once believed to be on the verge of extinction in united states , mycobacterium tuberculosis showed a resurgence with the onset of human immunodeficiency virus ( hiv ) epidemic .
hiv - positive persons have a more than 20-fold increased risk of developing tuberculosis ( tb ) as compared to hiv - negative individuals .
hiv infection has contributed significantly to the global increase in the incidence of tb and active tb is one of the most common opportunistic infections ( oi ) in hiv - positive patients in endemic areas of tuberculosis .
india has a significant burden of hiv infection and tb with an estimated 2.5 million people living with hiv and aids ( plwha ) at the end of the year 2007 and an estimated 1.8 million cases of tb are detected every year .
tuberculosis also accounted for approximately 20% of 1.8 million aids - related deaths worldwide in the year 2009 .
active tb is also an independent risk factor increasing the progression of hiv - aids .
the national aids control organization ( naco ) , india , has classified the ois in hiv - positive patients into 12 categories and provided guidelines for their prevention and treatment .
the use of revised national tuberculosis control programme ( rntcp ) guidelines is recommended for treatment of tb in these patients .
however , currently , data regarding efficacy and safety of these drugs in these patients is limited .
hence , the present study was undertaken to evaluate the efficacy and safety of anti - tuberculosis drugs in these patients .
the study was a part of a drug utilization study carried out to evaluate the utilization pattern and safety of drugs used for treatment of ois in outdoor and hospitalized hiv - positive patients .
it was an observational , prospective , single centre study carried out at the anti retroviral therapy ( art ) centre of a tertiary care hospital in ahmedabad , for a period of 21 months from september 2010 to june 2012 .
the approval to conduct the study was obtained from the nodal officer , art centre , gujarat state aids control society ( gsacs ) and the institutional ethics committee ( ref no .
all hiv - positive patients reporting to the centre were screened for the presence of ois .
patients ( either art naive or those receiving art ) , registered with the parent art centre at civil hospital , who were newly diagnosed to be suffering from oi were included in the study after a written informed consent . a purposive sampling of the study population was carried out based on the previous data about the prevalence of different ois in these patients .
patients were enrolled during the first nine months of study period and followed up for a period of one year to monitor any new or recurrent oi .
demographic characteristics ( age and gender ) , mode of hiv transmission and details of ois ( clinical features , laboratory investigations , and outcome ) were noted .
details of drugs used in the treatment of ois and adverse reactions due to these drugs were also recorded .
the data obtained from patients suffering from tuberculosis were analyzed for demographic and other characteristics , mode of hiv transmission , type of tuberculosis , baseline cd4 count , efficacy , safety , and adherence to naco guidelines .
adrs were evaluated for severity using modified hartwig and seigel scale and a causality assessment was done using the who - umc criteria and naranjo 's scale .
fischer 's exact test was used to assess the gender differences in mortality rate due to tb .
a total of 222 ois were observed in 134 enrolled patients . tuberculosis ( tb ) was the most common oi detected in 89 ( 66.4% ) patients [ figure 1 ] .
of the 89 patients , 79 were adults ( 54 males and 25 females ) with a mean age of 39.05  11.7 years and a mean baseline cd4 count of 144.53  93.78 cells / microliter .
the cd4 count was less than 500 cells/ microliter in all adults [ table 1 ] .
the mean age and baseline cd4 count of 10 children ( five males and five females ) was 9.4  3.63 years and 726.5  649.80 cells / microliter , respectively .
the modes of hiv transmission among adult patients were heterosexual ( 50 patients ) and blood transfusion ( 14 patients ) .
the modes of hiv transmission among pediatric patients were vertical ( 7 patients ) and blood transfusion ( one patient ) , while the mode of transmission was unknown in two children .
opportunistic infections ( ois ) observed in hiv positive patients ( n = 134 ) in a tertiary care hospital outcome in hiv - positive patients suffering from tuberculosis different manifestations of tb included abdominal tb ( n = 55 , 61.7% ) , pulmonary tb ( n = 18 , 20.2% ) , combined form of pulmonary and extra pulmonary tb ( n = 6 , 6.7% ) , pleural effusion ( n = 5 , 5.6% ) , lymphadenitis ( cervical ) ( n = 3 , 3.3% ) and meningitis ( n = 2 , 2.2% ) [ figure 2 ] .
manifestations of tuberculosis in hiv positive patients at a tertiary care hospital ( n = 89 ) anti - tuberculosis drugs were prescribed to these patients according to the rntcp guidelines as recommended by naco .
accordingly , patients suffering from tb for the first time ( n = 65 ) received category i drugs ( isoniazid , rifampicin , pyrazinamide , and ethambutol in the usual recommended doses ) , while patients having relapse or failure of treatment and the defaulters ( n = 23 ) were prescribed category ii drugs ( isoniazid , rifampicin , pyrazinamide , ethambutol , and streptomycin in the usual recommended doses ) .
one patient preferred to receive treatment from a private practitioner because of less pill burden due to prescription of fixed drug combinations . noncompliance was observed in one case , where patient defaulted category i treatment and was later switched to category ii treatment .
of the 89 patients , outcome was not assessable in 19 cases since these patients were either lost to follow up , transferred out , or the treatment was continuing at the end of study period . of the remaining 70 patients , 58 ( 82.8% )
mortality was more in females ( n = 7 , 31.8% ) as compared to males ( n = 5 , 12.8% ) ( p = 0.0978 ) .
the mean baseline cd4 count , drug treatment and outcome in these patients are mentioned in table 1 .
of the 55 cases of abdominal tb , 49 were observed in adults and six in children . among them , one patient attended a private clinic and was prescribed forcox ( fixed drug combination of isoniazid , rifampicin , pyrazinamide and ethambutol ) and akt-3 ( fixed drug combination of isoniazid , rifampicin and ethambutol ) .
abdominal tb was associated with six of the total 12 deaths observed [ table 1 ] . of the total 18 cases of pulmonary tb observed in adults , eight were sputum positive for acid fast
bacilli ( afb ) , five were sputum negative and in five cases , sputum examination reports were not available .
of the eight cases of sputum positive pulmonary tb , outcome was assessable in seven cases ; five recovered and two died .
of the five sputum negative pulmonary tb cases , outcome was assessable in two cases and both patients were cured . in the remaining five cases where report of sputum examination was not available , outcome was assessable in three . of these , one patient recovered while two patients died .
it was observed that the mean cd4 count of patients suffering from pulmonary tb was lower as compared to those suffering from extrapulmonary tb .
patients with sputum negative pulmonary tb had lower mean cd4 count as compared to sputum positive pulmonary tb [ table 1 ] .
of the five cases of tuberculous pleural effusion , four were detected in adults and one in a 14-year - old child .
outcome was assessable in four cases , of which three were cured and one patient died .
tuberculous meningitis was observed in two patients ( one adult and one child ) , both of whom were cured with the prescribed treatment .
of the three cases of tb lymphadenitis ( cervical ) , two were observed in adults and one in a six year old child . of these , two patients were cured while one patient died .
nevirapine was substituted with efavirenz in ten patients on nevirapine based regime developing tb due to the risk of interaction between nevirapine and rifampicin .
the most common adr was discoloration of urine associated with rifampicin ( 58 cases ) .
majority of adrs ( n = 147 , 98.6% ) were mild in nature with a severity of level 1 as per the modified hartwig and siegel scale .
two severe adrs were detected ( severity level 2 and 3 in one case each ) .
the drug was stopped , patient was treated symptomatically , and the adr subsided thereafter .
iu / l ) was observed in one patient , which required withdrawal of isoniazid and rifampicin .
adverse drug reactions to anti - tuberculosis drugs in hiv - positive patients ( n=89 ) the causality of adrs as assessed by who - umc scale showed that the suspected drug had a possible causal association in 90 cases , probable association in 58 cases , while the drug was the certain cause of adr in one case .
as per the naranjo score , the causality of adr was possible in 90 cases and probable in 59 cases .
tuberculosis was the commonest oi in the present study , in accordance with the fact that in endemic zones , tb is one of the most frequent ois in hiv - positive patients .
a study carried out in pune , india showed that tb was the most common diagnosis ( 55% ) among hospitalized hiv - positive patients .
it is important to assess the efficacy and safety of anti - tuberculosis therapy as tb is one of the most common oi in these patients .
hence , the present study was conducted to evaluate the efficacy and safety of anti - tuberculosis drugs in hiv - positive patients . in our study , majority of the cases were observed in adults .
this might be attributed to higher mean baseline cd4 count observed in pediatric patients as compared to adults and hence an overall lesser risk of ois .
art restores the immune response of the patient and protects the patient from the risk of ois and accordingly , tb was less common in hiv - positive patients receiving art . a study conducted in south india also showed that the incidence of ois among hiv - positive patients receiving haart was much lower than that in patients not receiving haart .
art was initiated in majority of art naive patients subsequently and it was prescribed in accordance with the naco guidelines .
decreased mortality has been observed in hiv - tb co - infected patients receiving art as compared to those who do not receive art and early initiation of art in hiv tb co - infected patients helps reduce the mortality . in the present study , extra - pulmonary tb ( 73% ) was more common than pulmonary tb ( 20.2% ) in contrast to another study .
similarly , the mean baseline cd4 count of patients suffering from pulmonary tb was lower than that of patients of extra - pulmonary tb which is contrary to the available literature and needs further evaluation .
the mean cd4 count of patients suffering from sputum negative pulmonary tb was lower than that of sputum positive cases , in accordance with the fact that sputum negative tb is more common in patients with advanced immunosuppression .
all patients were treated in accordance with rntcp guidelines as recommended by naco . under the rntcp programme ,
patients are dispensed akt during the intensive phase in a blister pack containing multiple drugs per pack to be taken thrice a week .
this can significantly increase the pill burden in these patients who also receive art and other medications like cotrimoxazole for prophylaxis of pcp , nutritional supplements etc .
increased pill burden is known to affect the compliance adversely and may lead to the development of drug resistance in both hiv infection and tb . however , in spite of increased pill burden , non - compliance to akt was uncommon in the present study . yet , inclusion of fdcs in treatment of tb can help reduce the pill burden and improve compliance to therapy .
treatment outcome was not assessable in nearly 21% patients due to a variety of reasons . in the remaining
, treatment was curative in nearly 82.8% of patients . mortality rate ( 17.1% ) in these patients was comparable to that reported globally due to tb in aids patients ( 12% in the year 2000 and 20% in the year 2009 ) indicating that the rntcp regimes are effective in treating tb in these patients .
these figures are higher than the mortality rate reported in hiv negative patients suffering from tb ( 0.024% ) in india in 2011
. multiple factors such as presence of concomitant diseases , poor general health in hiv positive patients and non - initiation of art are associated with increased mortality in these patients .
gender differences in mortality observed in our study could not be explained based from the available data and further studies are required to substantiate or negate this finding .
nevirapine was substituted with efavirenz in all patients receiving nevirapine based art to avoid the potential interaction between rifampicin and nevirapine .
rifampicin induces the metabolism of nevirapine , leading to a reduction in the plasma level of nevirapine , although some studies have shown that it does not significantly affect the antiviral effect of nevirapine .
have also observed that the dose modification of nevirapine is not required in patients receiving both nevirapine and rifampicin , and there is no significant change in plasma level of rifampicin in these patients .
the risk of combined toxicities like liver damage or skin rash is also not significantly increased in patients receiving both nevirapine and rifampicin .
hence , consequences of co administration of nevirapine and rifampicin need to be further evaluated to help simplify the choice of art regime in these patients .
the number of adrs associated with anti - tuberculosis drugs per patient in this study was higher than the reported incidence worldwide .
this can be attributed to multi - drug therapy , coexisting hiv infection and prolonged treatment .
majority of adrs were non - serious in nature and did not warrant a change in treatment , suggesting that the drugs were well tolerated .
gastrointestinal adrs were also frequent , which is explained by the fact that most of these drugs were administered by oral route .
dermatological adrs , more frequent in hiv - positive patients , were , however , less common in the present study and majority of these were non - serious . as these patients were also receiving concomitant drugs like art , cotrimoxazole , and nutritional supplements , a 
the study was conducted at the art center of a tertiary care hospital for 21 months .
it was prospective in nature and all patients visiting the center were enrolled according to the selection criteria and followed up regularly .
majority of the studies previously conducted in india have focussed on the pattern of oi in hospitalized hiv positive patients , while the present study included both indoor and outdoor patients .
the long duration of follow up ( one year ) allowed us to assess the recurrence and outcome in these patients .
the pattern of tb and the efficacy and safety of anti - tuberculosis drugs in pediatric patients could not be assessed adequately because of the small number of patients enrolled .
hence , the possibility of recall bias in adr reporting could not be ruled out .
the number of adrs associated with anti - tuberculosis drugs per patient in this study was higher than the reported incidence worldwide .
this can be attributed to multi - drug therapy , coexisting hiv infection and prolonged treatment .
majority of adrs were non - serious in nature and did not warrant a change in treatment , suggesting that the drugs were well tolerated .
gastrointestinal adrs were also frequent , which is explained by the fact that most of these drugs were administered by oral route .
dermatological adrs , more frequent in hiv - positive patients , were , however , less common in the present study and majority of these were non - serious . as these patients were also receiving concomitant drugs like art , cotrimoxazole , and nutritional supplements , a 
the study was conducted at the art center of a tertiary care hospital for 21 months .
it was prospective in nature and all patients visiting the center were enrolled according to the selection criteria and followed up regularly .
majority of the studies previously conducted in india have focussed on the pattern of oi in hospitalized hiv positive patients , while the present study included both indoor and outdoor patients .
the long duration of follow up ( one year ) allowed us to assess the recurrence and outcome in these patients .
the pattern of tb and the efficacy and safety of anti - tuberculosis drugs in pediatric patients could not be assessed adequately because of the small number of patients enrolled .
hence , the possibility of recall bias in adr reporting could not be ruled out .
tuberculosis ( tb ) is the most common opportunistic infection ( oi ) in hiv - positive patients with a preponderance of extrapulmonary over pulmonary tb . a rational approach in prescribing the medication is observed .
anti - tuberculosis drugs are effective in majority of the patients and are well tolerated with only a few serious adrs .
further studies are recommended to determine the pattern of tb in hiv - positive children , the relation between cd4 count and the type of tb in adults and to determine the consequences of co - administration of nevirapine and rifampicin in these patients .
 objectives : to assess the efficacy and safety of anti - tuberculosis drugs in hiv - positive patients at a tertiary care teaching hospital.materials and methods : as a part of an ongoing study of opportunistic infections ( ois ) in hiv - positive patients , drug treatment in patients suffering from tuberculosis was assessed to determine its efficacy and safety . based on prevalence data for last three years 
 , a purposive sampling of study population was carried out in this observational , prospective , single centre study . 
 tuberculosis ( tb ) was the most common oi observed . 
 the selected patients were followed up for a period of one year to evaluate the clinical course and outcome of ois , and the efficacy and safety of drugs used was checked.results:tuberculosis was observed in 89 out of 134 enrolled patients . 
 these included 79 adults and 10 children . 
 males ( 66.2% ) were commonly affected . 
 extra pulmonary tb ( 73% ) was the most common manifestation with abdominal tb observed in 55 ( 61.7% ) patients . 
 all patients were treated in accordance with the revised national tuberculosis control programme ( rntcp ) guidelines as recommended by national aids control organization ( naco ) , india . 
 outcome of tb was assessable in 70 patients . 
 majority ( 82.8% ) of the patients were cured , while 12 patients ( 17.1% ) died during the course of treatment . 
 a total of 149 adrs were observed in 67 ( 75.2% ) patients . 
 majority of adrs ( n = 147 ) were non - serious and did not warrant a change in therapy . 
 discoloration of urine was the most common adr observed.conclusion:tb is the most common opportunistic infection in hiv - positive patients with abdominal tb being the most common manifestation . 
 rntcp and naco guidelines are adhered to in these patients . 
 anti - tuberculosis drugs are well tolerated and effective in majority of the patients . 
Introduction
Materials and Methods
Results
Discussion
Adverse Drug Reactions
Strengths of the Study
Limitations of the Study
Conclusion