Generic placeholder image

Current HIV Research

Editor-in-Chief

ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Research Article

Can In-house HIV-2 Viral Load Assay be a Reliable Alternative to Commercial Assays for Clinical and Therapeutic Monitoring?

Author(s): Veena Vadhini Ramalingam, Gnanadurai John Fletcher, Anand Kasirajan, John Paul Demosthenes, Priscilla Rupali, George Mannil Varghese, Susanne Alexander Pulimood, Grace Rebekah and Rajesh Kannangai*

Volume 20, Issue 4, 2022

Published on: 02 September, 2022

Page: [274 - 286] Pages: 13

DOI: 10.2174/1570162X20666220609155237

Price: $65

Abstract

Background: Currently, there is a global contemplation to end the AIDS epidemic by 2030. HIV-2 poses unique challenges to this end. The burden of HIV-2 is higher in resource-limited countries, and it is intrinsically resistant to NNRTI drugs. In addition, there is no FDA-approved plasma viral load assay to monitor disease progression and therapeutic efficacy. To overcome these challenges, we have developed and evaluated an in-house quantitative HIV-2 viral load assay.

Methods: Blood samples were collected from 28 HIV-2 treatment-naïve monoinfected individuals and tested using an in-house qPCR HIV-2 viral load assay. The extracted RNA was amplified using Quantifast pathogen + IC kit.

Results: The in-house qPCR has a limit of detection of 695 copies/ml. The intra- and inter-assay variation (% CV) of the assay was 0.61 and 0.95, respectively. The in-house assay quantified HIV-2 NIBSC accurately (1000 IU) with a mean of 1952 copies/mL. Among the 28 samples tested by in-house qPCR assay, 11 (39.2%) samples were quantified, whereas 17 (60.7%) samples were not detected. In comparison with Altona RealStar HIV-2 RT PCR and Exavir Load RT assay, the results were 96.4% and 69.6% concordant, respectively. No significant (p = 0.99 and p = 0.13) difference in quantifying viral load between the three assays. Based on clinical and immunological (CD4) staging, the performance characteristics were comparable.

Conclusion: To the best of our knowledge, this is the first in-house qPCR developed in India. The performance characteristics of the in-house assay are comparable to the commercial assays, and they can be used assertively to monitor HIV-2 patients.

Keywords: HIV-1, HIV-2, quantitative real-time polymerase chain reaction, viral load, NNRTI.

Graphical Abstract

[1]
Ellis RR. Types and Strains of HIV. WebMD Available from: https://www.webmd.com/hiv-aids/types-strains-hiv
[2]
HIV-1 vs. HIV-2: Differences and similarities. 2018. Available from: https://www.medicalnewstoday.com/articles/323893 [cited 2021 Mar 30].
[3]
HIV-1 and HIV-2. aidsmapcom Available from: https://www. aidsmap.com/about-hiv/hiv-1-and-hiv-2 [cited 2021 Mar 26].
[4]
Epidemiology of HIV/AIDS in the United States. Available from: http://hivinsite.ucsf.edu/insite?page=kb-01-03 [cited 2021 Mar 28].
[5]
Current Trends Update: HIV-2 Infection United States. Available from: https://www.cdc.gov/mmwr/preview/mmwrhtml/00001446.htm [cited 2021 Mar 28].
[6]
Human Immunodeficiency Virus 2 Infection - an overview. ScienceDirect Topics Available from: https://www.sciencedirect.com/topics/medicine-and-dentistry/human-immunodeficiency-virus-2-infection [cited 2021 Mar 28].
[7]
Valadas E, França L, Sousa S, Antunes F. 20 years of HIV-2 infection in Portugal: Trends and changes in epidemiology. Clin Infect Dis 2009; 48(8): 1166-7.
[http://dx.doi.org/10.1086/597504] [PMID: 19292644]
[8]
Babu PG, Saraswathi NK, Devapriya F, John TJ. The detection of HIV-2 infection in southern India. Indian J Med Res 1993; 97: 49-52.
[PMID: 8505073]
[9]
Rübsamen-Waigmann H, Briesen HV, Maniar JK, Rao PK, Scholz C, Pfützner A. Spread of HIV-2 in India. Lancet 1991; 337(8740): 550-1.
[http://dx.doi.org/10.1016/0140-6736(91)91333-P] [PMID: 1671908]
[10]
Sharp PM, Hahn BH. The evolution of HIV-1 and the origin of AIDS. Philos Trans R Soc Lond B Biol Sci 2010; 365(1552): 2487-94.
[http://dx.doi.org/10.1098/rstb.2010.0031] [PMID: 20643738]
[11]
Lemey P, Pybus OG, Wang B, Saksena NK, Salemi M, Vandamme AM. Tracing the origin and history of the HIV-2 epidemic. Proc Natl Acad Sci USA 2003; 100(11): 6588-92.
[http://dx.doi.org/10.1073/pnas.0936469100] [PMID: 12743376]
[12]
Hirsch VM, Olmsted RA, Murphey-Corb M, Purcell RH, Johnson PR. An African primate lentivirus (SIVsm) closely related to HIV-2. Nature 1989; 339(6223): 389-92.
[http://dx.doi.org/10.1038/339389a0] [PMID: 2786147]
[13]
Gao F, Yue L, White AT, et al. Human infection by genetically diverse SIVSM-related HIV-2 in west Africa. Nature 1992; 358(6386): 495-9.
[http://dx.doi.org/10.1038/358495a0] [PMID: 1641038]
[14]
Chen Z, Luckay A, Sodora DL, et al. Human immunodeficiency virus type 2 (HIV-2) seroprevalence and characterization of a distinct HIV-2 genetic subtype from the natural range of simian immunodeficiency virus-infected sooty mangabeys. J Virol 1997; 71(5): 3953-60.
[http://dx.doi.org/10.1128/jvi.71.5.3953-3960.1997] [PMID: 9094672]
[15]
Chen Z, Telfier P, Gettie A, et al. Genetic characterization of new West African simian immunodeficiency virus SIVsm: Geographic clustering of household-derived SIV strains with human immunodeficiency virus type 2 subtypes and genetically diverse viruses from a single feral sooty mangabey troop. J Virol 1996; 70(6): 3617-27.
[http://dx.doi.org/10.1128/jvi.70.6.3617-3627.1996] [PMID: 8648696]
[16]
Nyamweya S, Hegedus A, Jaye A, Rowland-Jones S, Flanagan KL, Macallan DC. Comparing HIV-1 and HIV-2 infection: Lessons for viral immunopathogenesis. Rev Med Virol 2013; 23(4): 221-40.
[http://dx.doi.org/10.1002/rmv.1739] [PMID: 23444290]
[17]
Esbjörnsson J, Jansson M, Jespersen S, et al. HIV-2 as a model to identify a functional HIV cure. AIDS Res Ther 2019; 16(1): 24.
[http://dx.doi.org/10.1186/s12981-019-0239-x] [PMID: 31484562]
[18]
Ariën KK, Vanham G, Arts EJ. Is HIV-1 evolving to a less virulent form in humans? Nat Rev Microbiol 2007; 5(2): 141-51.
[http://dx.doi.org/10.1038/nrmicro1594] [PMID: 17203103]
[19]
Vidya Vijayan KK, Karthigeyan KP, Tripathi SP, Hanna LE. Pathophysiology of cd4+ t-cell depletion in HIV-1 and HIV-2 infections. Front Immunol 2017; 8: 580. Available from: https://www.ncbi. nlm. nih. gov/pmc/articles/PMC5440548/ [Internet].
[http://dx.doi.org/10.3389/fimmu.2017.00580] [PMID: 28588579]
[20]
Salwe S, Singh A, Padwal V, et al. Immune signatures for HIV-1 and HIV-2 induced CD4+T cell dysregulation in an Indian cohort. BMC Infect Dis 2019; 19(1): 135.
[http://dx.doi.org/10.1186/s12879-019-3743-7] [PMID: 30744575]
[21]
Wittkop L, Arsandaux J, Trevino A, et al. CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients: A multinational, multicohort European study. J Antimicrob Chemother 2017; 72(10): 2869-78.
[http://dx.doi.org/10.1093/jac/dkx210] [PMID: 29091198]
[22]
Poulsen AG, Aaby P, Larsen O, et al. 9-year HIV-2-associated mortality in an urban community in Bissau, west Africa. Lancet 1997; 349(9056): 911-4.
[http://dx.doi.org/10.1016/S0140-6736(96)04402-9] [PMID: 9093252]
[23]
Jaffar S, Grant AD, Whitworth J, Smith PG, Whittle H. The natural history of HIV-1 and HIV-2 infections in adults in Africa: A literature review. Bull World Health Organ 2004; 82(6): 462-9.
[PMID: 15356940]
[24]
Whittle H, Morris J, Todd J, et al. HIV-2-infected patients survive longer than HIV-1-infected patients. AIDS 1994; 8(11): 1617-20.
[http://dx.doi.org/10.1097/00002030-199411000-00015] [PMID: 7848600]
[25]
Ekouevi DK, Balestre E, Coffie PA, et al. Characteristics of HIV-2 and HIV-1/HIV-2 dually seropositive adults in west africa presenting for care and antiretroviral therapy: The iedea-west africa hiv-2 cohort study. PLoS One 2013; 8(6): e66135. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3688850/ [Internet].
[http://dx.doi.org/10.1371/journal.pone.0066135] [PMID: 23824279]
[26]
Peterson K, Jallow S, Rowland-Jones SL, de Silva TI. Antiretroviral therapy for HIV-2 infection: Recommendations for management in low-resource settings. Aids Res Treat 2011; 2011: 463704.
[http://dx.doi.org/10.1155/2011/463704] [PMID: 21490779]
[27]
Smith RA, Anderson DJ, Pyrak CL, Preston BD, Gottlieb GS. Antiretroviral drug resistance in HIV-2: Three amino acid changes are sufficient for classwide nucleoside analogue resistance. J Infect Dis 2009; 199(9): 1323-6.
[http://dx.doi.org/10.1086/597802] [PMID: 19358668]
[28]
Resistance to non-nucleoside reverse transcriptase inhibitors - Antiretroviral Resistance in Clinical Practice. NCBI Bookshelf Available from: https://www.ncbi.nlm.nih.gov/books/NBK2249/ [cited 2021 Oct 20].
[29]
Ren J, Bird LE, Chamberlain PP, Stewart-Jones GB, Stuart DI, Stammers DK. Structure of HIV-2 reverse transcriptase at 2.35-A resolution and the mechanism of resistance to non-nucleoside inhibitors. Proc Natl Acad Sci USA 2002; 99(22): 14410-5.
[http://dx.doi.org/10.1073/pnas.222366699] [PMID: 12386343]
[30]
Witvrouw M, Pannecouque C, Switzer WM, Folks TM, De Clercq E, Heneine W. Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: Implications for treatment and postexposure prophylaxis. Antivir Ther 2004; 9(1): 57-65.
[http://dx.doi.org/10.1177/135965350400900115] [PMID: 15040537]
[31]
Kanki PJ, Travers KU. MBoup S, et al. Slower heterosexual spread of HIV-2 than HIV-1. Lancet 1994; 343(8903): 943-6.
[http://dx.doi.org/10.1016/S0140-6736(94)90065-5] [PMID: 7909009]
[32]
Marlink R, Kanki P, Thior I, et al. Reduced rate of disease development after HIV-2 infection as compared to HIV-1. Science 1994; 265(5178): 1587-90.
[http://dx.doi.org/10.1126/science.7915856] [PMID: 7915856]
[33]
Gottlieb GS, Sow PS, Hawes SE, Ndoye I, Redman M, Coll-Seck AM, et al. Equal plasma viral loads predict a similar rate of cd4± t cell decline in human immunodeficiency virus (hiv) type 1- and hiv-2-infected individuals from Senegal, West. Afr J Infect Dis 2002; 185(7): 905-14.
[http://dx.doi.org/10.1086/339295] [PMID: 11920314]
[34]
Viral Load - an overview. ScienceDirect Topics Available from: https://www.sciencedirect.com/topics/immunology-and-microbiology/viral-load [cited 2021 Mar 30].
[35]
Tchounga B, Ekouevi DK, Balestre E, Dabis F. Mortality and survival patterns of people living with HIV-2. Curr Opin HIV AIDS 2016; 11(5): 537-44.
[http://dx.doi.org/10.1097/COH.0000000000000299] [PMID: 27254747]
[36]
Campbell-Yesufu OT, Gandhi RT. Update on human immunodeficiency virus (HIV)-2 infection. Clin Infect Dis 2011; 52(6): 780-7.
[http://dx.doi.org/10.1093/cid/ciq248] [PMID: 21367732]
[37]
Plasma HIV-1 RNA (Viral Load) and CD4 Count Monitoring Laboratory Testing Adult and Adolescent ARV. AIDSinfo Available from: https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/458/plasma-hiv-1-rna--viral-load--and-cd4-count-monitoring [cited 2020 May 21].
[38]
Gupta V, Gupta S. Laboratory markers associated with progression of HIV infection. Indian J Med Microbiol 2004; 22(1): 7-15.
[http://dx.doi.org/10.1016/S0255-0857(21)02944-3] [PMID: 17642679]
[39]
Vajpayee M, Mohan T. Current practices in laboratory monitoring of HIV infection. Indian J Med Res 2011; 134(6): 801-22.
[http://dx.doi.org/10.4103/0971-5916.92627] [PMID: 22310815]
[40]
Criteria I of M (US) C on SSHD. Low CD4 Count as an Indicator of Disability [Internet]. HIV and Disability: Updating the Social Security Listings. National Academies Press (US) 2010. Available from: https://www.ncbi.nlm.nih.gov/books/NBK209955/ [cited 2021 Mar 29].
[41]
Lavreys L, Baeten JM, Chohan V, et al. Higher set point plasma viral load and more-severe acute HIV type 1 (HIV-1) illness predict mortality among high-risk HIV-1-infected African women. Clin Infect Dis 2006; 42(9): 1333-9.
[http://dx.doi.org/10.1086/503258] [PMID: 16586394]
[42]
Shoko C, Chikobvu D. A superiority of viral load over CD4 cell count when predicting mortality in HIV patients on therapy. BMC Infect Dis 2019; 19(1): 169.
[http://dx.doi.org/10.1186/s12879-019-3781-1] [PMID: 30770728]
[43]
Rowley CF. Developments in CD4 and viral load monitoring in resource-limited settings. Clin Infect Dis 2014; 58(3): 407-12.
[http://dx.doi.org/10.1093/cid/cit733] [PMID: 24218101]
[44]
Calmy A, Ford N, Hirschel B, et al. HIV viral load monitoring in resource-limited regions: Optional or necessary? Clin Infect Dis 2007; 44(1): 128-34.
[http://dx.doi.org/10.1086/510073] [PMID: 17143828]
[45]
Andersson S, Norrgren H, da Silva Z, et al. Plasma viral load in HIV-1 and HIV-2 singly and dually infected individuals in Guinea-Bissau, West Africa: Significantly lower plasma virus set point in HIV-2 infection than in HIV-1 infection. Arch Intern Med 2000; 160(21): 3286-93.
[http://dx.doi.org/10.1001/archinte.160.21.3286] [PMID: 11088091]
[46]
Peruski AH, Wesolowski LG, Delaney KP, et al. Trends in HIV-2 diagnoses and use of the hiv-1/hiv-2 differentiation test - United States, 2010-2017. MMWR Morb Mortal Wkly Rep 2020; 69(3): 63-6. Available from: https://www.cdc.gov/mmwr/volumes/69/wr/mm6903a2.htm [Internet].
[http://dx.doi.org/10.15585/mmwr.mm6903a2] [PMID: 31971928]
[47]
Lim K, Park M, Lee MH, Woo HJ, Kim JB. Development and assessment of new RT-qPCR assay for detection of HIV-1 subtypes. Biomed Sci Lett 2016; 22(3): 83-97.
[http://dx.doi.org/10.15616/BSL.2016.22.3.83]
[48]
Jagodzinski LL, Manak MM, Hack HR, Liu Y, Peel SA. Performance evaluation of a laboratory developed PCR test for quantitation of HIV-2 viral RNA. PLoS One 2020; 15(2): e0229424.
[http://dx.doi.org/10.1371/journal.pone.0229424] [PMID: 32109949]
[49]
HIV-2: still off the radar for India’s 90-90-90 targets. Indian Journal of Medical Research Available from: https://journals. lww.com/ijmr/Fulltext/2021/07000/HIV_2__still_off_the_radar_for_India_s_90_90_90.7.aspx [cited 2022 Jan 31].
[50]
Ingole NA, Sarkate PP, Paranjpe SM, Shinde SD, Lall SS, Mehta PR. HIV-2 Infection: Where are we today? J Glob Infect Dis 2013; 5(3): 110-3.
[http://dx.doi.org/10.4103/0974-777X.116872] [PMID: 24049365]
[51]
Zhang D, Lou X, Yan H, et al. Metagenomic analysis of viral nucleic acid extraction methods in respiratory clinical samples. BMC Genomics 2018; 19(1): 773.
[http://dx.doi.org/10.1186/s12864-018-5152-5] [PMID: 30359242]
[52]
Piralla A, Girello A, Premoli M, Baldanti F. A new real-time reverse transcription-PCR assay for detection of human enterovirus 68 in respiratory samples. J Clin Microbiol 2015; 53(5): 1725-6.
[http://dx.doi.org/10.1128/JCM.03691-14] [PMID: 25694533]
[53]
MacNeil A, Sankalé JL, Meloni ST, Sarr AD, Mboup S, Kanki P. Genomic sites of human immunodeficiency virus type 2 (HIV-2) integration: Similarities to HIV-1 in vitro and possible differences in vivo. J Virol 2006; 80(15): 7316-21.
[http://dx.doi.org/10.1128/JVI.00604-06] [PMID: 16840312]
[54]
Padaki PA, Sachithanandham J, Isaac R, et al. The performance of reverse transcriptase assay for the estimation of the plasma viral load in HIV-1 and HIV-2 infections. Infect Dis (Lond) 2016; 48(6): 467-71.
[http://dx.doi.org/10.3109/23744235.2015.1122832] [PMID: 26654354]
[55]
Greengrass V, Lohman B, Morris L, et al. Assessment of the low-cost Cavidi ExaVir Load assay for monitoring HIV viral load in pediatric and adult patients. J Acquir Immune Defic Syndr 2009; 52(3): 387-90.
[http://dx.doi.org/10.1097/QAI.0b013e3181b05f62] [PMID: 19617845]
[56]
Greengrass VL, Turnbull SP, Hocking J, et al. Evaluation of a low cost reverse transcriptase assay for plasma HIV-1 viral load monitoring. Curr HIV Res 2005; 3(2): 183-90.
[http://dx.doi.org/10.2174/1570162053506955] [PMID: 15853722]
[57]
Malmsten A, Shao XW, Aperia K, et al. HIV-1 viral load determination based on reverse transcriptase activity recovered from human plasma. J Med Virol 2003; 71(3): 347-59.
[http://dx.doi.org/10.1002/jmv.10492] [PMID: 12966539]
[58]
TOPO® TA CloningTM Kit From Invitrogen. 2007. Available from: http://www.biocompare.com/Product-Reviews/40586-TOPO -TA-Cloning-Kit-From-Invitrogen/ [cited 2020 May 23].
[59]
Keiser O, MacPhail P, Boulle A, et al. Accuracy of WHO CD4 cell count criteria for virological failure of antiretroviral therapy. Trop Med Int Health 2009; 14(10): 1220-5.
[http://dx.doi.org/10.1111/j.1365-3156.2009.02338.x] [PMID: 19624478]
[60]
Kimmel AD, Weinstein MC, Anglaret X, et al. Laboratory monitoring to guide switching antiretroviral therapy in resource-limited settings: Clinical benefits and cost-effectiveness. J Acquir Immune Defic Syndr 2010; 54(3): 258-68.
[http://dx.doi.org/10.1097/QAI.0b013e3181d0db97] [PMID: 20404739]
[61]
Monitoring of human immunodeficiency virus infection in resource- constrained countries. clinical infectious diseases. Available from: https://academic.oup.com/cid/article/37/Supplement_1/S25/ 351431 [cited 2021 Jun 3].
[62]
Mermin J, Ekwaru JP, Were W, et al. Utility of routine viral load, CD4 cell count, and clinical monitoring among adults with HIV receiving antiretroviral therapy in Uganda: Randomised trial. BMJ 2011; 343: d6792.
[http://dx.doi.org/10.1136/bmj.d6792] [PMID: 22074711]
[63]
Roberts T, Cohn J, Bonner K, Hargreaves S. Scale-up of routine viral load testing in resource-poor settings: Current and future implementation challenges. Clin Infect Dis 2016; 62(8): 1043-8.
[http://dx.doi.org/10.1093/cid/ciw001] [PMID: 26743094]
[64]
Karade SK, Ghate MV, Chaturbhuj DN, et al. Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. Medicine (Baltimore) 2016; 95(37): e4886.
[http://dx.doi.org/10.1097/MD.0000000000004886] [PMID: 27631260]
[65]
WHO HIV 2017.22 Eng | PDF | Cd4 | Hiv/Aids. Scribd Available from: https://www.scribd.com/document/416311426/WHO-HIV-2017-22-eng [cited 2021 Nov 16].
[66]
Ferns RB, Garson JA. Development and evaluation of a real-time rt-pcr assay for quantification of cell-free human immunodeficiency virus type 2 using a brome mosaic virus internal control. J Virol Methods 2006; 135(1): 102-8.
[http://dx.doi.org/10.1016/j.jviromet.2006.02.005] [PMID: 16563526]
[67]
Ariyoshi K, Jaffar S, Alabi AS, et al. Plasma RNA viral load predicts the rate of CD4 T cell decline and death in HIV-2-infected patients in West Africa. AIDS 2000; 14(4): 339-44.
[http://dx.doi.org/10.1097/00002030-200003100-00006] [PMID: 10770535]
[68]
Popper SJ, Sarr AD, Guèye-Ndiaye A, Mboup S, Essex ME, Kanki PJ. Low plasma human immunodeficiency virus type 2 viral load is independent of proviral load: Low virus production in vivo. J Virol 2000; 74(3): 1554-7.
[http://dx.doi.org/10.1128/JVI.74.3.1554-1557.2000] [PMID: 10627569]
[69]
Development of a real-time quantitative RT-PCR for the detection of HIV-2 RNA in plasma. ScienceDirect Available from: https://www.sciencedirect.com/science/article/pii/S0166093400001774?via%3Dihub [cited 2018 Dec 12].
[70]
Soriano V, Gomes P, Heneine W, et al. Human immunodeficiency virus type 2 (HIV-2) in Portugal: Clinical spectrum, circulating subtypes, virus isolation, and plasma viral load. J Med Virol 2000; 61(1): 111-6.
[http://dx.doi.org/10.1002/(SICI)1096-9071(200005)61:1<111:AID-JMV18>3.0.CO;2-W] [PMID: 10745242]
[71]
Ruelle J, Yfantis V, Duquenne A, Goubau P. Validation of an ultrasensitive digital droplet PCR assay for HIV-2 plasma RNA quantification. J Int AIDS Soc 2014; 17(4) (Suppl. 3): 19675. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC 4225411/ [Internet].
[http://dx.doi.org/10.7448/IAS.17.4.19675] [PMID: 25397425]
[72]
Avettand-Fenoel V, Damond F, Gueudin M, et al. New sensitive one-step real-time duplex PCR method for group A and B HIV-2 RNA load. J Clin Microbiol 2014; 52(8): 3017-22.
[http://dx.doi.org/10.1128/JCM.00724-14] [PMID: 24920771]
[73]
Chang M, Gottlieb GS, Dragavon JA, et al. Validation for clinical use of a novel HIV-2 plasma RNA viral load assay using the Abbott m2000 platform. J Clin Virol 2012; 55(2): 128-33.
[http://dx.doi.org/10.1016/j.jcv.2012.06.024] [PMID: 22832059]
[74]
Borrego P, Gonçalves MF, Gomes P, et al. Assessment of the cavidi exavir load assay for monitoring plasma viral load in hiv-2-infected patients. J Clin Microbiol 2017; 55(8): 2367-79.
[http://dx.doi.org/10.1128/JCM.00235-17] [PMID: 28515216]
[75]
Ekouévi DK, Avettand-Fènoël V, Tchounga BK, et al. Plasma HIV-2 RNA according to cd4 count strata among HIV-2-infected adults in the iedea west africa collaboration. PLoS One 2015; 10(6): e0129886.
[http://dx.doi.org/10.1371/journal.pone.0129886] [PMID: 26111242]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy