A study of utilization pattern , efficacy and safety of drugs prescribed for opportunistic infections in Human Immunodeficiency Virus infected patients

Objectives: The aim was to evaluate the utilization pattern, effi cacy and safety of drugs prescribed for opportunistic infections (OIs) in human immunodefi ciency virus (HIV) positive patients. Materials and Methods: In this observational, prospective, single center study, HIV positive patients were followed-up for a period of 1 year to record the OIs; their clinical course and outcome. Utilization pattern, effi cacy and safety of the drugs used were evaluated. Rationality of treatment was assessed using National AIDS Control Organization and Standard Treatment Guidelines. Results: A total of 222 OIs were detected in 134 patients. Majority of patients (90.2%) were adults. The commonest OIs included tuberculosis (TB) (89), oropharyngeal candidiasis (OPC) (37), bacterial infections (30) and chronic diarrhea (22). Use of supportive drugs and empirical treatment of certain OIs contributed to a higher number of drugs (average of 3.5 drugs) per prescription. Drugs, prescribed in accordance with the above mentioned guidelines, were effective in most cases. Drugs were well-tolerated with only two serious adverse drug reactions (ADRs) reported. Majority of ADRs were associated with anti TB drugs. Conclusion: Tuberculosis, oropharyngeal candidiasis, bacterial infections and chronic diarrhea are the commonest OIs. Overall, a rational approach to therapy and good tolerability and effi cacy of drugs was observed. Empirical treatment of infections should be minimized.


INTRODUCTION
Acquired immunodefi ciency syndrome (AIDS) is defi ned as the occurrence of life-threatening opportunistic infections (OIs), malignancies, neurological diseases and other specifi c illnesses in patients with human immunodefi ciency virus (HIV) infection and CD4 counts <200 cells/mm 3 . [1]early, 2.27 million people in India are infected with HIV and the prevalence rate in adults is 0.31% in India. [2]OIs are a chief cause of AIDS related mortality [3] and timely intervention helps to increase longevity and to prevent transmission of these infections in the community. [2]e National AIDS Control Organization (NACO), India classifi es OIs into 12 categories and has provided guidelines for their prevention and treatment.These include tuberculosis (TB), oral candidiasis, chronic diarrhea, herpes zoster (HZ), other herpes virus infections, bacterial infections, cytomegalovirus (CMV) retinitis, Pneumocystis jiroveci pneumonia, cryptococcal meningitis, toxoplasmosis, mycobacterium avium complex infection and other OIs.The guidelines recommend the use of specifi c antimicrobials [Appendices 1 and 2] and other drugs (e.g.glucocorticoids, analgesics, antidiarrheal drugs etc.). [1]owever, data regarding utilization, effi cacy and safety of these drugs is sparse.This study aimed to evaluate the utilization pattern, effi cacy and safety of drugs used in OIs in HIV positive patients.The investigator attended the outpatient department of ART Center daily.Patients newly diagnosed to be suffering from OI, who were willing to provide a voluntary written informed consent and report for regular follow-up were included.A purposive sampling of the study population was carried out based on the available data of prevalence of different OIs in these patients.Patients were enrolled during the fi rst 9 months of study period and monitored for 1 year for new or recurrent OI.Demographic characteristics (age and gender), mode of HIV transmission, total number and types of OIs, their clinical course and outcome were noted in a pretested case record form.Details of drugs prescribed for treatment of OIs and the associated adverse drug reactions (ADRs) were recorded.Outcome of treatment was assessed by the treating physician and recorded by the investigator.ADRs were evaluated for severity using the modifi ed Hartwig   Siegel scale. [4]The Central Drugs Standard Control Organization's criteria [5] for monitoring the progression of ADRs and WHO UMC causality scale and Naranjo's score for causality assessment of ADRs were used.Rationality of treatment was assessed based on the adherence to the NACO [1] and other recommended guidelines. [6]  through blood transfusion (15.7%), while that among children was predominantly vertical (69.2%) [Figure 1].Mean age of adult and pediatric patients were 39.6 ± 11.59 years and 9.3 ± 3.22 years respectively [Figure 2].Mean baseline CD4 count of adults and pediatric patients were 178.84 ± 147.26 cells/μl and 642.3 ± 585.55 cells/μl respectively (P < 0.0001).

Utilization pattern of drugs
A total of 763 drugs were prescribed in 217 cases (an average of 3.5 drugs/case).Of these, 688 (90.1%) were prescribed orally, 65 (8.5%) parenterally and 10 (1.3%) by topical route.A total of 580 (76%) antimicrobials were prescribed.Prescribing by generic and brand names was 566 (74.1%) and 197 (25.8%) respectively.A total of 705 (92.3%) drugs were prescribed from hospital pharmacy, whereas 58 (7.6%) were prescribed from the private pharmacies.Of 763 drugs, 678 (88.8%) were included in WHO Essential Medicine List 2011.Treatment details of fi ve cases, where patients received treatment from private practitioners, were not available.

Opportunistic infections
A total of 222 OIs were observed including TB, oropharyngeal candidiasis (OPC), bacterial infections, chronic diarrhea, acute diarrhea, herpes zoster (HZ), CMV infections, herpes simplex, P. jiroveci pneumonia, cryptococcal meningitis and toxoplasmosis.More than one OI was suspected in four cases [Figure 3].Outcome of OI was not assessable in 29 cases, since the patients were either Details of two patients suff ering from pneumonia were not available.*Formulations prescribed to pediatric patients

Oropharyngeal candidiasis
A total of 37 cases (26 in men and 11 in women) of OPC were observed in adults with a mean baseline CD4 count of 98.08 ± 80.79 cells/μl.Of these, 24 were observed in ART naive patients.All patients received oral fl uconazole therapy as recommended by NACO.In addition, intravenous fl uconazole was prescribed in one case and topical clotrimazole in two cases.Outcome was assessable in 32 cases, all of whom were cured.A single episode of recurrence was observed in seven patients.In three adults, both OPC and herpes simplex infection were suspected.It was cured with a combination of acyclovir and fl uconazole.
Bacterial skin infections (boils and otitis externa) were cured with recommended doses of oral antibacterial drugs (co-amoxiclav and amoxicillin respectively), topical antibacterial drugs (polymyxin B lost to follow-up or since treatment was continuing at the end of study period.

Tuberculosis
The results of effi cacy and safety of anti TB drugs in HIV positive patients have been published by the authors. [7]Tuberculosis was observed in 89 patients.Abdominal TB, pulmonary

Acute diarrhea
Nineteen cases of acute diarrhea were observed in adults (15 in men and four in women; mean CD4 count of 284.05 ± 271.72 cells/μl).Abdominal TB was observed in fi ve patients, while four patients had suffered from chronic diarrhea earlier.Both abdominal TB and a history of chronic diarrhea were present in two patients.A total of 48 drugs were prescribed in 18 cases (an average of 2.66 drugs per case) [Table 3].Treatment details of one patient were not available.Mean duration of antimicrobial use in these patients was 7.72 ± 3.32 days.Switching between different fl uoroquinolones, that is, ciprofl oxacin, norfl oxacin and ofl oxacin was observed in one patient.All except one were cured.

Herpes zoster
Nine cases of HZ (eight adults and one child) were observed.Mean baseline CD4 count of adults was 220.71 ± 102.56 cells/μl.Herpes zoster occurred within 3 and 6 months of initiation of ART in three cases each and within 12 months of initiation of ART in one.Patients were prescribed acyclovir in accordance with the NACO guidelines. [1]ther drugs, that is, nonsteroidal antiinfl ammatory drugs (NSAIDs), antihistaminics, calamine lotion and gabapentin-mecobalamin combination were used in usual recommended doses.Two patients were also prescribed topical and/or systemic antibacterial drugs (framycetin, neomycin and ciprofl oxacin).Treatment details of one patient were not available.Six patients, in whom outcome was assessable, were cured.

Herpes simplex
Herpes simplex labialis was observed in two adults (mean CD4 count of 111.5 ± 75.66 cells/μl), one of whom was ART naive.Patients received oral acyclovir in the usual recommended doses and were cured.

Cytomegalovirus retinitis
Cytomegalovirus retinitis was observed in fi ve adults (mean baseline CD4 count of 138.8 ± 165.44 cells/μl) CD4 count was <50 cells/ μl in three cases.One patient, suffering from Burkitt's lymphoma, had a baseline CD4 count of 341 cells/μl.Four patients received oral valganciclovir in accordance with the NACO guidelines. [1]rogressive visual loss was arrested in these cases.Outcome was not assessable in one patient.

Cytomegalovirus esophagitis
Cytomegalovirus esophagitis was observed in a 16-year-old ART naive male with a baseline CD4 count of 112 cells/μl.Patient was cured with oral valganciclovir prescribed in usual recommended doses.

Other opportunistic infections
Pneumocystis jiroveci pneumonia was observed in two ART naive adult males.Patients were treated with combination antimicrobial therapy, corticosteroids, furosemide, paracetamol and expectorants in the usual doses.Cotrimoxazole was used in the doses of 3.84 and 5.76 g/day in one case each for a mean duration of 11.0 ± 5.66 days.One of the patients died during treatment.Cryptococcal meningitis, observed in a patient who was also receiving category II anti TB drugs for TB meningitis, was cured with intravenous amphotericin B, fl uconazole and supportive drugs used for 15 days as recommended.Toxoplasmosis was observed in one patient, who was also suffering from sputum positive pulmonary TB and had a recent history of chronic diarrhea.Pyrimethamine, clindamycin, cefotaxime, cefoperazone-sulbactam, fl uconazole and aspirin were prescribed in the usual recommended doses, but the patient succumbed to the infection.

Antiretroviral therapy and changes in antiretroviral therapy due to opportunistic infections
Of 134 patients, 103 were ART naive at enrollment.ART was initiated as per the NACO guidelines in majority of naive patients.Boosted protease inhibitor (PI) (lopinavir/ritonavir) were prescribed to one patient developing failure of fi rst line ART.Nevirapine was substituted with efavirenz in ten patients with TB due to a potential of interaction between nevirapine and rifampicin.Efavirenz was substituted with nevirapine after completion of anti TB treatment in 47 patients.

Adverse drug reactions
A total 165 ADRs were observed [

DISCUSSION
Opportunistic infections are one of the important causes of mortality in AIDS. [2]The National AIDS Control Organization, India has recommended guidelines for prevention and treatment of these infections. [1]However, data regarding effi cacy and safety of drugs used to treat OIs is limited.This study was therefore conducted to evaluate the utilization pattern, effi cacy and safety of these drugs.
A total of 222 OIs were observed.Most common OI observed was Tuberculosis, followed by oropharyngeal candidiasis, bacterial infections, chronic diarrhea, acute diarrhea and herpes zoster.Less common OIs included herpes simplex, P. jiroveci pneumonia, cryptococcal meningitis and toxoplasmosis.Our fi ndings differ from those of a study carried out in Kolkata, India, in which oral candidiasis, chronic diarrhea and herpes simplex virus (HSV)-2 infections were the commonest OIs followed by TB and CMV infections. [2]Further studies are recommended to determine the reasons for these variations.
Opportunistic infections were more frequent in middle aged males in our study.A study of hospitalized HIV positive patients carried out at Pune, India also showed that male patients with a mean age of 35.2 years were commonly affected. [8]OIs in these young patients affect work output and increase the overall health expenditure.The mean baseline CD4 count of children was signifi cantly higher when compared to adults and OIs were less common in children.This can be attributed to a progressive loss of lymphoid tissue [9] and deterioration of T-cell function with increasing age.
Antimicrobials were most frequently prescribed drugs.A number of concomitant medications such as pyridoxine, NSAIDs, antihistaminics, glucocorticoids, ORS, intravenous fluids, lactobacillus sporogenes, racecadotril, bronchodilators etc., were also prescribed.Nearly 66% patients were prescribed antitubercular drugs.This increased the number of drugs per prescription.While this treatment was rational and as per the NACO guidelines, the number of drugs per prescription was also high in cases of acute and chronic diarrhea due to empirical treatment.A routine stool examination of HIV positive patients suffering from diarrhea is therefore recommended to optimize drug therapy.Empirical treatment was also employed in pyogenic meningitis, pneumocystis jirovcei pneumonia and toxoplasmosis, which could have been avoided.
Majority drugs were prescribed orally and by their generic names, except certain antimicrobials.Parenteral therapy was required only in serious infections such as PCP, meningitis and severe diarrhea.
Overall, a rational approach in the selection of drugs and their formulations was observed.Most drugs were dispensed free of cost from the hospital pharmacy, which is important to ensure adherence to treatment in these patients and reduces the treatment burden of the patients.The choice of drugs was in concurrence with the NACO guidelines and WHO Essential Medicine List 2011.
Tuberculosis was the most common OI observed with extra pulmonary and abdominal TB being more frequent.All patients were treated as recommended by NACO and majority were cured.Tuberculosis was the most common cause of death in our study as has been suggested by other researchers too. [10]The three I's for HIV-TB as recommended by WHO, that is, intensifi ed TB case fi nding, isoniazid preventive therapy and infection control for TB, [11] is recommended in these patients.
Oropharyngeal candidiasis was the second most common OI observed.Oral thrush commonly occurs and recurs in patients with CD4 cells <200/μl, [12] which was also observed in this study.Oral fl uconazole, prescribed in accordance with the NACO guidelines in all cases, was curative.However, few patients received a combination therapy of oral fl uconazole with parenteral fl uconazole and/or topical clotrimazole, which unnecessarily exposed patients to more drugs and increased the cost of therapy.
Bacterial infections were the third most common OI observed.URTI was commonest followed by LRTI.Bacterial skin infections, UTI and pyogenic meningitis were less common.Bacterial URTI was treated with the recommended drugs in the usual recommended doses and were cured.Antihistaminics, frequently prescribed to these patients, are primarily indicated in viral rhinitis but not in bacterial URTI. [6]ther drugs were also used in recommended doses.Most LRTIs in the present study were less severe and were managed on outpatient basis.Irrational prescribing has been observed for respiratory tract infections, [13] however, it was less common in our study.
Although genitourinary infections are frequent in HIV positive patients, [14] UTI was not a common infection in the present study.Fluoroquinolones were used to treat these infections in the present study.However, use of fluoroquinolones is restricted for the treatment of complicated UTI and not for the regular treatment of uncomplicated cases. [15]Use of multiple formulations and multiple drugs for bacterial skin infections could have been optimized.
Pyogenic meningitis was treated with multiple antimicrobials.The choice of initial empirical therapy depends on patient's age and health status. [16]In patients with suspected impaired cell mediated immunity, a combination of third generation cephalosporin and ampicillin is recommended as initial empirical therapy. [16]Patient in the present study received initial empirical therapy with ceftriaxone.Furthermore, this patient received chloroquine as a part of initial treatment for suspected cerebral malaria and metronidazole for suspected gram negative anaerobic infection.Inappropriate antimicrobial use increases the risk of drug resistance.The choice of initial empirical therapy needs to be reviewed in such cases.Diarrhea was the fourth common OI observed.As chronic diarrhea can be caused by multiple organisms, stool examination helps a defi nitive diagnosis. [1]Stool examination, however, was not performed in these cases and majority patients received a combination antimicrobial therapy.Diarrhea of parasitic origin is more frequent in AIDS patients in developing countries [17] and accordingly, nitazoxanide was frequently prescribed to these patients.However, the role of nitazoxanide in the management of cryptosporidial diarrhea is not clear. [14]Ciprofloxacin and metronidazole were also commonly co-prescribed in the absence of defi nitive diagnosis and hence considered irrational.Lactobacillus sporogenes and racedotril, an intestinal enkephalinase inhibitor used in secretory diarrhea were frequently prescribed.However, effi cacy of L. sporogenes as a probiotic [18] and that of racecadotril for treatment of watery diarrhea in adults [19] is questionable.Loperamide or codeine phosphate, recommended by NACO as antidiarrheal agents in cases of cryptosporidiosis, [1] were not prescribed to these patients.Many patients of diarrhea were later detected to be suffering from underlying abdominal TB.An ultrasonographic examination is therefore recommended for early detection and treatment of this infection.Majority patients of acute diarrhea were also treated empirically with multiple antimicrobials.
Herpes zoster (HZ) was more common in adults receiving ART.Majority of these patients (85.7%) developed HZ within 6 months of initiation of ART, which may be a manifestation of immune reconstitution due to initiation of ART. [1]These patients received oral acyclovir in accordance with NACO guidelines [1] and were cured.Analgesics, antihistaminics and calamine lotion were used to treat associated symptoms as recommended. [6]Use of topical and/or systemic antibacterial agents in a few cases, however, was questionable.Herpes Simplex Virus infection was not frequent in the study population.These patients also received oral acyclovir in accordance with the NACO guidelines [1] and were cured.A few patients presenting with mixed clinical features of both OPC and HSV infection were treated empirically with usual doses of fl uconazole and acyclovir and were cured.
The most common manifestation of CMV infection was CMV retinitis, a fi nding also supported by Jabs. [20]Cytomegalovirus causes end organ disease typically in patients with CD4 cells <50/μl.In a study investigating the prevalence and management of CMV retinitis in China, the mean baseline CD4 count of 23 AIDS patients suffering from CMV retinitis was 31.7 ± 38.6 cells/μl. [21]In this study, however, patients of CMV retinitis had a mean baseline CD4 count of 138.8 ± 165.44 cells/μl.Furthermore, of the six patients suffering from CMV infection, only three had a baseline CD4 count <50 cells/μl.The small sample size could explain this discrepancy.Nonetheless, further studies are recommended to determine the co relation between CMV infections and the CD4 count in these patients.CMV infections were treated with oral valganciclovir in accordance with the NACO guidelines. [1]CMV esophagitis was cured and the progression of CMV retinitis was arrested.Treatment with oral valganciclovir improves the patient compliance and reduces the risk of intravenous therapy associated with ganciclovir. [22]As visual loss is irreversible in cases of CMV retinitis, [1] early detection of the condition with the help of routine fundus examination in patients with CD4 cells <50/μl is recommended. [23]eumocystis jiroveci pneumonia was observed in two patients.Incidence of this infection has declined due to availability of antimicrobial prophylaxis and introduction of highly active antiretroviral therapy. [24]Patients were treated with cotrimoxazole and other drugs in accordance with NACO guidelines. [1]One of the patients died during treatment.Since an increasing prevalence of mutant pneumocystis isolates who show resistance to sulfa drugs has been reported, [25] drug sensitivity test of pulmonary isolates may be recommended in these patients.
Cryptococcal meningitis was observed in one patient, who also had concomitant TB meningitis.Patient was cured with amphotericin B and fl uconazole prescribed in accordance with the NACO guidelines [1] and other supportive medications in usual recommended doses.
Toxoplasma infection was also rare.Patient was treated with pyrimethamine-clindamycin combination therapy as recommended by NACO. [1]Multiple antimicrobials were used initially for empirical treatment.Patient died during treatment, however, this patient was also suffering from pulmonary TB and had a history of chronic diarrhea, which might have contributed to the mortality.

Antiretroviral therapy
Majority of patients (76.8%) suffering from OI were ART naive at the time of enrollment.ART restores the immune response of the patient and protects the patients from the risk of OIs.Accordingly, OIs were less common in patients receiving ART.ART was initiated in majority of naive patients in accordance with the NACO guidelines.
Under the National AIDS Control Program, India, Protease inhibitors are prescribed only to HIV positive patients developing clinical, immunological or virological failure in spite of receiving fi rst line ART drugs for at least 6 months.Protease inhibitors have been documented to exert a protective effect against the risk of toxoplasmic encephalitis [26] and OPC, [27] and benefi cial effects in cases of chronic diarrhea. [28,29]Use of PIs is also associated with signifi cant improvement in survival rates of patients suffering from CMV retinitis. [30]However, only one patient in the study group, who developed immunological failure in spite of receiving fi rst line ART drugs, was prescribed PIs.Inclusion of PIs like lopinavir/ritonavir, atazanavir etc. in the fi rst line ART regimes for patients suffering from the above mentioned OIs may be considered.

Changes in antiretroviral therapy due to opportunistic infections
Nevirapine was substituted with efavirenz in all patients who developed TB, to avoid the risk of interaction between rifampicin and nevirapine as recommended in the guidelines. [1]However, some studies have indicated no signifi cant alterations of plasma rifampicin or nevirapine level in patients receiving both drugs. [31,32]verse drug reactions A total of 165 ADRs were observed.In spite of the fact that these patients were receiving multiple drugs, ADRs were less common indicating that these drugs are well tolerated.Gastrointestinal ADRs were most frequent, which could be attributed to the fact that majority of drugs were prescribed orally.Dermatological ADRs, which are more frequent in HIV positive patients, [18] were not frequent in the present study.Majority of ADRs were nonserious and withdrawal of suspect drug was required only in two cases.Prescription of drugs in accordance with the treatment guidelines might have accounted for their tolerability and safety.

LIMITATIONS OF THE STUDY
The sample size was not adequate to evaluate rarer OIs.However, in spite of these limitations, the fi ndings of the study are valuable vis-avis OI in HIV positive patients in the Indian context, with particular reference to the implementation and effi cacy of recommended treatment guidelines.
Journal of Medicine and Public Health | Jul-Sep 2014 | Vol 4 | Issue 3 State AIDS Control Society and the Institutional Ethics Committee (EC) (Ref No. EC/A/93/10/25.10.10).

*
India.Ministry of Health and Family Welfare.National AIDS control organization.Guidelines for Prevention and Management of Common Opportunistic Infections/ Malignancies among HIV-Infected Adult and Adolescent.May 2007.**Tripathi KD.Antitubercular drugs.In: Tripathi KD, editor.Essentials of Medical Pharmacology.7 th edition.New Delhi: Jaypee Brothers Medical Publishers (P) Ltd., 2013; p. 765-79.NACO = National AIDS Control Organization, DOTS = Directly observed treatment, short-course, HSV = Herpes simplex virus, RNTCP = Revised national tuberculosis control programme, CMV = Cyto-megalovirus, AMB = Amphotericin B, HAART = Highly active antiretroviral therapy, P. jirovecii = Pneumocystis jirovecii, 5-FU = 5-fl uorouracil Ivermectin 12 mg daily for 3 days or Albendazole 400 mg BD for 5 days Maintenance therapy: (to supress symptomatic infection) Albendazole 400 mg or Ivermectin 6 mg once a month ** India.Ministry of Health & Family Welfare.National AIDS control organization.Guidelines for Prevention and Management of Common Opportunistic Infections/ Malignancies among HIV-Infected Adult and Adolescent.May 2007.NACO = National AIDS Control Organization, IV = intravenous

Figure 1 :
Figure 1: Mode of transmission in HIV positive patients (n = 134) with opportunistic infections at a tertiary care hospital, India

Figure 2 :
Figure 2: Age distribution of HIV positive patients (n = 134) with opportunistic infections at a tertiary care hospital, India

Figure 3 :
Figure 3: Opportunistic infections (n = 222) observed in HIV positive patients (n = 134) at a tertiary care hospital, India International Journal of Medicine and Public Health | Jul-Sep 2014 | Vol 4 | Issue 3

Appendix 2: NACO guidelines for antimicrobial therapy of chronic diarrhea in HIV Positive patients* (2007) Causative organism Recommended antimicrobial drug
, skin infections(2), urinary tract infections (UTI) (2) and pyogenic meningitis (1) were observed.Twenty two cases were observed in adults (mean CD4 count of 269.95 ± 206.71 cells/μl) and eight in children (mean CD4 count of 816.0 ± 682.36 cells/μl).Twenty fi ve cases were observed in patients receiving ART.Amoxicillin and co-amoxiclav were the most frequently prescribed antimicrobial agents.All except two cases of LRTI were cured [Table sulfate + neomycin sulfate + gramicidin ear drops, beclomethasone dipropionate + neomycin + clotrimazole cream and nadifl oxacin cream), analgesics (ibuprofen) and pheniramine maleate.Urinary tract infections were cured with oral fl uoroquinolones in usual doses.Pyogenic meningitis was cured with ceftriaxone, metronidazole, phenytoin, ondansetron, paracetamol and dextrose normal saline followed by cefi xime.Chloroquine was also prescribed initially as empirical treatment for suspected malaria.Of the 22 cases of chronic diarrhea, 21 were observed in adults (mean CD4 count of 208.14 ± 179.94 cells/μl).Of these, 16 were ART naïve.A total of 90 drugs were prescribed (an average of 4.09 drugs/case) [Table2].Patients were treated empirically with more than one antimicrobial agent in 17 (77.2%)cases without prior stool examination.Mean duration of antimicrobial treatment was 10.23 ± 6.60 days.All the drugs were used in the usual recommended doses.Of the 21 cases with assessable outcomes, 17 were cured, three did not improve and one died, while recurrence was observed in one case.
TB, combined form of pulmonary and extra pulmonary TB, tuberculous pleural effusion, TB lymphadenitis (cervical) and TB meningitis were observed.All patients were treated in accordance with the Revised National Tuberculosis Control Programme guidelines as recommended by the NACO.Majority (82.8%) of the patients were cured, while 12 patients (17.1%) died.International Journal of Medicine and Public Health | Jul-Sep 2014 | Vol 4 | Issue 3

Table 2 : Antimicrobial agents prescribed for chronic diarrhea in HIV positive patients (n = 22)
n = Number of cases receiving the treatment.*Formulation prescribed to pediatric patient

Table 3 : Utilization pattern of drugs prescribed for treatment of acute diarrhea in HIV positive patients (n = 18) Drug Formulation Dosage Duration of treatment (days) n
n = Number of cases receiving the treatment (treatment details of one patient was not available).ORS = Oral rehydration salt

Table 4 : Adverse drug reactions (n = 165) due to drugs prescribed for opportunistic infections in HIV positive patients (n = 134)
GI = Gastrointestinal, CNS = Central nervous system.n = Number of adverse events.*Kapadia JD, Desai CK, Solanki MN, Shah AN, Dikshit RK.Effi cacy and safety of antituberculosis drugs in HIV positive patients: A prospective study.Indian J Pharmacol 2013;45:447-52

Table 4 ]
. Most ADRs (n = 149, 90.3%) were associated with anti TB drugs.Majority of ADRs were mild in nature (n = 163, 98.7%) with a severity of level 1 as per the modifi ed Hartwig and Siegel scale.Gastrointestinal ADRs (n = 64) were most frequent.Two serious ADRs (severity level 2 and 3 in one case each) observed included generalized skin rash progressing International Journal of Medicine and Public Health | Jul-Sep 2014 | Vol 4 | Issue 3to peeling of skin due to rifampicin and hepatitis (serum glutamic pyruvic transaminase level of 216 IU/L; normal: 0-35 IU/L) due to isoniazid and/or rifampicin.Suspect drugs were withdrawn in both cases following which the ADRs subsided.Causality assessment with the WHO UMC scale showed that the suspect drug had a possible association with the ADR in 101 cases, probable in 63 and certain in one case.As per the Naranjo score, causality scale showed a possible association in 101 and a probable association in 64 cases.
Tuberculosis, oropharyngeal candidiasis, bacterial infections and chronic diarrhea are the most common opportunistic infections observed in HIV positive patients.Majority of OIs are treated with antimicrobial therapy and supportive drugs in accordance with the NACO and Standard Treatment Guidelines.The number of drugs per prescription is high because of use of multiple drugs and empirical treatment of some cases.Prescription from WHO Essential Medicine List 2011 and prescribing by generic name are the good prescribing practices observed.Majority drugs are dispensed from hospital pharmacy, reducing the cost burden.The drugs used for OI are effective and well tolerated in majority patients, with cure and nonrecurrence observed in most cases.Majority of ADRs are nonserious and do not warrant a change in therapy.Defi nitive diagnosis with appropriate laboratory tests is recommended in cases of bacterial infections and diarrhea.Inclusion of protease inhibitors in fi rst line antiretroviral treatment needs reevaluation in certain OIs considering their protective role in these cases.