Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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On Sep 2018




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On Sep 2018




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"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Lucknow
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On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
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Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
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In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : June | Volume : 16 | Issue : 6 | Page : OC01 - OC03 Full Version

A Retrospective Cohort Study on the Risk of Kidney Disease in HIV Positive Individuals Receiving Tenofovir Based Regimens


Published: June 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/50272.16425
Vikash Khandelia, Umashankar Nama, Ashok Mahavar, Anjali Rathore

1. Assistant Professor, Department of Nephrology, Government Medical College and Hospital, Kota, Rajasthan, India. 2. Resident, Department of Nephrology, Government Medical College and Hospital, Kota, Rajasthan, India. 3. Resident, Department of Nephrology, Government Medical College and Hospital, Kota, Rajasthan, India. 4. Resident, Department of Nephrology, Government Medical College and Hospital, Kota, Rajasthan, India.

Correspondence Address :
Dr. Vikash Khandelia,
Government Medical College and Hospital, Kota, Rajasthan, India.
E-mail: vikasnephro@gmail.com

Abstract

Introduction: Exposure to Tenofovir often leads to the development of some irreversible high risk for kidney disease events. In Human Immunodeficiency Virus (HIV) patients, the prolonged treatment with tenofovir use frequently causes mild-to-moderate nephrotoxicity. Hence, there is a need to further investigate the efficacy and the adverse effects associated with tenofovir use to combat the decreased morbidity and mortality associated with the declined kidney function.

Aim: To investigate the risk of kidney disease associated with tenofovir use.

Materials and Methods: A retrospective study was conducted at the tertiary care centre in northern India, from August 2009 to January 2017 and analysed during January to May 2021. The patients with HIV infection who were administered Tenofovir, Lamivudine and Efavirenz (TLE) and Zidovudine, Lamivudine and Nevirapine (ZLN) were included.The patients were divided into two group based on the TLE and ZLN regimen they received. These patients were on a regular follow-up for six months. The data was assessed on the basis of serum creatinine and estimated Glomerular Filtration Rate (eGFR) (using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation), body weight and Cluster of Differentiation (CD4) count.

Results: Out of 703 patients, 364 patients were administered with TLE, while 339 patients received ZLN. In both the groups, the number of patients were between the age 21-40 years was significantly higher, followed by patients between the age 41-60 years. The mean weight and CD4 count of the patients in both the groups significantly increased with the progression of time (p<0.001). The creatinine levels at baseline and at 24 months were comparable in both the groups, p>0.05. The mean eGFR level was significantly lowered in TLE group (112.2 mL/min/1.73 m2) compared to ZLN group (123.5 mL/min/1.73m2) at 24-months follow-up (p<0.001).

Conclusion: Overall results demonstrate that increasing exposure to tenofovir was associated with a higher incidence of CKD. The serum creatinine levels were comparable between the TLE and ZLN group.

Keywords

Acquired immunodeficiency syndrome, Antiretroviral therapy, Chronic kidney disease, Nephrotoxicity

With the advent of Highly Active Antiretroviral Therapy (HAART), HIV is considered a chronic condition, with the majority of HIV infected patients successfully reaching an optimal immune and virological outcome a few months after starting HAART. Treatment with HAART has led to a dramatic increase in the survival of HIV infected patients reducing the incidence of opportunistic infections, Acquired Immunodeficiency Syndrome (AIDS) related malignancies, and improving the patients' quality of life vis-a-vis the pre-HAART era (1).

However, this switch from acute to chronic disease is associated with an increased incidence of Chronic Kidney Disease (CKD),Glomerular Filtration Rate (GFR) (under 60mL/min), which has been reported in up to 60% of HIV-infected patients (2),(3).Globally, in patients with access to Antiretroviral Therapy (ART), CKD in people living with HIV infection is now attributed to non HIV associated conditions and a higher prevalence of CKD and earlier onset is observed in HIV patients as compared to age-matched uninfected individuals (3).

CKD in patients with HIV infection could be due to both HIV and non HIV related factors. One of the factors associated with an increased risk of CKD in HIV positive patients is the use of some antiretrovirals (ARVs) (4).Among all cases of renal impairment in HIV infected patients, around 0.5–14% of renal impairment is caused due to ARVs (4).

Tenofovir Disoproxil Fumarate (TDF) has been shown to be associated with CKD in HIV infected patients (4). Exposure to TDF is an independent risk factor for reduction in renal function (OR 1.67, 95% CI 1.33-2.08) and was strongly associated with renal tubular dysfunction and CKD (3). Additionally, patients receiving third drug along with TDF containing regimens may pose higher risk of CKD (5). It has been demonstrated that patients who received TDF along with ritonavir boosted protease inhibitor are more prone to develop CKD than Non Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) like nevirapine, delavirdine, efavirenz and etravirine (4). The pharmacokinetics of few ART may be modified in patients with HIV infection with CKD; hence, use of TDF based regimens should be avoided in patients with a creatinine clearance of <50 mL/min (6).The chances of developing CKD with HIV infection are even more in older patients with low eGFR (7).

A retrospective study suggests that there is a higher risk of developing eGFR <60mL/min/1.73 m2 with TDF treatment, in western India (8).After considering the adverse side-effects associated with TDF, it is necessary to perform renal parameter monitoring at regular intervals, in order to prevent the severe renal toxicity (9). Hence, this study was conducted in which patients receiving TLE and ZLN treatment were compared, to assess the increased kidney disease risk associated with the tenofovir use and to study the renal outcomes in patients with TDF treatment.

Material and Methods

This was a retrospective study, conducted at the tertiary care centre in northern India, from August 2009 to January 2017. The analysis of the data was done from January to May 2021. A cohort of HIV infected patients who were administered based on ART were enrolled in this study. It was ensured that all the patients’ details remained anonymous and the identities were not revealed at any stage of the study. The study was conducted following the Helsinki guidelines, and under the supervision of the Head of the Department.

Inclusion criteria: Patients of age above 18 years, who were registered at the HIV clinic, receiving ART TLE or ZLN, who were on regular follow-up for at least six months, and whose data were available of at least on six month follow-up were included in this study.

Exclusion criteria: Patients with irregular follow-up/lost to follow-up, whose records were incomplete, had pre-existing CKD, with acute kidney injury, who were on any form of renal replacement therapy and ritonavir-boosted regimen were excluded.

Patients were assessed on the basis of serum creatinine and eGFR (using CKD-EPI equation), body weight and CD4 count.

Statistical Analysis

Statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) version 20.0. Categorical variables were presented as number (percentage) and compared using Pearson’s Chi-square test. Continuous variables were presented as mean (standard deviation) compared using Kolmogorov-Smirnov Z test (for comparison between two groups). A p-value <0.05 was considered as statistically significant.

Results

Of the total 2,590 registered patients, 703 patients were enrolled in this study. Out of the 703, 364 patients were administered with TLE, while 339 patients received ZLN. The number of patients were more in the age group of 21-40 in TLE group (260), as well as in ZLN group (272). In both the groups, majority of patients were male. The demographic characteristics is shown in (Table/Fig 1). The mean weight significantly increased in TLE and ZLN groups from 50 kg at baseline to 54.6 kg at 24 months, and 49.8 kg at baseline to 54.7 kg at 24 months.The mean CD4 levels also increased significantly from baseline (254.0 cells/mm3) to 24 months (488.8 cells/mm3) in TLE group, and in ZLN group, it increased from 197.3 cells/mm3 at baseline to 403.7 cells/mm3 at 24 months (Table/Fig 2). The creatinine levels at baseline and at 24 months were comparable in both the groups, p<0.005. The mean eGFR level was significantly lowered in TLE group (112.2 mL/min/1.73 m2) compared to ZLN group (123.5 mL/min/1.73 m2) at 24-months follow-up (p<0.001).

Discussion

The rising prevalence of CKD in HIV infected individuals is a cause of concern. One of the contributing factors to the development of CKD in this patient population is the use of some ARV especially TDF and some ritonavir-boosted protease inhibitors. In resource-limited settings, routine monitoring of renal function during ART is not recommended. However, the problem of TDF-related nephrotoxicity is being reported increasingly (11).

TDF can sometimes lead to acute kidney injury and proximal tubular dysfunction (12). In the Asia-Pacific region, HIV infected individuals with older age, lower baseline eGFR and PI-based ART were associated with higher risk of renal dysfunction during the use of TDF (11). The magnitude and trajectory of eGFR may vary with calculation of eGFR, done by MDRD or CKD-EPI equations. Patients with baseline eGFR ≥90 mL/min receiving tenofovir experienced significant decline in eGFR level over time, when Modification of Diet in Renal Disease or CKD-EPI equations were used to estimate eGFR. However, patients with eGFR <90 mL/min could not find any significant reduction regardless of which estimating equation was used (13). In settings with limited access to laboratory testing, monitoring guidelines should consider focusing on higher risk patients. It is not clear whether to discontinue the TDF treatment when mild eGFR reduction was observed during treatment. Though patients receiving TDF-based regimen reported high complete or partial renal recovery rate, they discontinued the treatment due to appearance of nephrotoxicity (14).

In the current study, the creatinine level remained stable. Previous literature reported that in TDF induced nephrotoxicity, creatinine level may remain constant with lowering eGFR level which is attributed to tubular dysfunction (15). Secondly, weight gain observed in these patients may be associated with GFR estimation. Serum creatinine has low prediction value for change in eGFR in HIV patients treated with ART. It is recommended that patients who were on ART should be thoroughly monitored for renal impairment during initial four months. However, appearance of renal impairment after four months of tenofovir based ART regimen is not so common (16).

Incidence of renal loss was higher among women and patients with CD4 nadir <200 cell/mm3 who use tenofovir as ART (17). In the present study, CD4 count did not decrease, which could be the reason for stable creatinine levels.

When TLE and ZLN treatment modalities are compared, it is seen that the ADR associated with ZLN are more severe than the ADR in TLE (18). The incidence of opportunistic infections was also higher in ZLN group when compared to TLE group, however a retrospective study suggests that both TLE and ZLN are equally effective treatment in improving the immunological status of HIV infected patients (19). Zidovudine is a well-absorbed deoxythymidine analog, which can also cross the Blood Brain Barrier (BBB) (20), and tenofovir is a nucleotide analogue having broad tissue distribution because of its low-molecular size (21). The ZLN regimen is a very effective treatment modality in HIV-infected patients. However, the only limitation of ZLN regimen is its possibility to develop haematological toxicity. Hence, it should be used cautiously in patients with haematological disorders like anaemia (22).

Clinicians may use monitoring tools including Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) risk score for, routine measurements of eGFR, and proteinuria to identify risk factors (23). Sometimes individuals may require an intervention.Long-term renal safety has been associated with use of Tenofovir Alafenamide (TAF), alternative of TDF. Outcomes of renal safety are still awaited for the long-term use of TAF but available short-term data suggest that little decline in eGFR level with low risk of proteinuria. Alternative dual therapy antiretroviral regimen is a promising therapy and exclusion of nucleoside (tide) reverse transcriptase class and PI/rs can help to reduce burden of drug which further reduce the toxicity. But the long-term safety outcomes of these dual therapies are still unknown. Further prospective studies are required to address preventive measures and predictive factors associated with renal impairment in HIV infected patients (24).

Limitation(s)

This was a retrospective, comparative study from a single institution. Multicentric, randomised trials with a larger sample size and longer follow-up are necessary to confirm these findings.

Conclusion

Overall results demonstrate that increasing exposure to tenofovir was associated with a higher incidence of CKD. The levels of serum creatinine and CD4 were comparable between the TLE and ZLN group.

References

1.
Tseng A, Seet J, Phillips EJ. The evolution of three decades of antiretroviral therapy: Challenges, triumphs and the promise of the future. Br J Clin Pharmacol. 2015;79:182-94. [crossref] [PubMed]
2.
Juega-Mariño J, Bonjoch A, Pérez-Alvarez N, Negredo E, Bayes B, Bonet J, et al. Prevalence, evolution, and related risk factors of kidney disease among Spanish HIV-infected individuals. Medicine (Baltimore). 2017;96:e7421. [crossref] [PubMed]
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Cristelli MP, Trullàs JC, Cofán F, Rico N, Manzardo C, Ambrosioni J, et al. Prevalence and risk factors of mild chronic renal failure in HIV-infected patients: Influence of female gender and antiretroviral therapy. Braz J Infect Dis. 2018;22:193-201. [crossref] [PubMed]
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Cuzin L, Pugliese P, Allavena C, Rey D, Chirouze C, Bani-Sadr F, et al. Antiretroviral therapy as a risk factor for chronic kidney disease: Results from traditional regression modeling and causal approach in a large observational study. PLoS One. 2017;12:e0187517. [crossref] [PubMed]
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LaFleur J, Bress AP, Myers J, Rosenblatt L, Crook J, Knippenberg K, et al. Tenofovir-associated bone adverse outcomes among a US National Historical Cohort of HIV-Infected Veterans: Risk modification by concomitant antiretrovirals. Infect Dis Ther. 2018;7:293-308. [crossref] [PubMed]
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Cattaneo D, Gervasoni C. Novel antiretroviral drugs in patients with renal impairment: Clinical and pharmacokinetic considerations. Eur J Drug Metab Pharmacokinet. 2017;42:559-72. [crossref] [PubMed]
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Woolnough EL, Hoy JF, Cheng AC, Walker RG, Chrysostomou A, Woolley I, et al. Predictors of chronic kidney disease and utility of risk prediction scores in HIV-positive individuals. AIDS. 2018;32:1829-35. [crossref] [PubMed]
8.
Pujari SN, Smith C, Makane A, Youle M, Johnson M, Bele V, et al. Higher risk of renal impairment associated with tenofovir use amongst people living with HIV in India: A comparative cohort analysis between Western India and United Kingdom. BMC Infect Dis. 2014;14:173. [crossref] [PubMed]
9.
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DOI and Others

DOI: 10.7860/JCDR/2022/50272.16425

Date of Submission: May 09, 2021
Date of Peer Review: Aug 27, 2021
Date of Acceptance: Mar 08, 2022
Date of Publishing: Jun 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? No
• Was informed consent obtained from the subjects involved in the study? NA
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: May 10, 2021
• Manual Googling: Mar 07, 2022
• iThenticate Software: Mar 24, 2022 (17%)

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