibitors (PI) should replace rifabutin 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 TB drugs. drug Clearance 50-90 creatinine clearance creatinine 10-50 Clearance creatinine <10 Hemodialysis Monitor adverse effects R not necessary Setting not necessary Setting not necessary Setting not necessary Setting Hepatotoxicity interstitial nephritis, thrombocytopenia, leukopenia, eosinophilia, hemolytic anemia, neutropenia, vasculitis H Set not necessary not necessary Setting not necessary Setting make the post dialysis dose Hepatotoxicity, vasculitis, sensorineural Z changes as table 1 not necessary Set alternate Days Days alternate, perform post dialysis dose Hepatotoxicity, arthralgia, myalgia, rhabdomyolysis / mioglobiunúria / renal failure; As 1 and 24-frame every alternate day 36 hours 15mg / kg every other day to post dialysis dose optic neuritis R = rifampicin; H = Isoniazid; Z = Pyrazinamide; E = ethambutol.
Contin. Table 3 - Doses and most relevant adverse effects of TB drugs. medicament creatinine clearance 50-90 creatinine clearance 10-50 creatinine clearance <10 Dialysis Monitor adverse effects Streptomycin 15mg / kg 1x day 15mg / kg every 24-72h 15mg / kg every 72-96h 15mg / kg every 72-96h and 7,5mg extra dose / kg Hypoacusis after dialysis, dizziness, nystagmus Levofloxacin 750mg / day 750mg alternate days, alternate days later 500mg 750mg after 500mg other day 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 pattern containing efavirenz + lamivudine + ✓ RHZE tenofovir + raltegravir, depending on ARV use history or according to genotyping. ✓ rifabutin HZE + IP-containing regimen
inflammatory syndrome of immune reconstitution The lower the CD4 count and the earlier the introduction of HAART, the greater the risk of immune reconstitution inflammatory syndrome (IRIS). IRIS constitutes radiological and clinical worsening in patients who had presented concomitant with clinical improvement and decrease in viral load and lifting CD4. It occurs within three months after the introduction of HAART and lasts on average 02 months. May present with fever, cough return, increase and fistula of nodes, radiological worsening, among other signs / sintomas.8 The table is usually self-limited, with corticoid use of benefit to more exacerbated frames. The mortality is low and IRIS generally related to events in the central nervous system (CNS), with herniation, and hydrocephalus. For this reason, it is recommended that the introduction of HAART in TB patients in CNS is 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, M Morgan, Jamal L, K Laserson Barrier D, Smith L, Santos J, Wells C, Paine R, Garrett D. Impact of antiretroviral therapy on the incidence of tuberculosis: the Brazilian experience, 1995-2001. PLoS One 2007 5 Sep; 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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