Prescription Pattern Monitoring and Off-label Use of Medicines in the Pediatric Department at Tertiary Care Teaching Hospital.

Background Off-label use means the use, concerning dosage, indication, route of administration, or age, of pharmaceutical products which are beyond the terms of the product license. For regulatory bodies and physicians, the global challenge is to achieve optimum pediatric drug therapy. Objective This prospective observational work was carried out in the paediatric department to evaluate the prescribing pattern of medicines and to identify the use of off-label drugs. Method A cross-sectional study was carried in 200 paediatric patients of ages between 0 and 12 years at the paediatric outpatient department of Universal College of Medical Sciences, Bhairahawa. Data were collected by reviewing the prescription paper and the required information was recorded using a structured data collection sheet prepared for study. The prescribing pattern was assessed by using the World Health Organization (WHO) Prescription Indicators and off-label use was assessed using the WHO Children Formulary 2010. Result Among 413 total prescriptions, only 5.56% of drugs were found to be prescribed by generic name, 16.7% of prescriptions were found to be antibiotic and 57.62% of prescribed drugs were from essential drug list. Out of 413 prescribed drugs, 16.46% of drugs were found to be off-label. The maximum extent of off-label prescribing was 51.47% in the child, followed by infants (42.6%) and neonates (5.8%). Fexofenadine; antihistaminic (23.56%), Amoxicillin+clavulanic acid; antibiotic (22.06%) had higher off-label use. Off-label dose (71.8%) was the most common cause of off-label prescribing. Conclusion Off-label prescribing among pediatric patients is common.More eminence data on the safety and efficacy of off-label medicines must be generated to rationalize paediatric pharmacotherapy.

Molecular Epidemiology and Antigenic Characterization of Seasonal Influenza Viruses Circulating in Nepal.

BACKGROUND: Influenza is one of the public health burdens in Nepal and its epidemiology is not clearly understood. The objective of this study was to explore the molecular epidemiology and the antigenic characteristics of the circulating influenza viruses in Nepal. METHODS: A total of 1495 throat swab specimens were collected from January to December, 2014. Real time PCR assay was used for identification of influenza virus types and subtypes. Ten percent of the positive specimens were randomly selected and inoculated onto Madin-Darby Canine Kidney Epithelial cells (MDCK) for influenza virus isolation. All viruses were characterized by the hemagglutination inhibition (HI) assay. RESULTS: Influenza viruses were detected in 421/1495 (28.2%) specimens. Among positive cases, influenza A virus was detected in 301/421 (71.5%); of which 120 (39.9%) were influenza A/H1N1 pdm09 and 181 (60.1%) were influenza A/H3 subtype. Influenza B viruses were detected in 119/421 (28.3%) specimens. Influenza A/H1N1 pdm09, A/H3 and B viruses isolated in Nepal were antigenically similar to the vaccine strain influenza A/California/07/2009(H1N1pdm09), A/Texas/50/2012(H3N2), A/New York/39/2012(H3N2) and B/Massachusetts/2/2012, respectively. CONCLUSIONS: Influenza viruses were reported year-round in different geographical regions of Nepal which was similar to other tropical countries. The circulating influenza virus type and subtypes of Nepal were similar to vaccine candidate virus which could be prevented by currently used influenza vaccine.

Characterization of Seasonal Influenza Virus Type and Subtypes Isolated from Influenza Like Illness Cases of 2012.

Background Seasonal influenza is one of the increasing public health burdens in Nepal. Objective The objective of this study was to isolate and characterize the influenza virus type and subtypes of Nepal. Method A total of 1536 throat swab specimens were collected from January to December 2012. Total ribonucleic acid was extracted using Qiagen viral nucleic acid extraction kit and polymerase chain reaction assay was performed following the US; CDC Real-time PCR protocol. Ten percent of positive specimens were inoculated onto Madin-Darby Canine Kidney cells. Isolates were characterized by using reference ferret antisera. Result Of the total specimens (n=1536), influenza virus type A was detected in 196 (22%) cases; of which 194 (99%) were influenza A (H1N1) pdm09 and 2 (1 %) were influenza A/H3 subtype. Influenza B was detected in 684 (76.9%) cases. Influenza A (H1N1) pdm09, A/H3 and influenza B virus were antigenically similar to the recommended influenza virus vaccine candidate of the year 2012. Although sporadic cases of influenza were observed throughout the year, peak was observed during July to November. Conclusion Similar to other tropical countries, A (H1N1) pdm09, A/H3 and influenza B viruses were co-circulated in Nepal.

Effects of whole-body vibration on acute bone turnover marker responses to resistance exercise in young men.

OBJECTIVE: We investigated acute bone turnover marker (BTM) responses to high-intensity resistance exercise with and without whole-body vibration (WBV) in young men (n=10). METHODS: In this randomized crossover study, subjects performed 2 protocols separated by 2-week wash out periods: 1) resistance exercise only (RE) (3 sets 10 repetitions 80% 1RM for 9 exercises); and 2) WBV + RE (side-alternating vibration platform 5 intermittent, 1-minute bouts 20 Hz, 3.38 mm peak-to-peak displacement followed by RE). Fasting morning blood draws were taken before RE or WBV (PRE), immediately post RE (IP), and 30 minutes post RE (30P). WBV + RE also had a blood draw after the WBV exposure (POST WBV). Blood samples were analyzed for lactate, hematocrit, bone-specific alkaline phosphatase (Bone ALP, U/L), C-terminal telopeptide of type I collagen (CTX-I, ng/mL) and tartrate-resistant acid phosphatase 5b (TRAP5b, U/L). RESULTS: Lactate, hematocrit, and Bone ALP significantly increased (p<0.05) IP for both protocols. Bone resorption markers did not change during RE only. CTX-I significantly decreased POST WBV. TRAP5b increased POST WBV, then significantly decreased at 30P. CONCLUSIONS: Generally, BTM changes to RE only were not significant when adjusted for hemoconcentration. The WBV stimulus altered bone resorption marker but not bone formation marker responses.

Hereditary Spherocytosis with Splenomegaly and Cholelithiasis in a Young Male of Western Region of Nepal - A Case Report.

Hereditary spherocytosis is an autosomal dominant congenital hemolytic anemia due to defect in RBC membrane protein that commonly presents with intermittent jaundice, anemia, abdominal pain, splenomegaly and sometimes cholelithiasis. Due to the membrane defect, there is increased fragility, hemolytic anemia, marked splenomegaly and hyperbilirubinemia. This is a report of an 11 years old male diagnosed case of hereditary spherocytosis who presented with jaundice, splenomegaly and cholelithiasis. He underwent elective open splenectomy and cholecystectomy after prophylactic immunization for capsulated organisms and was advised lifelong oral penicillin prophylaxis post-splenectomy.

Effect of Dexamethasone and Pheniramine Maleate in Patients Undergoing Elective Laparoscopic Cholecystectomy.

INTRODUCTION: Laparoscopic cholecystectomy (LC) is elective surgical procedure for uncomplicated gallstone disease and gallbladder polyp. The objective of this study was to assess the efficacy of Dexamethasone and Pheniramine hydrogen maleate on reducing stress response and pain after surgery in patients undergoing laparoscopic cholecystectomy. METHODS: After obtaining approval from the institutional ethics committee and written informed consent, 120 patients undergoing elective laparoscopic cholecystectomy were enrolled in the study from Sep 2103 to Aug 2014 at Department of Surgery, Manipal College of Medical Sciences, Pokhara, Nepal. Patients were randomized to receive either 8mg/2ml of Dexamethasone + 45.5/2ml Pheniramine hydrogen maleate (treatment group, n= 60) or 5 ml of normal saline (control group, n=60) 90 minutes before skin incision. RESULTS: There was a reduction of total bilirubin, C-reactive protein (CRP) value and Visual Analogue Score (VAS) in treatment group as compared to control group (p <0.05). CONCLUSIONS: Use of Dexamethasone and Pheniramine hydrogen maleate prior to surgical skin incision helps to reduce both postoperative pain and acute physiological stress.

Monitoring the durability of long-lasting insecticidal nets in field conditions in Nepal.

Understanding and improving the durability of long-lasting insecticidal nets (LLINs) in the field is critical for the success of malaria prevention using mosquito nets, as well as contributing to procurement decisions based on the number of years of protection, rather than the current practice of unit cost. Using the recently published guidelines from the World Health Organization (WHO) some progress has been made in the monitoring and assessment of performance of nets in the field. This paper describes the protocol of an ongoing retrospective study of the attrition rate, physical integrity and bioefficacy of three polyester LLIN products that were distributed during 2010 to 2013 in Nepal. It is hoped that robust and auditable data on net survival (physical integrity and bioefficacy) of these three brands in different environments will assist the Nepal National Malaria Control Programme in planning future LLIN-replacement strategies, including behaviour-change communication about LLIN care and maintenance. The advantages and disadvantages of prospective and retrospective cross-sectional approaches are discussed, including appropriate strategies to validate the timing for mass distribution of nets. Similar studies should be done in other countries to (i) track LLIN durability to support management of resupply, and (ii) inform procurement decisions at the global level. New, more predictive, textile laboratory testing is also urgently needed.

Significance of adenosine deaminase in diagnosing tuberculous pleural effusion.

Tuberculosis (TB) is a major public health problem in developing countries including Nepal. One of the common presentations of TB is pleural effusion. The diagnosis of tubercular pleural effusion can be difficult because of the low rate of detecting tubercule bacilli by direct stain and culture of pleural fluid for acid-fast bacilli (AFB). Pleural biopsy can be useful but is invasive and requires experts. In this context, pleural fluid Adenosine Deaminase (ADA) level has been proposed as easy, cheap and highly sensitive test for diagnosis of TB pleural effusion. The present study was undertaken to define the role ofpleural fluid ADA value in accurate diagnosis of TB pleural effusion. A Prospective analysis of 100 patients admitted in Nepal Medical College and teaching Hospital with pleural effusion was done. Pleural fluid ADA level was evaluated in all patients, and significance of pleural fluid ADA level in TB pleural effusion was studied. It was found that mean ADA level in pleural fluid was 105.8 +/- 67.23 U/L in cases of TB, as compared to 16.83 +/- 8.91 U/L in malignancy, 44.53 +/- 32.84 U/L in parapneumonic effusion and 15.94 +/- 4.88 U/L in patients with miscellaneous diagnosis. For a cut-off value of 42.19 U/L for diagnosis of TB pleural effusion, sensitivity was found to be 90.8% and specificity 82.8%. Almost all patients diagnosed to have TB pleural effusion responded completely to anti-tubercular treatment. So, we concluded that pleural fluid ADA analysis could be easy, cheap and highly sensitive and specific test for diagnosis of TB pleural effusion.

Rare synchronous primary large B-cell gastric lymphoma and huge retroperitoneal liposarcoma with inguinal hernia in chronic hepatitis B patient.

Multiple primary neoplasms with synchronous or metachronous presentation are rare, although the incidence has recently increased because of several factors. We present the case of a 53-year-old patient with chronic hepatitis B who presented with abdominal mass, mild abdominal pain, and inguinal hernia. Computed tomography imaging demonstrated diffuse thickening of the gastric antral wall, together with a huge heterogeneous abdominal mass with predominant fat attenuation with septa that showed mild enhancement on contrast-enhanced scans. Distal gastrectomy and wide resection of the retroperitoneal mass was performed. Pathology exam led to a diagnosis of diffuse large B-cell gastric lymphoma with retroperitoneal liposarcoma. This is a rare case of a primary gastric lymphoma with another primary (sarcomatous) malignancy occurring synchronously in same patient.

Study of rifampicin and isoniazid resistance mutation genes of M. tuberculosis isolates in Nepal.

We studied the rifampicin (RIF) and isoniazid (INH) resistant genes in Mycobacterium tuberculosis isolated from sputum samples of re-treated TB cases using phenotypic drug susceptibility test (DST) and rapid molecular method (Genotype; MTBDR plus, Hains Life Science, Nehren, Germany). Of the total 207 isolates included in this study, 90 (42.0%) were RIF resistant, 107 (50.7%) were INH resistant whereas 86 (41.5%) were multidrug resistant (MDR) by DST. According to genotypic analysis, 37.0% (77/207) were RIF resistant, 50.2% (105/207) INH resistant and 70 (33.8%) were MDR. Among the total 90 RIF resistant isolates, 85.5% (77/90) showed mutation in 81 bp of rpoB gene and the mutation locus were distributed as follows; MUT1 Asp516Val (16.7%; 15/90), MUT2A His526Tyr (6.6%; 6/90), MUT2B His526Asp (5.5%; 5/90) and MUT3 Ser531Lue (56.7%; 51/90). Among the total 107 INH resistant isolates, the mutation located in katG gene was 98.1% (105/107) and in inhA MUT1 gene was (16.8%; 18/107). The mutation locus were distributed as follows; MUT1 Ser315Thr (77.6%; 83/107), MUT2 Ser315Ile (3.7%; 4/107) in katG and in inhA MUT1Cys15Thr (16.8%; 18/107). The highest frequency of mutations in rpoB gene was found at the region of codon Ser531Leu (56.7%) while the frequency of mutation in katG and inhA gene were found at the region of codon Ser315Thr (77.6%) and Cyst15Thr (17.1%), respectively. The rapid molecular test kit used in this study was found to be sensitive as well as specific for detection of RIF and INH resistant gene and also helpful in early detection of MDR-TB.

Incidence of incidental carcinoma gall bladder in cases of routine cholecystectomy.

BACKGROUND: Carcinoma of gall bladder is the most common malignancy of the billiary tract. Most of the cases are diagnosed as an incidental case among patients undergoing cholecystectomy. OBJECTIVES: To establish the rate of incidental carcinoma of gall bladder in patients undergoing routine cholecystectomy to study the demographic profile and prognosis of these patients. METHODS: A retrospective study was carried out in Fishtail Hospital and Research Center, Pokhara during 1998-2009. The surgical notes, hospital records and histopathology reports of 783 patients undergoing routine cholecystectomy were studied. RESULTS: Out of 783 cases, gall bladder cancer was detected in 10(1.28%) of cases and was more common in females (M:F ratio 1:2.3) and the mean age of occurrence was 63.8 years. Most of the cases diagnosed were at their early stages and none of them were in T3 and T4 stages. Six of these patients have survived till a mean follow up duration of 23.7 months. CONCLUSION: The rate of incidental carcinoma of gall bladder is 1.28%.

Pulmonary cryptococcosis and tuberculoma mimicking primary and metastatic lung cancer in 18F-FDG PET/CT.

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely incorporated in cancer management. Although, it has increased sensitivity, 18F-FDG is not tissue specific thus posing diagnostic dilemma in certain situations. False positivity in pulmonary nodules have been seen in various inflammatory, infective as well as post operative conditions while false negativity is common with adenomas, low grade lymphomas, bronchoalveolar carcinomas and carcinoid tumors. We present two cases of granulomatous diseases as pulmonary cryptococcosis and tuberculosis showing false positivity in a resected colorectal cancer patient and highlight the importance of recognition of this entity in an endemic region for granulomatous infections.

Seroprevalence of HBV and HCV in blood donors: A study from regional blood transfusion services of Nepal.

BACKGROUND AND OBJECTIVE: Hepatitis B and hepatitis C are significant health problems that might involve the late sequel of liver cirrhosis and hepatocellular carcinoma. A high prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in blood donors poses an increased risk of window period transmission through blood transfusion. The present study aimed to know the seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) among blood donors in regional blood transfusion services of Nepal. MATERIALS AND METHODS: This was a retrospective study conducted among blood donors in Banke (5,211), Morang (5,351), and Kaski (5,995) blood transfusion services. Serum samples were tested for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies using rapid enzyme immunoassays. The donors information was collected via the donor record register through their respective blood transfusion services. The software "Winpepi ver 3.8" was used for statistical analysis. RESULTS: The seroprevalence rate of HBV was highest in the Banke (1.2%) followed by Biratnagar (0.87%) and Kaski (0.35%) (P < 0.0001). The seroprevalence of HCV was highest in the Morang (0.26%) followed by Kaski (0.16%) and Banke (0.11%) (P > 0.05). The seroprevalence of HBV was significantly higher than HCV in all three blood transfusion services. The burden of HBV as well as HCV seems to be higher in male donors (P > 0.05). CONCLUSION: The study revealed that the seroprevalence of HBV was alarmingly higher in two of the three blood transfusion services. Implementation of community-based preventive measures and improved strategies for safe blood supply might prove useful to decrease the seroprevalence.

Epidemiology of malaria in two Eastern districts of Nepal.

BACKGROUNDS: Malaria is one of the major public health problems in Southeast Asia including Nepal having relatively high burden of malaria. Jhapa and Morang districts are malaria endemic plain area of South-eastern part of Nepal. OBJECTIVES: The evaluate the recent epidemiology of malaria situation in Jhapa and Morang districts, which are the districts in eastern Nepal with high transmission of malaria and to assess the knowledge, attitudes and practices of the people in prevention and treatment for malaria infection. MATERIALS AND METHODS: This descriptive cross-sectional study was carried out with volunteer participation of suspected malaria patients seeking care at the government of Nepal managed primary health care centres located in 2 malaria endemic districts in eastern Nepal. Conventional Giemsa stained thick and thin blood smears prepared from finger prick blood were examined following standard protocols. Suspected patients'/attendants' knowledge on malaria, disease symptoms, prevention and control measures were assessed using a structured questionnaire. Chi square and Fisher exact test were used for statistical analysis of the data. RESULTS: Among the total 199 malaria suspected cases studied, 32 (16.1%) cases were confirmed by microscopic findings; where, P. vivax was 12.6% (25/199) and P. falciparum in only 3.1% (6/199). The highest numbers of cases were in age group 20-29 years. Among the total positive cases 75% were male and 37.5% were labourers in occupation. Among the total cases, 32 had provided the history of recent travel to malaria endemic area in India, among them 43.8% (P<0.001) were found to be infected with the malarial parasites (P<0.001). Among the total cases, 69.7% showed some knowledge of malaria, among which fever was the most common symptom mentioned by 68.3%. Occupation (P<0.001) and education (P<0.001) were found significantly associated with the knowledge on mode of transmission. CONCLUSION: Jhapa district showed higher SPR than Morang, which indicated that Jhapa may be more malaria affected than Morang. Knowledge on malaria transmission and preventive measures are still lacking in deep villages, in spite of different efforts of the government. To improve the malaria morbidity in the districts, health education of the most marginalized people through audio visual methods may be beneficial.

Spigelian hernia.

A Spigelian hernia (or lateral ventral hernia) is a hernia through the spigelian fascia, which is the aponeurotic layer between the rectus abdominis muscle medially, and the semilunar line laterally. So far, about 1000 cases have been reported worldwide. These hernias are difficult to diagnose as they do not present with a subcutaneous swelling and have high risk of going for strangulation. We discuss the case of a 36 year old female who presented with history of pain and lumpiness in left lower abdomen, both of which decreased on lying down. She presented to emergency with an episode severe pain at same site which subsided spontaneously. Diagnosis was confirmed on CT scan, plication and onlay prolene mesh repair performed. Spigelian hernias are rare, interparietal type of hernias which have high risk undergoing strangulation. Knowledge of symptoms and signs is vital to diagnosis and treatment of these rare type of hernias.

Comparative evaluation of microscopy and polymerase chain reaction (PCR) for the diagnosis in suspected malaria patients of Nepal.

Microscopy has been the most common technique for the diagnosis of malaria in Nepal. This study was undertaken at CDM, TU, Kathmandu, and Department of Clinical Tropical Medicine, Mahidol University, Bangkok to compare the efficiency of microscopy and PCR for malaria diagnosis in Nepalese context. During July-August 2007, blood samples were collected in glass slides and on filter papers from suspected malaria cases of Kanchanpur, Jhapa and Morang Districts. Sample transportation and storage was done using standard protocol. Microscopy was done at the heath posts in the district in Nepal while Nested PCR using previously standardized primers was carried out at Mahidol University. Among 824 malaria suspected cases, 19.2% (157) were laboratory confirmed as malaria cases (P. vivax 10.9%, P. falciparium 7.7% and 0.4% were of mixed infection) by microscopy. The parasite count range was detected as 320-25020 parasites/microl. Among total 132 samples (114 microscopic positive, 18 negative) were processed for nested PCR. Among microscopic positive samples with increase of the parasitaemia/microl of the blood, the rate of detection by PCR (75.4%) was increased though the PCR failed to detect 2 cases having the parasitaemia 5000-15000/microl of blood however 4 microscopic negative cases were detected as P. vivax infection. Among the microscopy positive samples for P. falciparum, 3 were found P. vivax and 2 were found as mixed infection of Pv and Pf and 6 P. vivax were found positive for P. falciparum by PCR. Two microscopy positive samples for mixed infection were found be positive for one Pv and one Pf by PCR. PCR could be good tool in confirming the clinically strongly suspected but microscopically negative malaria cases and advanced molecular epidemiological studies, although its use in routine diagnosis may not be feasible.

Antibiotic susceptibility of group A Streptococcus isolated from throat swab culture of school children in Pokhara, Nepal.

Group A Streptococcus (GAS) or Streptococcus pyogenes is estimated to be present in 5.0-15.0% of norma individual in the respiratory tract, vagina, skin and anus without any sign of disease. This study was carried out to find out the rate of asymptomatic throat carriage of S. pyogenes and antibiotic susceptibility of the isolates in school children of Pokhara, Western Nepal. A total of 487 randomly selected children younger than 16 years were included in the study. Throat swabs collected were subjected to 5.0% Sheep blood agar supplemented with crystal violet (CVBA).GAS was identified by a-haemolytic colonies, bacitracin sensitivity, cotrimoxazole resistivity, catalase negativity and PYR positivity. Antibiotic susceptibility test was performed on Muller Hinton agar (MHA) containing 5% sheep blood by modified Kirby-Bauer disc diffusion method. Out of total 487 throat swabs, GAS was isolated in 9.2% (n = 45). Among the isolates, 46.6% (n = 21) were from male children where as 53.4% (n = 24) from female children. There was no significant sex difference in colonization of GAS (p > 0.05). Out of 45 isolates, 100.0% isolates were sensitive to antibiotic penicillin-G and amoxycillin where as 15.6%, 6.6%, and 2.2% isolates were resistant to antibiotic erythromycin, tetracycline and azithromycin respectively.

Tuberculosis co-infection in HIV infected persons of Kathmandu.

Tuberculosis is itself a major Public health problem in Nepal and the emergence HIV further complicated the issue. A cross-sectional analytical study was conducted between January 2004 and August 2005, with a general objective to determine the Tuberculosis co-infection status in HIV/AIDS cases of Nepal. Altogether 100 HIV infected persons visiting different Voluntary counseling and testing centers (VCT) and HIV/AIDS care centers located in Kathmandu valley were enrolled in the study. Investigation of tuberculosis was done by standard method prescribed by WHO using sputum specimen. Among 100 HIV infected cases, 66 (66.0%) were males and 34 (34.0%) were females. Majority of the HIV cases were in the age group 21-30 (60.0%) followed by 31-40 (31.0%). Tuberculosis was detected in 23 cases with highest prevalence in the age group 21-30 years (65.2%). No significant relationship could be established between gender and TB (c2 = 0.83, p > 0.01).Significant relationship was established between smoking/alcoholic habit and the subsequent development of tuberculosis (c2 = 7.24, p < 0.05 for smoking habit; c2 = 4.39, p < 0.05 for alcoholic habit at 1 degree of freedom). Among 22 culture positive isolates the predominant was Mycobacterium avium complex (40.9%) followed by M. tuberculosis (27.3%), M. kansasii (18.2%), M. fortuitum (9.1%) and M. chelonae (4.5%). Among the 23 cases of tuberculosis, 22 cases were diagnosed by cultural technique of which 4 cases were smear positive while the remaining one case was diagnosed by direct microscopy although it was culture negative. Smear negative Tuberculosis is found to be alarmingly higher in HIV positive individuals of productive age group. The disease significantly higher in smokers and alcoholics.

Study on CD4 cell responses in HIV infected subjects in Nepal.

HIV infection is characterized by gradual deterioration of immune function mainly the CD4 cells. This study was conducted with the objectives to evaluate the kinetics of CD4 cell depletion and duration of HIV infection and the role of ART in improving CD4 cell levels specifically in Nepalese HIV patients. During April 2005 to March 2006, all together 220 blood samples collected from 110 HIV patients visiting National Public Health Laboratory (NPHL), Kathmandu, were analyzed for CD4 cell count using standard protocol. CD4 cell count before and after starting of anti-retro viral therapy showed significant association (P<0.05). The results of this study clearly indicated that antiretroviral therapy has been playing a role in maintenance CD4 cell counts in HIV infected patients.