BY:SWATI SARIN

HIV AND TB CO-INFECTION

INTRODUCTIONAIDS (Acquired Immunodeficiency

Syndrome) is a retroviral diseaseCaused by the Human

Immunodeficiency Virus (HIV) Characterised by profound

Immunosuppression Opportunistic infectionsSecondary neoplasmsNeurological manifestations

HISTORY OF AIDS

AIDS , first reported in 1981 by CDC (Centre of Disease Control),US :

• 5 homosexual males displaying unusual infections:

• Fungal pathogen (Pneumocystis carinii) which causes pneumonia, kaposis sarcoma (rare skin tumor), deficiency in cellular immune response and decreased no. of T cells carrying CD4 marker.

In early 1982, CDC suggested the name AIDS to be given to disorder that results in decrease in CD4+ count

EPIDEMILOGY: GLOBAL CRISIS

Over 38,000,000 people around the world are diagnosed with HIV.

Top 5 countries:1.South Africa – 5,700,0002.Nigeria – 2,600,0003.India – 2,400,0004.Kenya – 1,900,0005.Zimbabwe – 1,800,00

This graph shows how much people would be affected with HIV in 2010.

This graph shows the percentage of the causes of HIV.

Human Immunodeficiency virus

In 1983,Causative agent of AIDS was discovered & characterized by group at Pasteur Ins. Of Paris-Luc Montagnier as a type of retrovirus isolated by lymph node biopsy of AIDS patientIn 1986, retrovirus was first named HIV

HIV : WHAT IS IT?

Scientist believe that HIV is the descendant of the Simian Immunodeficiency Virus (SIV). SIV is a lent virus that is found in animals like monkeys.

HIV-1 and HIV-2

HIV-1 global and HIV-2 discovered in West Africa and found principally in West Africa

HIV-2 more virulent, faster progression and associated with greater morbidity

ROUTES OF SPREAD Sexual Contact – 75% Parental Inoculation – intravenous drug abusers

and recipients of blood and blood products. Passage of virus from Infected mothers to children

through the placenta or through breast milk.

HIGH RISK GROUPS

•Homosexuals/ Bisexuals• Intravenous drug users• Infants born to infected mothers• Blood & Blood component recipients (through Transfusion)• Hemophiliacs

TRANSMISSION OF HIV VIRON TO T CELLS

PHASES OF HIV INFECTION

Early, acute

Middle, chronic

Final, late

Group I : Acute Infection

lasts about 2 weeks

Fever, aches, and other flu-like symptoms

High levels of virus in the blood.

Group II: Asymptomatic Infection

Group III: Persistent generalised lymphadenopathy

Lasts for months or even years Few symptoms The patient's blood contains few viruses, but contains

antibodies to the virus

Group IV: AIDS

A rapid decline in the number of CD4+ T cells.

The patients immunity is sufficiently weakened that opportunistic infections

viruses, e.g., Herpes simplex, Epstein-Barr virus (EBV)

bacteria, e.g., Mycobacterium tuberculosis

fungi, e.g. Candida albicans

Opportunistic infections become more severe and cancer e.g, lymphoma,Kaposi's sarcoma)may develop.

SEROLOGIC PROFILE

OF AIDS PATIENT

BIOMARKERSPresence of Anti HIV Antibodies

Decrease in number of CD4+ T cells

Presence of serum protein p24 by ELISA & RIA

Absent of delayed hypersensitive reactions

Occurrence of opportunistic infections

TREATMENT IN AIDS1. Nucleoside analogs: Reverse transcriptase inhibitors: Zidovudine (Retovir,AZT), Didanosine (Videx,ddI) Lamivudine (Epivir, 3TC) Statuvidine (d4t)

2. Nonnucleoside analogs: Reverse transcriptase inhibitors: Nevirapine

3. Protease Inhibitors: Indinavir

4. Combination therapy- HAART) (highly active anti retroviral therapy) 2 nucleoside analog (AZT, ddI) + protease inhibitor (Retrovir)

5. Clinical trials vaccine has been found in monkeys but none yet available for human use.

Prolongs survival but does not eliminate the virus Inhibits proviral DNA synthesis but does not eliminate the virus.

Inhibits action of reverse transcriptase

PULMONARY TUBERCULOSIS

Deadly infectious disease caused by Mycobacterium tuberculosisFirst isolated in 1882 by a German physician named "Robert Koch" who received the Nobel Prize for this discovery

EPIDEMILOGY According to the World Health Organization (WHO),

nearly 2 billion people—one third of the world's population—have been exposed to the tuberculosis pathogen.

Annually, 8 million people become ill with tuberculosis, and 2 million people die from the disease worldwide.

Tuberculosis is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with HIV/AIDS .

PATHOGENESIS

Droplet nuclei containing tubercle bacilli are inhaled, enter the lungs, and travel to the alveoli

Tubercle bacilli multiply in the alveoli

A small number of tubercle bacilli enter the bloodstream and spread throughout the body. The bacilli may reach any part of the body, including areas where TB disease is more likely to develop (such as the lungs, kidneys, brain, or bone

Macrophages form a hard shell & keeps bacilli under control

SYMPTOMSTB may be pulmonary or extra-pulmonary

Pulmonary TB is most common form

DIAGNOSIS OF TB

Injection of Protein: found in TB bacteria into the skin of an arm, skin reacts by swelling

X-ray

Sputum test

Bacteria: A culture of TB bacteria

M. tuberculosis (stained red) in sputum

Abnormalities often seen in posterior segments of upper lobe

TREATMENT IN TB

1. ethambutol is EMB or E,

2. isoniazid is INH or H,

3. pyrazinamide is PZA or Z,

4. rifampicin is RMP or R,

5. combination of antibiotics- Streptomycin is STM or S. Surgery

DRUGS:

PREVENTIVE MEASURES:

1.Vaccine BCG2.Covering of mouth by a mask3.Exercise regularly to keep your immune system healthy4.Get adequate amounts of sleep5.Get tested regularly..6.Make sure you eat plenty of healthy foods7.A drug called Isoniazid (INH) can be used as a preventative therapy for those who are at high risk of becoming infected with tuberculosis

EHZRS

HIV AND TB(Interaction & Co-infection)

HIV infection increases the likelihood that new infection with M. tuberculosis (due to immune suppression) will progress rapidly to TB disease.

Among HIV-infected individuals, lifetime risk of developing active TB is 50%, compared to 5-10% in persons who are not HIV-infected.

In a person infected with HIV, the presence of other infections, including TB, allows HIV to multiply more quickly. This may result in more rapid progression of HIV infection

DIAGNOSIS OF TB IN HIV AIDS

Frequently negative sputum smearsAtypical radiographic findingsResemblance to other opportunistic pulmonary

infections like pneumonia

WHY is it difficult to diagnose TB in HIV infected patient

Arrow points to cavity in

patient's right upper lobe

--typical finding in

patient with TB

CT scan and magnetic resonance imaging (MRI)

Peripheral blood cultures

Molecular diagnostic techniques based on detection of M. tuberculosis specific DNA or ribosomal RNA sequences by polymerase chain reaction (PCR)

FURTHER DIAGNOSTIC TECHNIQUES IN HIV TB CO-

INFECTION

TREATMENT OF HIV & TBHIV infected patients should be treated according to national guidelines and in cooperation with local authorities such as the district medical officer (DMO) and the district TB supervisor.

Treatment of TB always takes precedence over the treatment of HIV infectionAims of treatment

To cure the patient of TB To prevent death from active TB or its late effects To prevent TB relapse To decrease TB transmission to others

WHO Recommended TB treatment regimen

Drug regimens Initial phase- first 2-3 months

During the initial phase, there is rapid killing of TB bacilli Three or more drugs are used in combination Infectious patients become non-infectious within about 2 weeks

and symptoms usually improve

Continuation phase- additional 4-6 months• Fewer drugs are necessary (usually 2), but longer time

• These drugs eliminate the remaining bacilli

Directly Observed Treatment Strategy (DOTS)DOTS is a strategy for TB control which aims to detect 70 percent

of active TB cases and to successfully treat 85 percent of them Monitoring during treatment--way to ensure patient adherence

where a trained supervisor watches the patient swallow the drugs

WHO Recommended TB treatment regimen

Some Authorities recommend 7 month continuation phase with daily isoniazid and rifampicin (7HR) for patients with various forms of disease: TB meningitis, spinal TB with neurological signs

2 HRZE / 6 HE: This is a common regimen - initial phase- 2 months with isoniazid (H), rifampicin (R), pyrazinamide (Z), and ethambutol (E). continuation phase is 6 HE isoniazid (H) and ethambutol (E)

4 H3R3 : 4 months-3 times a week- Initial phase is 2 H3R3Z3E3 The continuation phase is 4 H3R3

Antiretroviral Therapy for Individuals with Tuberculosis

Co infectionWHO Recommendations for ARV Therapy

WHO recommends that people with TB/HIV complete their TB therapy prior to beginning ARV treatment unless there is high risk of HIV disease progression and death during the period of TB treatment.

In cases where a person needs TB and HIV treatment concurrently, first line treatment options include ZDV/3TC or d4T/3TC+Niverapine

ZDV: Zidovidine3TC: Lamivudined4t: Stavudine

HIV-TB CO-INFECTIONHIV-TB CO-INFECTION Clinical trials:Clinical trials:

Where’s the momentum?Where’s the momentum?

Which HAART regimen? 2 NRTIs + 1 PI ? 2 NRTIs + 1 NNRTI? 3 NRTIs?

Nevirapin 400 or 600 mg? Nevirapin or efavirenz?

When to start HAART?

NVP 400/600 STUDYA 48 week, randomized, open-label, 2 arm study to compare the

efficacy, safety and tolerability of HAART containing nevirapine

400mg/day vs. nevirapine 600 mg/day in HIV-1 infected

patients started at 2-6 weeks after initiating rifampin containing

antiTB therapy: NCT 00476853, ThailandThailand.

CD4 < 200. Proven TB.

Primary outcome: HIV-1 RNA quantification in plasma at W 48.

Started in October 2005.

Target n=100.

Date of completion: October 2008.

NVP/EFZ INDIAN STUDYSafety and efficacy of 2 once daily anti retroviral treatment regimens along with anti-TB treatment: NCT 00332306, IndiaIndia.

CD4 < 250

HAART begun at the end of intensive phase of anti-TB Rx (2EHRZ3/4RH3). ddI + 3TC + NVP vs. ddI + 3TC + EFZ.

Primary outcome: suppression of VL to < 400 copies/ml at the end of 6 months and a VL<400 copies/ml at 24 months of HAART.

Started in June 2006.

Target n=180.

Date of completion: December 2009.

TB-HAART STUDYAn evaluation of the impact of early initiation of HAART on TB treatment outcomes for TB patients coinfected with HIV: ISRCTN77861053, Uganda, Uganda,

Zambia, South Africa and TanzaniaZambia, South Africa and Tanzania. 220 < CD4 < 500.

Study hypothesis: early concomitant treatment with TB and HIV medications may improve TB outcomes and improve survival.

Primary outcome: proportion of subjects reaching the composite endpoint of treatment failure or death at 6 months after the initiation of short-course chemotherapy for TB.

Combined HAART with anti-TB vs. delay HAART at 6 months.

Started in March 2007.

Target n=1900. Actual enrollment: 33.

Date of completion: 2011.

AZT + 3TC + efavirenz

CONCLUSICONCLUSIONON

However, still some gaps are remaining ???

REFERENCES Kindt T J, Goldsby R A, Osborne B A: Immunology, Pg No.

525-544

http//www.avert.orghttp//www.health.am/

symptoms.comajrcmb.atsjournals.orgwww.ncbi.nlm.nih.gov › ... › Clin Microbiol Rev ›

v.16(3); Jul 2003 www.who.int › ... › TB/HIVwww.sciencedaily.com/releases/

2009/03/090324131600.htm www.ncbi.nlm.nih.gov/pubmed/15817963 medind.nic.in/nac/t03/i3/nact03i3p11.pdf

QUESTIONS??QUESTIONS??

THANK YOU

“WE CAN’T FIGHT AIDS UNLESS WE DO MUCH MORE TO FIGHT TB AS WELL”NELSON MANDELABANGKOK, JULY 2004