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Indian Journal for the Practising Doctor

Spectrum of Tuberculous Infection in People Living With HIV/AIDS in Jammu

Author(s): Rampal, V , Sharma AKL, Saini RK

Vol. 5, No. 5 (2008-11 - 2008-12)

ISSN: 0973-516X

Rampal, V , Sharma AKL, Saini RK

Dr. Vinay Rampal, Dr. A.K. Sharma, Dr. R. K. Saini, PG Department of Medicine, Govt. Medical College, Jammu

Tuberculosis is one of the commonest bacterial infections of mankind in both developed and developing nations. Although it primarily infects the lungs, its extra pulmonary manifestations are not rare. HIV-infection predisposes individuals to tubercular infection in a big way and the risk of developing active tuberculosis increases 50 to 60 fold. Since Myco tuberculosis spreads mainly through droplet infection, the increase in active tuberculosis among dually infected people means more carriers of tuberculosis and this in turn would mean faster transmission of tubercle bacilli in the whole population.

The diagnosis of tuberculosis in HIV +ve cases has a lot of significance, as tuberculosis spreads faster in HIV +ve populations and is also difficult to diagnose in them than in HIV –ve people. Moreover, tuberculosis gets activated earlier in the course of HIV infection and in an unusual way in comparison to many other opportunistic infections in India. Also, tuberculosis in HIV +ve cases is more likely to prove fatal, if left undiagnosed and untreated.

A proper combination of anti-tubercular drugs achieves both prevention and cure of the disease in the HIV positive. Effective treatment quickly makes the individual non- infective and stops further infection. The DOTS strategy treats tuberculosis in HIV +ve persons as effectively as it treats in those without concomitant infection. A complete cure takes 6-8 months. Since, in addition to curing the individual, chemotherapy prevents further transmission of infection so it assumes a lot of public health importance.

Isoniazid preventive therapy is recommended as a preserving measure in HIV +ve persons at the risk of contracting tuberculosis, as well as those with latent tubercular infection

Active tuberculosis, being the commonest opportunistic infection in ‘people living with HIV/AIDS’ (PLWHA) in India and a major cause of mortality and morbidity with emergence of MDR and XDR, has become a formidable challenge. India with 1.8 million cases of tuberculosis occurring annually, the life time risk of developing active tuberculosis is six times more in a person with dual infection. Dual infection shortens the life span and hastens the progress to AIDS. In spite of ATT & ART being made freely available to the majority of patients, the containment of this epidemic has not been quite satisfactory in our country.

Material & Methods

This study was carried out in the attached VCTC and wards of the Government Medical College Hospital, Jammu. Sixty persons 40 males, 20 females) suffering from HIV and tuberculosis were observed for a period of 15 months from April, 2007 to August, 2008.

Chart I: Age-wise manifestations of HIV/Tuberculosis Co-Infection

Out of 60 patients, pulmonary tuberculosis was seen in 46 (76.67%), extra pulmonary in 6 (10%), lymph node TB in 4 (6.67%) , and generalized tuberculosis in another 4 (6.67%). The maximum number of patients, 28 (46%) were in the age group of 35-47 which is the most productive period of life and the majority suffered from pulmonary, followed by extrapulmonary (in the form of ileo-caecal TB, presenting as prolonged diarrhea), 3 suffered tuberculous meningitis and 4 suffered generalised tuberculosis. This was followed by the middle-aged group, 48-60 (18 cases). The maximum number of nodal involvement (3) was seen in the younger age group (22-34) presenting as scrofula, as shown in chart 1.

All the patients were subjected to clinical and biochemical evaluation i.e. Haemogram, ESR, Chest X-Ray, Sputum analysis, ultrasound abdomen, lipid profile and CD4 counts at the beginning and every three months. The CD4+ count at the beginning was 101-200 in 21 patients, 201-500 in 19 patients, over 500 in 1 patient and less than 100 in only 9 patients.

No cotrimoxazole prophylaxis was administered to any of the patients. Different anti-tuberculous regimes were used depending upon the type and presentation of the patient. Forty-six of the patients were put on a combination of Rifampicin + INH + Ethambutol and Pyrizinamide (Regime – I) and 14 on a combination of Streptomycin + Ethambutol + IHN and Pyrizinamide (Regime – II) for the first 6 months with removal of 1 drug each for the rest of 3 months. Thirty patients with CD4+T cell count <200 were started with ART (Anti-Retroviral Therapy), those with CD4+ count <100 were started ART one month after the initiation of ATT (Anti-tTuberculous Therapy).

Observations

Forty patients, all on ATT regimen I (20 on Nevirapine containing ART regime) developed significant rise in SGOT, SGPT and serum alkaline phosphatase without any evidence of jaundice by the 6th-12th week, which continued to rise till the 18th week; there were no other signs of liver cell failure. After the 18th week, there was a decline in the serum enzymes with return towards normal by the 36th week to the 46th week. All patients had normal lipid profile at the beginning but 6 patients showed a gradual rise in serum cholesterol and triglycerides by the 12th week which continued to rise progressively till the 18th week. These patients, in the age group of 48-60 years, showed no clinical abnormality like gall bladder disease or IHD, and continued in a raised state till 28th week, showing a decline thereafter without any pharmacotherapy. By the end of 15th month, their lipid profiles had come to the baseline. However, pancreatitis developed in 4 persons, irrespective of their lipid profile, who were chronic alcoholics and long-route drivers who started early on ATT. Their ATT was withdrawn and they were treated conservatively for 2 weeks to which they responded, and ATT restarted after 4 weeks. However, no mortality occurred. (Table 1)

Table 1: Changing Lipid Profile With Continuing Therapy

Time Period No. of Patients
Till 3 Months Cholesterol <200 60
>200 0
TGL <150 60
>150 0
6 months Cholesterol <200 54
>200 6
TGL <150 54
>150 6
9 months Cholesterol <200 56
>200 4
TGL <150 56
>150 4
12 months Cholesterol <200 58
>200 2
TGL <150 58
>150 2
15 months Cholesterol <200 59
>200 1
TGL <150 59
>150 1

Rest of the patients had slight alterations in their lipid profile but not of much significance. Although viral load estimation was not available, there was a linear response in the rise of CD4+ T-cells with treatment in both AIDS and HIV patients, as shown in Table 2.

Table 2: Relation of CD4+T Cells to response of Therapy

CD4+T Cell
Counts/Cmm
At the start
of therapy
3 months 6 months 9 months 12 months 15 months
500> 11 16 21 34 42 51
201-500 19 21 25 19 15 09
101-200 21 16 10 05 03 0
<100 9 7 4 2 0 0

Immune Reconstitution Inflammatory Syndrome (IRIS), another enigmatic complication of HIV/TB co-infection treatment, which is difficult to distinguish from drug failure/resistance, and many a time has led to institution of second-line anti-tubercular drugs, was also observed in only two patients with CD4 counts less than 100 at the beginning, presenting in the 5th week of initiation of treatment. This complication required admission in the hospital and start of corticosteroids.

One patient developed typical lipodystrophy involving the cheeks and buttocks during the course of this study.

Discussion

One important finding – the onset of dyslipidemias with the start of HAART (Highly Active Anti Retroviral Therapy) – was seen as a considerable rise in cholesterol and triglycerides levels in six patients starting from 6th week, which reached a nadir in 15 weeks. No untoward effects like IHD and gall bladder disease were seen during this period, however, pancreatitis occurred in 4 patients on Stavudine-containing regimens in chronic alcoholic drivers. There was a gradual return to normalcy by 8 – 12 weeks and by the end of 15th months, the lipid profile had reverted to normal. This rules out the stigma of dyslipidaemias associated with HIV/AIDS and HAART.

Another much disturbing fact about co-administration of HAART and ATT reflecting damage to liver seen as a rise in liver enzymes was noted in 40 patients (20 on Nevirapine) from 1st to 12th week. No jaundice or alterations in serum proteins or sign of liver failure was observed in any of the patients; after 16 weeks 4 of the patients were having normal enzymes and the rest had reached normalcy by the 24th week. By 9 months all liver function tests were normal. This rules out the apprehension of enhanced of hepatic injury induced by a combination of ATT and HAART (especially a combination of Nevirapine + Rifampicin)

Since tuberculosis was the commonest opportunistic infection, co-trimaxzole prophylaxis was abandoned without any complications.

Conclusion

Dyslipidemias being one of the commonest complications of HAART (presenting as IHD in 70% cases in the Western literature). This predominantly reported manifestation was not seen in our study. Although, there was an initial rise in the lipids (both cholesterol & triglycerides), this was followed by a return to normal without any pharmacotherapy and any unfavourable cardio-vascular event.

Patients receiving a combination of Nevirapine containing HAART regimen and Rifampicin containing ATT, though notorious in western literature for decreased plasma concentration, increased hepatic injury and Rifampicin toxicity were not observed in this study. Three patients on Nevirapine containing regimen developed severe rash demanding withdrawal of the drug but none of them was receiving Rifampicin.

Although of unknown etiology, Immune Reconstitution Inflammatory Syndrome (IRIS) continues to show its presence in patients of Tuberculosis with reduced CD4+T cells as a re-emergence of the diminished immunity in the individual.

Clinical Implications

ATT and ART being available free in India can be life saving if started simultaneously. ART may be delayed in very sick patients and started after stabilizing the tuberculous disease. Nevirapine and Rifampicin can also be co-administered as no enhanced hepatic toxicity, reduced-response or untoward events were substantiated. Similarly there was no sustained altered lipid profile resulting in heavy cardiac mortality as reported in the studies from West (70% on autopsy). The reasons are not known but may be due to genetic, racial, hereditary, dietary, environmental or some other unknown factors which this ongoing study may reveal in the years to come. Routine cotrimaxozole prophylaxis may only result in unwanted bone marrow depression and renal stones besides hypersensitivity in some cases, and can be considered unwarranted in Indian set-up, where the main opportunistic infection is tuberculosis.

References

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