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ABSTRACT: Introduction: Routine HIV viral load (VL) testing is not available in India. We compared test performance characteristics of immunologic failure (IF) against the gold standard of virologic failure (VF), examined evolution of drug resistance among those who stayed on a failing regimen because they did not meet criteria for IF and assessed implications for second-line therapy. Methods: Participants on first-line highly active antiretroviral therapy (HAART) in Bangalore, India, were monitored for 24 months at six-month intervals, with CD4 count, VL and genotype, if VL>1000 copies/ml. Standard WHO criteria were used to define IF; VF was defined as having two consecutive VL>1000 copies/ml or one VL>10,000 copies/ml. Resistance was assessed using standard International AIDS Society-USA (IAS-USA) recommendations. Results: Of 522 participants (67.6% male, mean age of 37.5; 85.1% on nevirapine-based and 40.4% on d4T-containing regimens), 57 (10.9%) had VF, 38 (7.3%) had IF and 13 (2.5%) had both VF and IF. The sensitivity of immunologic criteria to detect VF was 22.8%, specificity was 94.6% and positive predictive value was 34.2%. Forty-four participants with VF only continued on their failing first-line regimen; by the end of the study period, 90.9% had M184V, 63.6% had thymidine analogue mutations (TAMs), 34.1% had resistance to tenofovir, and 63.6% had resistance to etravirine. Conclusions: WHO IF criteria have low sensitivity for detecting VF, and the presence of IF poorly predicts VF. Relying on CD4 counts leads to unnecessary switches to second-line HAART and continuation of failing regimens, jeopardizing future therapeutic options. Universal access to VL monitoring would avoid costly switches to second-line HAART and preserve future treatment options.
Journal of the International AIDS Society 01/2013; 16:18449. · 3.26 Impact Factor
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ABSTRACT: Short term efficacy of combination antiretroviral therapy (cART) in resource-constrained settings is comparable to that found in western studies. However, long term data are limited. India has the third largest HIV infected population in the world but the long-term outcome of first line therapy according to the national guidelines has not been evaluated yet. Therefore, we conducted a long-term longitudinal analysis of the efficacy of the national first-line therapy in India from an observational cohort of Indian patients in two different clinical settings.
A total 323 patients who had been on ART for a median of 23 months and achieved virological suppression <100 copies/ml by their study baseline visit, were included and followed for two years. Blood samples were collected every six months for viral load and CD4 count. Drug resistance genotyping was performed when the viral load was >2000 copies/mL. Adherence and treatment interruptions (>48 h) were assessed via self-report. In the studied patients, the median duration of viral suppression was 44 months; 15.8% of patients showed viral rebound, and 2.8% viral failure. Viral rebound or failure was significantly negatively related to perfect adherence (100% adherence and no treatment interruption >48 hrs). Virological re-suppression in the subsequent visit was observed in three patients without any change in therapy despite the presence of key mutations.
Our study reports for the first time, a good long-term response to the first line therapy for a median of nearly four years although a less than perfect adherence increases the risk for treatment failure and subsequent drug resistance development. The empirical findings in this study also indicate the overall success of the Indian ART program in two different settings which likely are representative of other clinics that operate under the national guidelines.
PLoS ONE 01/2013; 8(1):e55421. · 4.09 Impact Factor
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ABSTRACT: Hand, foot, and mouth disease (HFMD) remains a common problem in India, yet its etiology is largely unknown as diagnosis is based on clinical characteristics. There are very few laboratory-based molecular studies on HFMD outbreaks.
The aim of this study was to characterize HFMD-related isolates by molecular techniques.
Between 2005 and 2008, during two documented HFMD outbreaks, 30 suspected HFMD cases presented at the Outpatient Unit of the Department of Dermatology, Christian Medical College (CMC), Vellore. Seventy-eight clinical specimens (swabs from throat, mouth, rectum, anus, buttocks, tongue, forearm, sole, and foot) were received from these patients at the Department of Clinical Virology, CMC, for routine diagnosis of hand, foot, and mouth disease.
Samples from these patients were cultured in Vero and rhabdomyosarcoma (RD) cell lines. Isolates producing enterovirus-like cytopathogenic effect (CPE) in cell culture were identified by a nested reverse transcription-based polymerase chain reaction (RT-PCR) and sequenced. The nucleotide sequences were analyzed using the BioEdit sequence program. Homology searches were performed using the Basic Local Alignment Search Tool (BLAST) algorithm.
The statistical analysis was performed using Epi Info version 6.04b and Microsoft Excel 2002 (Microsoft Office XP).
Of the 30 suspected HFMD cases, only 17 (57%) were laboratory confirmed and Coxsackievirus A16 (CVA16) was identified as the etiological agent in all these cases.
Coxsackievirus A16 (CVA16) was identified as the virus that caused the HFMD outbreaks in Vellore between 2005 and 2008. Early confirmation of HFMD helps to initiate control measures to interrupt virus transmission. In the laboratory, classical diagnostic methods, culture and serological tests are being replaced by molecular techniques. Routine surveillance systems will help understand the epidemiology of HFMD in India.
Journal of global infectious diseases 07/2012; 4(3):153-61.
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ABSTRACT: Understanding the prevalence and correlates of treatment interruptions (TIs) in resource-limited settings is important for improving adherence. HIV-infected adults on highly active antiretroviral therapy (HAART) in Bangalore, India, were enrolled into a prospective cohort study assessing HAART adherence. Participants underwent a structured interview assessing adherence, including occurrence of TI > 48 hours since HAART initiation, length of TI, and self-reported reasons for TI. Serum HIV viral load (VL) and CD4 was measured at 6-month intervals. Baseline data are presented in this article. For the 552 participants mean age was 37.8, 32% were female, 70% were married, 45% earned < $2/day. Eighty-four percent were on nevirapine-based antiretroviral therapy; median duration on HAART was 18 months (range: 1-175) and median CD4 count was 318 cells/µl (IQR: 195-460) at time of study enrollment. Twenty percent (n=110) reported at least one TI; of these, 33% (n=36) reported more than one TI. Median length of most recent TI was 10 days (range: 2-1095). TI was associated with a higher probability of having VL > 400 copies/ml (43% versus 12%; p<0.001). After controlling for time on HAART, TI was more likely among those who were unmarried (OR: 1.9; CI: 1.2-3.1), those treated in a private clinic setting (OR: 2.7; CI: 1.6-4.6 compared with public, and OR: 4.1; CI: 1.9-9.0 compared with public-private setting), and those on efavirenz-based therapy (OR: 2.0; CI: 1.1-3.6). The most common self-reported reason for TI was "side effects" (n=28; 25%), followed by cost of therapy (n=24; 22%). We discuss implications for both individual and structural level interventions to reduce TIs.
AIDS Care 11/2011; 24(6):687-94. · 1.60 Impact Factor
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ABSTRACT: This study was conducted to examine the relationship between adherence, viral load (VL) and resistance among outpatients receiving highly active antiretroviral therapy (HAART) in Bangalore, India. In total, 552 outpatients were recruited and VL testing was conducted for all study participants. HIV-1 genotypic resistance testing was performed for 92 participants with a VL ≥ 1000 copies/ml. Interpretation of resistance mutations was performed according to the Stanford database. Past-month adherence and treatment interruptions for >48 h were assessed via self-report. At baseline, 34 participants (6%) reported <95% past-month adherence and 110 (20%) reported a history of >48 h treatment interruptions. Combining the two adherence measures, 22% of participants were classified as 'suboptimally adherent'. In total, 24% of study participants (n = 132) had a detectable VL. Among the 92 samples sent for resistance testing, 68% had at least one nucleoside reverse transcriptase inhibitor (NRTI) mutation, with M184V being the most common (62%) and with 48% having thymidine analogue mutations. Moreover, 72% had at least one non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation and 23% had three or more NNRTI mutations. Both adherence measures were significantly associated with VL (P < 0.001). Suboptimal adherence was significantly associated with resistance mutations (P < 0.02). The findings illustrate for the first time the strong association between suboptimal adherence, treatment failure and drug resistance to first-line HAART in India. The predictive value of standard adherence measures was improved by including treatment interruption data. The observed mutations can jeopardise future treatment options, especially in light of limited access to second-line treatments. To develop effective adherence interventions, research is needed to examine culturally-specific reasons for treatment interruptions.
International Health 03/2011; 3(1):27-34.
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ABSTRACT: Acute febrile illnesses are a common cause of tropical acute kidney injury (AKI). The incidence and severity of AKI in tropical febrile illnesses and validity of RIFLE classification are unclear.
Consecutive adult inpatients of a tertiary hospital in southern India with tropical acute febrile illness between January 2007 and January 2008 were prospectively studied for the incidence and severity of AKI based on RIFLE classification and its association with mortality and dialysis requirement.
The 367 patients (mean age 39.7±16.9 years; 60% males) with tropical acute febrile illness due to scrub typhus (51.2%), falciparum malaria (10.4%), enteric fever (8.7%), dengue (7.6%), mixed malaria (6.5%), leptospirosis (3.3%), undifferentiated acute febrile illness (8.4%) and others (3.8%) (spotted fever, vivax malaria and Hantaan virus infection) had an overall mortality rate of 12.3%. The incidence of AKI was 41.1%; of which, 17.4%, 9.3% and 14.4% were in the Risk, Injury and Failure classes, respectively. Of the patients, 7.9% required dialysis. Among the Risk, Injury and Failure groups, there was an incremental risk of mortality (OR 6.9, 20.2 and 25.6; P<0.001) and dialysis requirement (OR 3.4, 28.8 and 178.8; P<0.001).
The incidence of AKI in the common tropical acute febrile illnesses in our study such as scrub typhus, falciparum malaria, enteric fever, dengue and leptospirosis is 41.1%. RIFLE classification is valid and applicable in AKI related to tropical acute febrile illnesses, with an incremental risk of mortality and dialysis requirement.
Nephrology Dialysis Transplantation 02/2011; 26(2):524-31. · 3.40 Impact Factor
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ABSTRACT: Early identification and management of treatment failure on highly active antiretroviral therapy (HAART) is crucial in maintaining a sustained response to therapy in HIV infection. However, HIV viral load (VL) and resistance testing, and second-line HAART regimens, are unaffordable to many patients in India, leaving them with limited treatment options. Predictors and reasons for antiretroviral switching, therefore, are likely to differ in settings of varying resources. A one-year, observational study of patients receiving antiretroviral therapy was conducted in a private, non-profit hospital in Bangalore. This paper examines the predictors and consequences of antiretroviral treatment switching in this setting and explores reasons for switching in a subset of patients. Data on demographics, drug regimens, adherence, and physical and psychosocial outcomes were collected quarterly. Tests of VL and CD4 cell counts were performed every six months. One-third of the patients switched therapy during the study period. Baseline predictors of switching included lower CD4 cell counts and more physical symptoms. Contrary to studies in other settings, a high VL did not predict treatment switching, and only a minority of those experiencing drug failure were switched to second-line regimens. Both groups (switchers and non-switchers) improved significantly over time with respect to CD4 counts and psychological well-being, and showed a reduction in physical and depressive symptoms. Any differences between the groups were no longer significant at the end of the study, once we controlled for baseline levels. Clinical, policy, and research implications of these findings are discussed within the context of resource-limited settings.
AIDS Care 02/2011; 23(5):569-77. · 1.60 Impact Factor
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ABSTRACT: Previous research has shown that HIV stigma in India can be characterized by a framework dividing manifestations into enacted (discrimination), vicarious (hearing stories of discrimination), felt normative (perceptions of stigma's prevalence), and internalized stigma (personal endorsement of stigma beliefs). We examined whether this framework could explain associations among stigma, efforts to avoid HIV serostatus disclosure, and depression symptoms in a cohort of 198 HIV-infected individuals from Southern India who were followed up for one year as part of a study of antiretroviral adherence. Prior studies had suggested that disclosure avoidance was a primary outcome of stigma and that impaired well-being was a primary outcome of disclosure avoidance. Analyses from our longitudinal research revealed that the pattern of associations among stigma, disclosure avoidance, and depression symptoms remained consistent over time. Enacted and vicarious stigmas were correlated with felt normative stigma beliefs. In turn, felt normative stigma was correlated with disclosure avoidance. And, enacted stigma, internalized stigma, and disclosure avoidance were all associated with depression symptoms. However, even though the overall framework held together, internalized stigma and depression symptoms dropped significantly over time while other components remained unchanged. These findings suggest that, although HIV stigma may limit disclosure, it does not invariably lead to psychological maladjustment. Amidst ongoing perceptions and experiences of stigma, HIV-positive individuals can achieve significant improvements in their acceptance of the disease and in mental well-being.
Psychology Health and Medicine 01/2011; 16(1):74-85. · 1.18 Impact Factor
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ABSTRACT: The massive scale-up of antiretroviral treatment (ART) access worldwide has brought tremendous benefit to populations affected by HIV/AIDS. Optimising HIV care in countries with diverse medical systems is critical; however data on best practices for HIV healthcare delivery in resource-constrained settings are limited. This study aimed to understand patient characteristics and treatment outcomes from different HIV healthcare settings in Bangalore, India.
Participants from public, private and public-private HIV healthcare settings were recruited between 2007 and 2009 and were administered structured interviews by trained staff. Self-reported adherence was measured using the visual analogue scale to capture adherence over the past month, and a history of treatment interruptions (defined as having missed medications for more than 48 hours in the past three months). In addition, CD4 count and viral load (VL) were measured; genotyping for drug resistance-associated mutations was performed on those who were in virological failure (VL > 1000 copies/ml).
A total of 471 individuals were included in the analysis (263 from the public facility, 149 from the public-private facility and 59 from the private center). Private facility patients were more likely to be male, with higher education levels and incomes. More participants reported ≥ 95% adherence among public and public-private groups compared to private participants (public 97%; private 88%; public-private 93%, p < 0.05). Treatment interruptions were lowest among public participants (1%, 10%, 5% respectively, p < 0.001). Although longer clinic waiting times were experienced by more public participants (48%, compared to private 27%, public-private 19%, p < 0.001), adherence barriers were highest among private (31%) compared with public (10%) and public-private (17%, p < 0.001) participants. Viral load was detectable in 13% public, 22% private and 9% public-private participants (p < 0.05) suggesting fewer treatment failures among public and public-private settings. Drug resistance mutations were found more frequently among private facility patients (20%) compared to those from the public (9%) or public-private facility (8%, p < 0.05).
Adherence and treatment success was significantly higher among patients from public and public-private settings compared with patients from private facilities. These results suggest a possible benefit of the standardized care delivery system established in public and public-private health facilities where counselling by a multi-disciplinary team of workers is integral to provision of ART. Strengthening and increasing public-private partnerships can enhance the success of national ART programs.
BMC Health Services Research 01/2011; 11:277. · 1.66 Impact Factor
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ABSTRACT: Local prevalences of individual diseases influence the prioritization of the differential diagnoses of a clinical syndrome of acute undifferentiated febrile illness (AFI). This study was conducted in order to delineate the aetiology of AFI that present to a tertiary hospital in southern India and to describe disease-specific clinical profiles. An 1-year prospective, observational study was conducted in adults (age >16 years) who presented with an undifferentiated febrile illness of duration 5-21 days, requiring hospitalization. Blood cultures, malarial parasites and febrile serology (acute and convalescent), in addition to clinical evaluations and basic investigations were performed. Comparisons were made between each disease and the other AFIs. A total of 398 AFI patients were diagnosed with: scrub typhus (47.5%); malaria (17.1%); enteric fever (8.0%); dengue (7.0%); leptospirosis (3.0%); spotted fever rickettsiosis (1.8%); Hantavirus (0.3%); alternate diagnosis (7.3%); and unclear diagnoses (8.0%). Leucocytosis, acute respiratory distress syndrome, aseptic meningitis, mild serum transaminase elevation and hypoalbuminaemia were independently associated with scrub typhus. Normal leukocyte counts, moderate to severe thrombocytopenia, renal failure, splenomegaly and hyperbilirubinaemia with mildly elevated serum transaminases were associated with malaria. Rash, overt bleeding manifestations, normal to low leukocyte counts, moderate to severe thrombocytopenia and significantly elevated hepatic transaminases were associated with dengue. Enteric fever was associated with loose stools, normal to low leukocyte counts and normal platelet counts. It is imperative to maintain a sound epidemiological database of AFIs so that evidence-based diagnostic criteria and treatment guidelines can be developed.
Tropical Doctor 10/2010; 40(4):230-4. · 0.66 Impact Factor
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ABSTRACT: Scrub typhus is an important cause of acute undifferentiated febrile illnesses in the Indian subcontinent. Delay in diagnosis and in the initiation of appropriate treatment can result in severe complications such as acute respiratory distress syndrome (ARDS), septic shock and multisystem organ failure culminating in death. We conducted a prospective, observational study to delineate the clinical profile and predictors of mortality in scrub typhus in adults admitted to the medical wards of a tertiary care, referral hospital in South India over a one-year period. The case fatality rate in this study was 12.2%. Metabolic acidosis (odds ratio [OR] 6.1), ARDS (OR 3.6), altered sensorium (OR 3.6) and shock (OR 3.1) were independent predictors of mortality. It appears that scrub typhus has four possible overlapping clinical presentations: mild disease; respiratory predominant disease; central nervous system predominant disease (meningoencephalitis); or sepsis syndrome. Given the telltale presence of an eschar (evident in 45.5%), the characteristic clinical profile and the dramatic therapeutic response to a cheap, yet effective, drug such as doxycycline, medical practitioners in the region should have ample opportunity to reach an early diagnosis and initiate treatment which could, potentially, reduce the mortality and morbidity associated with scrub typhus.
Tropical Doctor 04/2010; 40(3):129-33. · 0.66 Impact Factor
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JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2010; 53(3):415-6. · 4.43 Impact Factor
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ABSTRACT: Study of hantavirus infections in India is in its early stages. As early symptoms of hantavirus disease can be non-specific and the diagnosis confirmed only by laboratory testing, use of appropriate diagnostic tools is important. To improve the diagnosis of hantavirus infections in India, commercial ELISA systems followed by indirect immunofluorescence assays were used to detect anti-hantavirus IgM and IgG in samples from patients with acute febrile illness. Of 347 patients tested, 5.2% showed serological evidence of hantavirus infection. Sequences obtained from patients showing molecular evidence of hantavirus infection were related to Hantaan virus. In the absence of mu-capture ELISA, we recommend the use of combination testing systems in areas non-endemic for hantavirus infections. In India there is an increased risk of rodent-borne infections and the differential diagnosis of undifferentiated febrile illness should include hantavirus infection.
Transactions of the Royal Society of Tropical Medicine and Hygiene 03/2009; 103(4):407-12. · 2.16 Impact Factor
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ABSTRACT: Stigma complicates the treatment of HIV worldwide. We examined whether a multi-component framework, initially consisting of enacted, felt normative, and internalized forms of individual stigma experiences, could be used to understand HIV-related stigma in Southern India. In Study 1, qualitative interviews with a convenience sample of 16 people living with HIV revealed instances of all three types of stigma. Experiences of discrimination (enacted stigma) were reported relatively infrequently. Rather, perceptions of high levels of stigma (felt normative stigma) motivated people to avoid disclosing their HIV status. These perceptions often were shaped by stories of discrimination against other HIV-infected individuals, which we adapted as an additional component of our framework (vicarious stigma). Participants also varied in their acceptance of HIV stigma as legitimate (internalized stigma). In Study 2, newly developed measures of the stigma components were administered in a survey to 229 people living with HIV. Findings suggested that enacted and vicarious stigma influenced felt normative stigma; that enacted, felt normative, and internalized stigma were associated with higher levels of depression; and that the associations of depression with felt normative and internalized forms of stigma were mediated by the use of coping strategies designed to avoid disclosure of one's HIV serostatus.
Social Science [?] Medicine 08/2008; 67(8):1225-35. · 2.70 Impact Factor
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Sara Chandy,
Kumiko Yoshimatsu,
Rainer G Ulrich,
Marc Mertens,
Megumi Okumura,
P Rajendran,
George T John,
Vinohar Balraj,
Jayaprakash Muliyil,
Joy Mammen,
Priya Abraham,
Jiro Arikawa,
Gopalan Sridharan
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ABSTRACT: Hantaviruses are etiological agents of hemorrhagic fever with renal syndrome in many parts of Asia and Europe. There has been no documented case of hantavirus disease from India, although serological evidence exists. We investigated the prevalence of hantavirus in the Indian population and tried to identify potential risk groups for hantavirus infections. The presence of hantavirus-specific IgG antibodies was prospectively evaluated in 661 subjects belonging to different groups, i.e. patients with chronic renal disease, warehouse workers and tribal members engaged in rodent trapping. Healthy volunteer blood donors were included as a control group. Thirty-eight seropositive samples were found using a combination of a commercial ELISA followed by an indirect immunofluorescence assay. Western blot using recombinant Hantaan virus nucleocapsid antigen confirmed the presence of anti-hantavirus IgG in 28 (74%) of the 38 sera tested. This study confirms the presence of hantaviruses in India and warrants increasing awareness of the problems of emerging pathogens and the threats they may pose to the public health system.
Transactions of the Royal Society of Tropical Medicine and Hygiene 02/2008; 102(1):70-4. · 2.16 Impact Factor
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ABSTRACT: Diagnosis of dengue infection is easily and best accomplished by demonstration of specific IgM antibodies in blood. We analyzed retrospectively the dengue IgM seropositivity available for samples obtained over a period of five year (1999-2003) from patients with suspected dengue fever (DF)-like illness to investigate whether there was an overall increase in the dengue IgM prevalence over this period.
Serum samples from a total of 1426 individuals (suspected dengue cases) obtained over five year were tested for dengue specific IgM antibodies. Of the 1426 patients, 693 were adults (>15 yr) and 694 children (<15 yr) (excluding 39 individuals whose age was not known). There were 807 males and 610 females (excluding 9 individuals whose status on sex was unknown).
A total of 423 (29.7%) samples were positive for dengue IgM over the five year period. Overall, there was a significant increase in the percentage of dengue IgM positive individuals over the this period (P<0.001). When the individuals were grouped into children (<15 yr) and adults (>15 yr), a significant increase in the number of dengue IgM positive individuals was noticed only in children (P<0.001) and not in adults. When the individuals were grouped into males and females, a significant increase in the number of dengue IgM positive individuals was noticed in both the sexes (P<0.03). Month-wise analysis of the dengue IgM positivity rates indicated the year-wide occurrence of dengue. A total of 158 (41%) of the dengue IgM positive individuals showed positivity for dengue IgG also suggestive of a secondary heterotypic infection.
The overall significant increase in dengue IgM seropositivity among the suspected cases indicates an increase in dengue virus activity, raising the question whether dengue is emerging/re-emerging as a major health problem in southern India. Increase in probable secondary infection (as evidenced by dual positivity for dengue IgM and IgG) seen in this study is also a point of concern. Such an increase especially in a country like ours where multiple serotypes are prevalent, raises concern over probable increase in the incidences of the more serious DHF/DSS. As this report could well be an underestimate of true incidence, the alarming increase observed in 2003, may be a warning/indication of epidemics to come soon that merits serious consideration.
The Indian journal of medical research 02/2005; 121(2):100-7. · 1.84 Impact Factor
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ABSTRACT: Leflunomide has excellent antiviral activity against cytomegalovirus (CMV) in animal models and is considerably less expensive than intravenous ganciclovir. We used leflunomide in four consenting renal allograft recipients with symptomatic CMV disease, who were unable to afford ganciclovir and would otherwise remain untreated. This is the first report of efficacy of leflunomide in humans with CMV disease. They received loading dose of 100 mg of leflunomide once daily on days 1-3 and then 20 mg once daily for 3 months. All four patients were followed up three times weekly with physical examination, total leukocyte counts, blood urea and serum creatinine for a minimum period of 6 weeks. None of the patients showed drug related adverse events, alteration in cyclosporine levels, or decreased graft function, except one who developed leucopenia. Preliminary data presented suggests that leflunomide therapy for CMV disease is effective and could be used with careful monitoring in allograft recipients who cannot afford intravenous ganciclovir therapy. The duration of treatment and the role of leflunomide in secondary prophylaxis and in situations of ganciclovir resistance need to be studied further.
Transplantation 06/2004; 77(9):1460-1. · 4.00 Impact Factor
