HIV TB coinfection

HIV is a type of retrovirus that infects CD4+ T-cells, by merging irreversibly with the cellular genetic material, in human beings. After invading these helper T-cells, by varying mechanisms, the virus causes the destruction of  CD4+ T-cells. A steady decline in the population of these cells leads to loss of cell-mediated immunity conferred by them. And opportunistic infections occur in this state of reduced immunity. The typical opportunistic infections include:

• Candidiasis (a white-coloured fungal infection that can affect the skin, nails and mucous membranes of the mouth and vagina)
• Herpes simplex infections (cold sores around the mouth or genital ulcers)
• Kaposi’s sarcoma (cancerous skin lesions)
• Pneumocystis pneumonia (caused by a fungus known as Pneumocystis jirovecii)
• Tuberculosis 

Tuberculosis is an infectious disease caused by the bacteria Mycobacterium tuberculosis. While typically a respiratory disease (spreads by air and droplet transmission) affecting the lung, it can affect various other parts of the body as well. Examples of extra-pulmonary (outside the lungs) tuberculosis include abdominal tuberculosis, tubercular osteomyelitis (bone infection), tubercular meningitis (infection of covering of the brain), etc. Most tubercular infections are asymptomatic, or latent infections, as even after entering human cells, the bacteria do not cause disease. Thus, in states of chronic ill-health or other conditions (like HIV) in which the body’s immune system has taken a hit, due to lowered defences, the bacteria invade cells and cause active infection. 

Usual symptoms of tuberculosis include:

• Chronic cough (typically longer than two weeks) with sputum that may be blood-tinged
• Persistent fever
• Night sweats
• Significant weight loss (with noticeable loosening of clothes, rings or slippers or documented involuntary reduction in weight by at least 5% over six to 12 months)
• Breathlessness
• Chest pain
• Fever
• Weakness
• Fatigue

Tuberculosis is a largely preventable disease for which the BCG vaccine exists. Treatment for uncomplicated tuberculosis infection consists of quadruple antibiotic drug therapy with rifampicin, isoniazid, pyrazinamide and ethambutol.

However, with the increased use of these drugs, tuberculosis-causing bacteria have developed resistance against them. Therefore, in cases of drug-resistant tuberculosis—multidrug-resistant tuberculosis (MDR-TB) or extensively drug-resistant tuberculosis (XDR-TB)—alternative medicines are used and the duration of the regimen is also lengthened.

Preexisting HIV infection increases the incidence of and potentiates tuberculosis. Active tubercular disease, in turn, hastens the progress of HIV infection towards full-blown AIDS.

Of course, all HIV patients are not said to be suffering from AIDS or acquired immunodeficiency syndrome. HIV infection progresses in stages, based on the patient’s CD4+ cell count. When CD4+ cell count drops below 200 cells per millilitre of blood, that’s when certain opportunistic infections start occurring.

More opportunistic infections occur at even lower immunity levels, and AIDS-related syndromes set in. Chief among them, HIV-associated wasting syndrome, which is marked by significant involuntary weight loss (10% or more) and muscle mass loss. At this stage, the patient is said to have AIDS. 

In terms of symptoms, HIV patients may remain wholly asymptomatic at first except for some lethargy. Later, with cellular immunity plummeting, characteristic HIV-related opportunistic infections arise.

With the initiation of daily antiretroviral therapy (ART), the prognosis for AIDS patients has drastically improved by effective viral load suppression.

In those patients whose immune system has been weakened by HIV infection, and who are not receiving adequate or any, antiretroviral therapy to suppress the viral load and prevent further diminution of immunity, active tuberculosis infection is common.

While in most immunocompetent patients tuberculosis occurs as a latent asymptomatic infection, in HIV positive individuals the risk of progression to active tubercular disease is 18 times greater. Further, while individuals with strong immunity are only at a 5% to 10% risk of contracting tuberculosis in their lifetimes, an HIV positive person faces the same amount of risk of TB every single year of their lives.

The WHO recommends relying on the following four symptoms to clinically suspect tuberculosis in adults living with HIV:

• Current cough (of any duration)
• Fever (of any duration)
• Weight loss
• Night sweats
  
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And the following four rouse clinical suspicion of tuberculosis in children (more than 12 months of age) living with HIV):

• Poor weight gain
• Fever (of any duration)
• Current cough (of any duration)
• History of contact with a tuberculosis patient

The presence of these four is assessed at each meeting and dictate the further course of action. If none are present, isoniazid prophylaxis therapy (explained ahead) is started, however, if any are present, tuberculosis testing is carried out.

IRIS is a phenomenon by which, with the beginning of recovery of the immune system in immunosuppressed HIV patients, previously acquired opportunistic infections like tuberculosis, which were earlier mild to asymptomatic, flare up and present with exaggerated symptoms. 

Current Indian guidelines state that to prevent treatment failure and for ease of patients, anti-tubercular treatment (ATT) drugs be administered daily as weight-specific fixed dose combinations (FDCs). This means that the four key ATT drugs—rifampicin, isoniazid, pyrazinamide and ethambutol—are formulated as a single tablet to be taken once a day along with daily antiretroviral therapy (ART) drugs. The dose of drugs in FDCs are based on weight-bands.

Tuberculosis treatment for PLHIV (people living with HIV) is the same as that for those without HIV. Drug-sensitive pulmonary tuberculosis is treated with rifampicin, isoniazid, pyrazinamide and ethambutol for the first four months (intensive phase), followed by two months (continuation phase) of rifampicin, isoniazid and ethambutol.

In case the patient is receiving second-line ART with protease inhibitors (like lopinavir/ritonavir), rifampicin should be replaced by rifabutin.

Conversely, if a tuberculosis patient is diagnosed with HIV, antiretroviral therapy (ART) should be initiated only after a minimum of two weeks to a maximum of two months of start of anti-tubercular treatment (ATT). This is because sudden reactivation of the suppressed immune system in a tuberculosis patient could cause immune reconstitution inflammatory syndrome (IRIS).

However, if the CD4+ cell count is 50 or less, ART must be started as soon as possible—that is, on completion of two weeks of ATT. If IRIS is suspected due to sudden worsening of symptoms, first ATT failure is ruled out and then, if the reaction is severe, steroid therapy may be considered by the doctors.

The National AIDS Control Programme (NACP) and National Tuberculosis Elimination Program or NTEP (previously known as the Revised National Tuberculosis Control Program of India) have created a joint framework under which tuberculosis and HIV prevention and management activities are coordinated.

99 DOTS for HIV TB coinfection

To specifically target the high burden of tuberculosis-HIV co-infection due to poor patient compliance, the government launched 99 DOTS in 2015. This novel system was instituted to monitor daily intake of anti-tubercular treatment DOTS (directly observed treatment short-course) by HIV co-infected patients. Special ATT blister-packs are given to patients who can not commute to the ART centre daily. On opening each blister to take the ATT FDC tablet out, a mobile phone number, that can not be guessed by the patient, is revealed. Patients are instructed to leave a missed-call on this toll-free number. These calls register with a centralised system, providing confidence that the ATT was “in hand” and most likely taken. This allows monitoring of adherence to treatment and tracking of missed doses.