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Antiretroviral Drug Resistance Transmitted in HIV-1 Newly Diagnosed Cuban Patients. April 2013-April 2014

Research Article | Open Access | Volume 7 | Issue 1

  • 1. Department of Virology, Institute of Tropical Medicine “Pedro Kourí”, Cuba
  • 2. National Reference Laboratory for HIV/sida Infections (LISIDA), Cuba
  • 3. Department of Medical Care, Institute of Tropical Medicine “Pedro Kourí”, Cuba
  • 4. Department of Computer Science, Institute of Tropical Medicine “Pedro Kourí”, Cuba
  • 0. The first three authors contributed equally to this research
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Corresponding Authors
Lissette Pérez, Department of Virology, Institute of Tropical Medicine Pedro Kourí (IPK), Autopista Novia del Mediodía, Km 6 ½, La Lisa, Havana, Cuba, Tel: 53 7 2553551; Fax: 53 7 2046051
Abstract

Background: High levels of acquired drug resistance have been reported in Cuban HIV-1 infected patients. The aim of this study is to determine the levels of primary HIV drug resistance in newly diagnosed Cuban´s patients.

Material and methods: Demographic, clinical and laboratory data were collected from 225 newly diagnosed HIV-1 patients from Cuba between April 2013 and April 2014. Sequences of 187 patients were analyzed. The HIV-1 pol gene was sequenced using Sanger sequencing. Drug resistance was interpreted according to the WHO surveillance drug-resistance mutations list, 2009. HIV-1 subtyping was performed using the Rega subtyping tool version 3.

Results: The mean age at sampling time was 33.5 years, 80.7% of the patients were men and the major transmission route was MSM (80.1%). The 27.2% of patients had HIV-1 chronic infection and 72.7% recent infection. The median viral load value was 60,300 RNA copies/mL (16,900 - 133,000), and median CD4+ count value was 359 cells/mm3 (263-558). In the 17.6% (33/187), of the studied viruses, transmitted resistance mutations were detected. Simple nonnucleoside mutants were the most common (1.1%), followed by double class resistance against to nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors (8.0%) and single mutants to the protease inhibitors (2.1%). From the 33 patients with transmitted drug resistances mutations, 22 (66.6%) were MSM, 26 (78.8%), were diagnosed with a recent HIV-1 infection, 13 (39.4%) were from Havana

Conclusions: This study highlights the need of further studies in order to elucidate the factors that influencing the high levels of resistance in newly diagnosed population, in order to take actions toward the possible causes. It also reinforces the need for drug resistance testing in patients that start therapy. It was shown that first-line therapy may not be effective, so in 2016 it is replaced by Atripla.

Citation

Pérez L, Machado LY, Pintos Y, Díaz HM, Kourí V, et al. (2020) Antiretroviral Drug Resistance Transmitted in HIV-1 Newly Diagnosed Cuban Patients. April 2013-April 2014. Clin Res HIV/AIDS 7(1): 1050.

Keywords

•    HIV
•    Cuba
•    New diagnostic patients
•    Drug resistance

ABBREVIATIONS

ART: Antiretroviral Therapy; TDR: Transmitted Drug Resistance; SDRM: Surveillance Drug Resistance Mutations; NRTI: Nucleoside Reverse Transcriptase Inhibitor; NNRTI: Non-Nucleoside Reverse Transcriptase Inhibitor; PI: Protease Inhibitor; CPR: Calibrated Population Resistance; MSM: Men Having Sex With Men; HT: Heterosexual; CI: Chronic Infection; RI: Recent Infection; VL: Viral Load; LAC: Latin-Americans and the Caribbean Countries.

INTRODUCTION

The highly effective antiretroviral therapy has changed the natural history of human immunodeficiency virus ((HIV)/aids), delaying the disease progression and improving the life quality of the HIV patients. The introduction of antiretroviral therapy (ART), in Cuba has resulted in a remarkable improvement of the morbidity and mortality rates in patients infected with HIV type 1 (HIV-1) (Pérez et al. 2004). By the end of 2018 there were more than 34,000 people infected with HIV in Cuba, 86% of them had received ART. The wide access of ART for more than 20 years represents a major concern because of the emergence and spread of antiviral drug resistance, as they could be a threat to sustain the impact of the first-line therapies [1-3].

In HIV-1 Cuban population treated with ART, several factors contributed to high drug resistance levels, such as the prescription of suboptimal regimens containing non-boosted PI, the prolonged exposure to failing therapies due to limited access to laboratory monitoring and the limited options of substitutions antiviral drug if required [4]. These conditions might also increase levels of transmitted drug resistance (TDR).

Previous studies performed in HIV Cuban untreated population have shown high levels of drug resistance (7-20%), although these studied population were not representative of the country and they were not classified in recent or chronic HIV infection [5,6]. In 2018, following the guidelines of the WHO, a new study is conducted that reflects TDR levels of 28.9%) [7].

The aim of this study was to determine the prevalence of TDR in a representative newly diagnosed HIV-1 population in Cuba, from April 2013 to April 2014.

MATERIALS AND METHODS

Study population and design

The number of samples was calculated considering the predicted number of new HIV-1 infection people in Cuba during 1 year (1,800), and the predicted prevalence of TDR. The predicted prevalence of TDR was 25%. Two hundred and twenty-five (225), patients were included in the study, distributed all over the country, from April 2013 to April 2014.

Patients were selected randomly. Epidemiological information was obtained from a questionnaire (including age, place of residence, gender, route of transmission, date of diagnosis and infection).

Sample collection

Three mL of plasma was collected from each patient and sent to the National Reference Laboratory for HIV/aids Diagnostic (LISIDA). The plasma was kept at -80o C until use. Viral load was also determined from 1mL of plasma, at the time of sampling.

We studied 225 samples taking in to consideration the inclusion and exclusion criteria.

Inclusion Criteria: Patient newly diagnosed with HIV infection (less than one year of HIV diagnosis) with viral load ≥ 1,000 RNA copies/mL.

Exclusion Criteria: plasma sample with hemolysis, viral load with less than 1000 RNA copies/mL, treated patients.

Samples (225), were processed in the laboratory of Sexually Transmitted Infections at the Institute of Tropical Medicine “Pedro Kourí” (IPK), and LISIDA laboratories.

Ethics

This research has been approved by the Ethical Committee of IPK, and conforms to the principles laid down in the Declaration of Helsinki [8]. Informed consent was included for every patient who agreed to participate in the study.

Viral load and CD4+ cell count CD4+ cell count

and viral loads were determined at the time of sampling collection. CD4+ cell counts were determined using a FAC Scan (Becton Dickinson, USA). Plasma HIV-1 viral loads were determined using COBAS TaqMan HIV-1 Test (Roche, Mannheim, Germany).

Genotypic drug resistance testing

One mL of plasma was centrifuged at 14,000 rpm for 1 hour; the pellet was resuspended in 140 uL of plasma. Viral RNA extraction was performed manually using the QIAamp Viral RNA Kit (QIAGEN, Hilden, Germany), following the manufacturer’s protocol (www.qiagen.com, Cat No. /ID: 52906). HIV-1 reverse transcription, amplification and population-based bi-directional Sanger sequencing of pol fragments were carried out using a methodology previously described (Aleman et al., 2015). The sequences were edited and assembled using Sequencer, version 4.10 (Gene Codes Corporation, Ann Arbor, MI 48108, USA).

DATA ANALYSIS

HIV subtype was determined using BLAST (www.hiv.lanl. gov/) and confirmed by manual phylogenetic analysis, using CLUSTAL-X and the neighbor-joining method in MEGA version 4 (Kimura’s 2-parameter correction, bootstrap 1000) [9]. Assignment of recombinant genetic forms was done using Simplot version 3.5.1. Tree topology reproducibility was evaluated by bootstrapping using 1000 replications. A phylogenetic group was defined as having a bootstrap value of P>70% [10].

The prevalence of genotypic drug resistance was analyzed using the Calibrated Population Resistance (CPR), tool version 6.0, based on the Surveillance Drug Resistance Mutation (SDRM) list from 2009 [11]. Drugs resistance levels were identified based upon the HIV Rega db genotypic resistance interpretation algorithm version 8.0.2 (http://sierra2.stanford.edu/sierra/ servlet/JSierra?action=algSequenceInput).

Newly diagnosed patients could have a recent or a chronic infection. Recent infection was considered in those patients who were diagnosed as HIV positive on the year after the previous negative HIV serology result. Chronic infections were considered when the evidence of previous negative HIV-1 test was not available.

All provinces were grouped by regions, with exception of Havana Province that was analyzed apart, because there is more than the half of the HIV patients in this province. Thus, we included in the Western region the provinces: Pinar del Río, Isla de la Juventud, Mayabeque, Artemisa and Matanzas; Central region: Cienfuegos, Villa Clara, Sancti Spiritus, Ciego de Avila and Camagüey and Eastern region: Las Tunas, Holguín, Granma, Santiago de Cuba and Guantánamo.

The characteristics of each patient were analyzed using mean, median, interquartile range (IQR) and frequencies (%). Univariate logistic regression was used to determine the factors associated with TDR. The odds ratio (OR) and its 95% confidence interval (CI) were calculated, p-value ≤ 0.05 was considered significant. All statistical analysis was performed using the SPSS statistical software version 18 (SPSS Inc., Chicago, USA).

RESULTS

Patient’s characteristics

Two hundred and twenty five newly diagnosed patients were included in the study. From the 225 processed samples, 187 were successfully sequenced (84.3%). The non-sequenced samples (16.8%), could be related with the viral load level (close to the cut off value of 1000 RNA copies/mL) and freezing and thawing during the transportation.

The mean age of the patients was 33.5 years old (values ranging from 17 to 74 years old). The 80.7% were male and 80.1% of them were men who have sex with men (MSM), 27.2% were diagnosed as chronic infection and 72.7% as recent infection. Seventy two resided in Havana (38.5%), 28 (14.9%) in the Western Region (excluding Havana), 32 (17.1%) in the Central region and 55 (29.4%) in the Eastern region. The median viral load was 60, 400 RNA copies/ml and the median CD4+ lymphocyte count was 359 cells/mm3 (Table 1).

Patients with RI were four times more likely to be within 15-30 years old compared with patients with chronic infection (79/136 vs 13/51, OR=4.051, IC=1.980-8.290, p=0.000), in contrast patients with CI were three times more likely to have 46-61 years old (15/51 vs 15/136, OR=3.361, IC=1.500-7.530, p=0.002, Table 1).

Viral load values over 100,000 copies/mL were more frequently detected in men (57/64 vs 94/123, OR=2.512, CI=1.033-6.109, p=0.05, Table 2), than in women.

Western region was associated with the age ranges 15-30 (20/92 vs 8/95, OR= 3.021, CI= 1.256-7.264, p=0.013); while Havana province was associated with the age range of 46 to 61 years (19/30 vs 53/157, OR = 3.389, CI: 1.503-7.641, p = 0.004).

As expected, HIV viral load (VL) over than 100,000 copies/ mL was associated with CD4+ cells counts below 200 cells/mm3 (16/29 vs 48/158, OR = 2.821, CI= 1.259-6.318, p=0.018).

Subtype distribution

BG recombinants (CRF20_BG, CRF23_BG, CRF24_BG), were the HIV-1 strains more frequently identified (27.8%), followed by subtype B (23.5%), CRF19_cpx (19.5%), unique recombinant forms (URF) (11.2%), and CRF18_cpx (9.6%). Other subtypes like G (4.2%), C (2.1%), H (1.0%), and CRF01_AE (0.5 %) were less frequently detected.

HIV-1 drug resistance

The prevalence of any TDR was 17.6% (33/187). TDR was classified as: 1.1% to reverse transcriptase inhibitor (NRTI) (2/187), 8.0% to non-reverse transcriptase inhibitor (NNRTI) (15/187), 2.1% to protease inhibitor (PI) (4/187), 4.8% double mutants to NRTI+NNRTI (9/187), and 1.6% triple mutants (NRTI+NNRTI+IP) (3/187, table 3).

The NRTI mutations most frequently selected were: M184V (4.2%), T215Y (2.1%), K219Q (2.1%), D67N (1.0%) and L74V (1.0%). The NNRTI mutations resistance more frequently selected were K103N (8.0%), Y181C (5.3%) and G190 (1.6%) and to PI, D30N (1.0%, table3).

Of the 17.6% (33/187) of patients showing HIV-1 TDR mutations, 13.7% (7/51) had CI, and 19.1% (26/136) RI, (p≥ 0.05) (Table 3).

In our study, the presence of TDR associated mutation (ARVs), were associated with 100,000 RNA copies/mL or higher (17/64 vs 16/123, OR=2.419, IC: 1.127-5.193, p=0.02). The presence of TDR associated mutation to each (NRTI, NNRTI, and PI) or double and triple drug family mutants were not associated with any other variables studied (type of infection, sex, route of transmission, region of residence, VL or CD4 + cell count).

ARV resistance

The 2.2% of the analyzed viruses were resistant to NRTI, 9.8% NNRTI and 0.3% PI. The highest resistance levels were observed for nevirapine (NPV), efavirenz (EFV) (13.8%, respectively), and 3TC (4.2%, Figure 1).

Table 1: General characteristics of newly diagnosed HIV-1 patients. April 2013- April 2014.

Characteristics Totala
N (%)
Chronic infection (CI)b
N (%)
Recent infection (RI)c
N (%)
Sequenced samples n (%) 187 (100) 51 (27.2) 136 (72.7)
Age (years)
15-30 
31-45 
46-61 
62-77
92 (49.1) 
63 (33.6)
30(16.0) 
2 (1.0) 
13 (25.4) 
 22 (43.1)
15 (29.4)
1 (1.9)
79 (58.0)
41 (30.1)
15 (11.0) 
1 (0.7)
Male gender 151 (80.7) 40 (78.4) 111 (8.6)
Route of transmission MSM* 121 (80.1) 29 (56.8%) 92 (67.6%)
Region
Havana City 72 (38.5) 21 (41.1) 51 (37.5)
Western region 28 (14.9)) 3 (5.8) 25 (18.3)
Central region 32 (17.1)) 8 (15.6) 24 (17.6)
Eastern region 55 (29.4)) 19 (37.2) 36 (26.4)
CD4 cell count at sampling 
(cells/mm3, median (IQR))
359
(260-560)
370
(262-572)
358
(261.5-558)
HIV-1 viral load at sampling 
(RNA copies/ml, median (IQR))
60,400
(17,425132,500)
83,600
(24,200-175,000)
58,150
(16,200-128,750)
aNewly diagnosed: patients diagnosed with HIV infection during the last year.
bChronic infection: newly diagnosed patients with no evidence with HIV negative test for HIV-1 infection.. 
cRecent infection: newly diagnosed patient with evidence of a previous negative test HIV-1 infection..
MSM: Men who have sex with men
HT: Heterosexual
*MSM was determined based in the total number of men (151)
 

Table 2: Relation between CD4+ cell count and HIV viral load with others variables.

Total
187 
(100%)*
Age year old at diagnosis
N (%)
Gender
N (%)
Route of 
transmission
N (%)
Region
N (%)
15-30 31-45 46-61 62-77 M F MSM HT Havana 
City
Western 
region
Central 
region
Eastern 
region
92 
(49.1)
63 
(33.6)
30 
(16.0)
2
(1.0)
151 
(80.7)
36 
(19.2)
121
(64.7)
66
(35.2)
72 
(38.5)
28
(14.9)
32 (17.1) 55 
(29.4)
                                                             CD4+ cell (cells/mm3)**
<200 10 
(10.8)
17 
(26.9)

(6.6)

(0)
24 
(15.8)

(13.8)
20 
(16.5)

 13.6)
13 
(18.0)

 (17.8)

 (9.3)

 (14.5)
200-350 27 
(29.3)
15 
(23.8)

(26.6)

(0)
39 
(25.8)
11 
(30.5)
28
 (23.1)
22 
(33.3)
17 
(23.6)

(28.5)
10 
(31.2)
15 
(27.2)
351-500 18 
(19.5)
13 
(20.6)

(30.0)

(0)
34 
(22.5)

(19.4)
28
 (23.1)
13 
(19.6)
14 
(19.4)

 (17.8)

(25.0)
14 
(25.4)
>500 26 
(28.2)
15 
(23.8) 
10 
(33.3)

(50.0)
43
 28.4)

(25.0)
36
 (29.7)
16 
 24.2)
19 
(26.3)
6
(21.4)

(28.1)
18 
(32.7)
                                                         HIV-1 viral load RNA copies/ml)
1,000-
10,000
19 
(20.6)

(11.1)

(6.6)

(0)
20
(13.2)

(22.2)
18 
(14.8)
10
 15.1)

 (9.7)

 (21.4)

(6.2)
13 
(23.6)
10,001-
100,000
48
(52.1)
33
 52.3)
14 
(46.6)

(0)
20
(13.2)

(22.2)
58 
(47.9)
37
 56.0)
36 
(50.0)
12 
 (42.8)
25
(78.1)
22 
(40.0)
>100,000 25 
(27.1)
23 
(36.5)
14 
(46.6)

(100)
57
(37.7) 

(19.4)
45
 (37.1)
19 
 28.7)
29 
(40.2)
10 
(35.7)

(15.6)
20 
(36.3)
MSM: Men who have sex with men; HT: Heterosexual
 * All percentages were calculated on basis to the total number of samples (187)
 ** Sixteen patients had not CD4+ cell value, 11 in 15-30 years group, 3 in 31-45 years group, 1 in 45-61 years and 1 in > 61 years group.

Table 3: Characteristics of the patients with HIV-1 transmitted drug resistance.

Infection Age Region of
residence
HIV-1 subtype Sex Route of
transmission
TDR mutations
NRTI NNRTI PI
Chronica 26 Eastern region B F HT   K103N  
Recentb 20 Western 
region
CRF24_BG F HT   G190A N83D
Recent 51 Havana CRF19_cpx M MSM M41L, M184V,
T 215CY
K103N  
Chronic 30 Havana CRF20_BG F HT   K103N  
Recent 31 Havana Unique 
Recombinant 
Form 
M HT   K103N  
Recent 23 Western 
region
Unique 
Recombinant 
Form 
M HT     L23I
Chronic 56 Central region CRF18_cpx F HT   K103N  
Recent 28 Eastern region B M MSM D67N, M184V K103N  
Recent 39 Western 
region
CRF23_BG M MSM D67N, M184V, K219N Y181C  
Recent 58 Havana CRF19_cpx M MSM   K103N  
Chronic 45 Havana CRF18_cpx M MSM   K103N  
Recent 23 Havana Unique 
Recombinant 
Form
M MSM   K101E  
Recent 23 Havana CRF19_cpx M MSM K219N Y181C  
Recent 25 Havana B M MSM L74V, M184V K103N, 
 
 
Recent 24 Central region CRF24_BG M MSM L210W, T215Y K103N, 
Y181C
 
Recent 20 Havana CRF19_cpx M MSM     I47V
Recent 31 Western 
region
CRF20_BG F HT M184V Y181C  
Recent 22 Central region CRF18_cpx M MSM   K101E, 
G190A
 
Recent 37 Central region G M MSM   Y181C  
Recent 19 Central region CRF19_cpx M MSM M41L, L74V, M184V, T215SY K103N D30N
Recent 57 Western 
region 
CRF19_cpx M MSM L74V, M184V, T215Y K103N D30N, N88D
Chronic 17 Eastern region CRF20_BG F HT M184V K101E, 
K103N, 
G190A
 
Recent 29 Central region B M MSM   K103N  
Recent 37 Havana CRF18_cpx M MSM     L90M
Recent 19 Eastern region B F HT   Y181C  
Recent 44 Eastern region Unique 
Recombinant 
Form
M MSM K219Q Y181C  
Recent 22 Havana CRF19_cpx M HT   Y181C  
Recent 49 Central region CRF20_BG M MSM   G190A  
Recent 39 Eastern region G F HT   K103N  
Chronic 42 Eastern region CRF19_cpx M MSM F77L    
Recent 40 Havana B M MSM K219Q    
Chronic 59 Havana CRF19_cpx M MSM   Y181C  
Recent 23 Recent Unique 
Recombinant 
Form
M MSM     F53L
a: Recent infection: newly diagnosed patient with a previous negative HIV-1 test (less than 1 year after negative HIV-1 serology result).
b: Chronic infection: newly diagnosed patient with no previous negative HIV-1 test. 
MSM: Men who have sex with men; HT: Heterosexual; M: Male; F: Female.

 

CONCLUSION

This study confirmed that HIV-1 infection in Cuba is mainly present in males (MSM), who live in Havana city or Western Region. The majority of patients in Cuba are diagnosed during the early stages of HIV-1 infection. We confirmed the high genetic diversity of HIV-1 in the studied samples. The high incidence of TDR in Cuban patients with a recent diagnosis of HIV-1 infection, jeopardize the first-line therapies used in our country. The results confirm the necessity to performance the genotype drug resistances tests in newly diagnosed HIV-1 patients in Cuba.

Acknowledgements: The researchers thank all the patients who agreed to participate in the study, the heads of programs from all over the country who contributed to its successful completion, and the epidemiology department of MINSAP for their support in carrying out the study. This work was supported by the Global Fund to Fight AIDS, Tuberculosis and Malaria.

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Received : 03 Jul 2020
Accepted : 01 Sep 2020
Published : 03 Sep 2020
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Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Arthritis
ISSN : 2475-9155
Launched : 2016
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
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