Login Register Cart 0
Generic placeholder image

Current HIV Research

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Performance of a Modified In-House HIV-1 Avidity Assay among a Cohort of Newly Diagnosed HIV-1 Infected Individuals and the Effect of ART on the Maturation of HIV-1 Specific Antibodies

Author(s): Diviya Alex, Tennison Inba Raj Williams, Jaiprasath Sachithanandham, Swaminathan Prasannakumar, John Paul Demosthenes, Veena Vadhini Ramalingam, Punitha John Victor, Priscilla Rupali, Gnanadurai John Fletcher and Rajesh Kannangai*

Volume 17, Issue 2, 2019

Page: [134 - 145] Pages: 12

DOI: 10.2174/1570162X17666190712125606

Price: $65

Abstract

Background: Viral kinetics impact humoral immune response to HIV; antibody avidity testing helps distinguish recent (<6 months) and long-term HIV infection. This study aims to determine the frequency of recent HIV-1 infection among clients attending ICTC (Integrated Counselling and Testing Centre) using a commercial EIA, to correlate it with a modified in-house avidity assay and to study the impact of ART on anti-HIV-1 antibody maturation.

Methods: Commercial LAg Avidity EIA was used to detect antibody avidity among 117 treatment naïve HIV-1 infected individuals. A second-generation HIV ELISA was modified for in-house antibody avidity testing and cutoff was set based on Receiver Operating Characteristic (ROC) analysis. Archived paired samples from 25 HIV-1 infected individuals before ART and after successful ART; samples from 7 individuals responding to ART and during virological failure were also tested by LAg Avidity EIA.

Results: Six individuals (5.1%) were identified as recently infected by a combination of LAg avidity assay and HIV-1 viral load testing. The modified in-house avidity assay demonstrated sensitivity and specificity of 100% and 98.2%, respectively, at AI=0.69 by ROC analysis. Median ODn values of individuals when responding to ART were significantly lower than pre-ART [4.136 (IQR 3.437– 4.827) vs 4.455 (IQR 3.748–5.120), p=0.006] whereas ODn values were higher during virological failure [4.260 (IQR 3.665 – 4.515) vs 2.868 (IQR 2.247 – 3.921), p=0.16].

Conclusion: This modified in-house antibody avidity assay is an inexpensive method to detect recent HIV-1 infection. ART demonstrated significant effect on HIV-1 antibody avidity owing to changes in viral kinetics.

Keywords: Avidity assay, LAg avidity assay, HIV, recent infection, ART, India.

« Previous Next »
Graphical Abstract

[1]
World Health Organization. When and how to use assays for recent infection to estimate HIV incidence at a population level 2011.
[2]
Hallett TB. Estimating the HIV incidence rate: recent and future developments. Curr Opin HIV AIDS 2011; 6(2): 102-7.
[http://dx.doi.org/10.1097/COH.0b013e328343bfdb] [PMID: 21505383]
[3]
Busch MP, Pilcher CD, Mastro TD, et al. Beyond detuning: 10 years of progress and new challenges in the development and application of assays for HIV incidence estimation. AIDS 2010; 24(18): 2763-71.
[http://dx.doi.org/10.1097/QAD.0b013e32833f1142] [PMID: 20975514]
[4]
Mastro TD. Determining HIV incidence in populations: moving in the right direction. J Infect Dis 2013; 207(2): 204-6.
[http://dx.doi.org/10.1093/infdis/jis661] [PMID: 23129757]
[5]
UNAIDS Data. 2018.http://www.unaids.org/en/resources/documents/2018/unaids-data-2018
[6]
World Health Organization. World Health Organization global strategy for the surveillance and monitoring of HIV drug resistance 2012.http://apps.who.int/iris/bitstream/10665/77349/1/97892415 04768_eng.pdf
[7]
UNAIDS/WHO. Technical update on HIV incidence assays for surveillance and monitoring purposes 2015.http://www.unaids.org/sites/default/files/media_asset/HIVincidenceassayssurveillancemonitoring_en.pdf
[8]
World Health Organization WHO | HIV drug resistance report. 2017.http://www.who.int/hiv/pub/drugresistance/hivdr-report-2017/en/
[9]
Moyo S, LeCuyer T, Wang R, et al. Evaluation of the false recent classification rates of multiassay algorithms in estimating HIV type 1 subtype C incidence. AIDS Res Hum Retroviruses 2014; 30(1): 29-36.
[http://dx.doi.org/10.1089/aid.2013.0055] [PMID: 23937344]
[10]
Murphy G, Parry JV. Assays for the detection of recent infections with human immunodeficiency virus type 1. Euro Surveill 2008; 13(36): 18966.
[PMID: 18775293]
[11]
Brookmeyer R, Quinn TC. Estimation of current human immunodeficiency virus incidence rates from a cross-sectional survey using early diagnostic tests. Am J Epidemiol 1995; 141(2): 166-72.
[http://dx.doi.org/10.1093/oxfordjournals.aje.a117404] [PMID: 7817972]
[12]
Smoleń-Dzirba J, Wąsik TJ. Current and future assays for identifying recent HIV infections at the population level. Med Sci Monit 2011; 17(5): RA124-33.
[http://dx.doi.org/10.12659/MSM.881757] [PMID: 21525823]
[13]
McDougal JS, Parekh BS, Peterson ML, et al. Comparison of HIV type 1 incidence observed during longitudinal follow-up with incidence estimated by cross-sectional analysis using the BED capture enzyme immunoassay. AIDS Res Hum Retroviruses 2006; 22(10): 945-52.
[http://dx.doi.org/10.1089/aid.2006.22.945] [PMID: 17067263]
[14]
Kim AA, Hallett T, Stover J, et al. Estimating HIV incidence among adults in Kenya and Uganda: a systematic comparison of multiple methods. PLoS One 2011; 6(3): e17535.
[http://dx.doi.org/10.1371/journal.pone.0017535] [PMID: 21408182]
[15]
Parekh BS, Kennedy MS, Dobbs T, et al. Quantitative detection of increasing HIV type 1 antibodies after seroconversion: a simple assay for detecting recent HIV infection and estimating incidence. AIDS Res Hum Retroviruses 2002; 18(4): 295-307.
[http://dx.doi.org/10.1089/088922202753472874] [PMID: 11860677]
[16]
Suligoi B, Galli C, Massi M, et al. Precision and accuracy of a procedure for detecting recent human immunodeficiency virus infections by calculating the antibody avidity index by an automated immunoassay-based method. J Clin Microbiol 2002; 40(11): 4015-20.
[http://dx.doi.org/10.1128/JCM.40.11.4015-4020.2002] [PMID: 12409368]
[17]
Barin F, Meyer L, Lancar R, et al. Development and validation of an immunoassay for identification of recent human immunodeficiency virus type 1 infections and its use on dried serum spots. J Clin Microbiol 2005; 43(9): 4441-7.
[http://dx.doi.org/10.1128/JCM.43.9.4441-4447.2005] [PMID: 16145089]
[18]
Suligoi B, Rodella A, Raimondo M, et al. Avidity Index for anti-HIV antibodies: comparison between third- and fourth-generation automated immunoassays. J Clin Microbiol 2011; 49(7): 2610-3.
[http://dx.doi.org/10.1128/JCM.02115-10] [PMID: 21543577]
[19]
Parekh BS, McDougal JS. New Approaches For Detecting Recent HIV-1 Infection. AIDS Rev 2001; 3: 183-93.
[20]
Janssen RS, Satten GA, Stramer SL, et al. New testing strategy to detect early HIV-1 infection for use in incidence estimates and for clinical and prevention purposes. JAMA 1998; 280(1): 42-8.
[http://dx.doi.org/10.1001/jama.280.1.42] [PMID: 9660362]
[21]
Martró E, Suligoi B, González V, et al. Comparison of the avidity index method and the serologic testing algorithm for recent Human Immunodeficiency Virus (HIV) seroconversion, two methods using a single serum sample for identification of recent HIV infections. J Clin Microbiol 2005; 43(12): 6197-9.
[http://dx.doi.org/10.1128/JCM.43.12.6197-6199.2005] [PMID: 16333129]
[22]
Gao Z, Yan H, Feng X, et al. Development of a new limiting-antigen avidity dot immuno-gold filtration assay for HIV-1 incidence. PLoS One 2016; 11(8): e0161183.
[http://dx.doi.org/10.1371/journal.pone.0161183] [PMID: 27513563]
[23]
Hauser A, Santos-Hoevener C, Meixenberger K, et al. Improved testing of recent HIV-1 infections with the BioRad avidity assay compared to the limiting antigen avidity assay and BED Capture enzyme immunoassay: evaluation using reference sample panels from the German Seroconverter Cohort. PLoS One 2014; 9(6): e98038.
[http://dx.doi.org/10.1371/journal.pone.0098038] [PMID: 24892795]
[24]
Thomas HI, Wilson S, O’Toole CM, et al. Differential maturation of avidity of IgG antibodies to gp41, p24 and p17 following infection with HIV-1. Clin Exp Immunol 1996; 103(2): 185-91.
[http://dx.doi.org/10.1046/j.1365-2249.1996.951642.x] [PMID: 8565298]
[25]
Curtis KA, Kennedy MS, Charurat M, et al. Development and characterization of a bead-based, multiplex assay for estimation of recent HIV type 1 infection. AIDS Res Hum Retroviruses 2012; 28(2): 188-97.
[http://dx.doi.org/10.1089/aid.2011.0037] [PMID: 21585287]
[26]
Wei X, Liu X, Dobbs T, et al. Development of two avidity-based assays to detect recent HIV type 1 seroconversion using a multisubtype gp41 recombinant protein. AIDS Res Hum Retroviruses 2010; 26(1): 61-71.
[http://dx.doi.org/10.1089/aid.2009.0133] [PMID: 20063992]
[27]
Suligoi B, Massi M, Galli C, et al. Identifying recent HIV infections using the avidity index and an automated enzyme immunoassay. J Acquir Immune Defic Syndr 2003; 32(4): 424-8.
[http://dx.doi.org/10.1097/00126334-200304010-00012] [PMID: 12640201]
[28]
Chawla A, Murphy G, Donnelly C, et al. Human immunodeficiency virus (HIV) antibody avidity testing to identify recent infection in newly diagnosed HIV type 1 (HIV-1)-seropositive persons infected with diverse HIV-1 subtypes. J Clin Microbiol 2007; 45(2): 415-20.
[http://dx.doi.org/10.1128/JCM.01879-06] [PMID: 17151211]
[29]
Re MC, Schiavone P, Bon I, et al. Incomplete IgG response to HIV-1 proteins and low avidity levels in recently converted HIV patients treated with early antiretroviral therapy. Int J Infect Dis 2010; 14(11): e1008-12.
[http://dx.doi.org/10.1016/j.ijid.2010.06.015] [PMID: 20869896]
[30]
Wendel SK, Mullis CE, Eshleman SH, et al. Effect of natural and ARV-induced viral suppression and viral breakthrough on anti-HIV antibody proportion and avidity in patients with HIV-1 subtype B infection. PLoS One 2013; 8(2): e55525.
[http://dx.doi.org/10.1371/journal.pone.0055525] [PMID: 23437058]
[31]
National AIDS Control Organisation, Ministry of Health & Family Welfare, Government of India. National Guidelines for HIV Testing. 2015.http://www.naco.gov.in/sites/default/files/National_ Guidelines_for_HIV_Testing_21Apr2016.pdf
[32]
Laeyendecker O, Gray RH, Grabowski MK, et al. Validation of the limiting antigen avidity assay to estimate level and trends in HIV incidence in an A/D epidemic in Rakai, Uganda. AIDS Res Hum Retroviruses 2019; 35(4): 364-7.
[http://dx.doi.org/10.1089/aid.2018.0207] [PMID: 30560723]
[33]
Duong YT, Qiu M, De AK, et al. Detection of recent HIV-1 infection using a new limiting-antigen avidity assay: potential for HIV-1 incidence estimates and avidity maturation studies. PLoS One 2012; 7(3): e33328.
[http://dx.doi.org/10.1371/journal.pone.0033328] [PMID: 22479384]
[34]
Laeyendecker O, Konikoff J, Morrison DE, et al. Identification and validation of a multi-assay algorithm for cross-sectional HIV incidence estimation in populations with subtype C infection. J Int AIDS Soc 2018; 21(2): 21.
[http://dx.doi.org/10.1002/jia2.25082] [PMID: 29489059]
[35]
Konikoff J, Brookmeyer R, Longosz AF, et al. Performance of a limiting-antigen avidity enzyme immunoassay for cross-sectional estimation of HIV incidence in the United States. PLoS One 2013; 8(12): e82772.
[http://dx.doi.org/10.1371/journal.pone.0082772] [PMID: 24386116]
[36]
Duong YT, Kassanjee R, Welte A, et al. Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes. PLoS One 2015; 10(2): e0114947.
[http://dx.doi.org/10.1371/journal.pone.0114947] [PMID: 25710171]
[37]
Kassanjee R, Pilcher CD, Keating SM, et al. Independent assessment of candidate HIV incidence assays on specimens in the CEPHIA repository. AIDS 2014; 28(16): 2439-49.
[http://dx.doi.org/10.1097/QAD.0000000000000429] [PMID: 25144218]
[38]
Mani M, Ramalingam VV, Lionel J, et al. Emergence of HIV-1 drug-resistant variants in women following antiretroviral prophylaxis for the prevention of mother to child transmission. Indian J Med Microbiol 2015; 33(2): 225-30.
[http://dx.doi.org/10.4103/0255-0857.154860] [PMID: 25865972]
[39]
Truong HM, Fatch R, Grant RM, et al. Characterization of HIV recent infection among high-risk men at public STI clinics in Mumbai. AIDS Behav 2018; 22(Suppl. 1): 70-5.
[http://dx.doi.org/10.1007/s10461-018-2052-2] [PMID: 29453551]
[40]
Solomon SS, Celentano DD, Srikrishnan AK, et al. Low incidences of human immunodeficiency virus and hepatitis C virus infection and declining risk behaviors in a cohort of injection drug users in Chennai, India. Am J Epidemiol 2010; 172(11): 1259-67.
[http://dx.doi.org/10.1093/aje/kwq288] [PMID: 20935070]
[41]
Wawer MJ, Gray RH, Sewankambo NK, et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis 2005; 191(9): 1403-9.
[http://dx.doi.org/10.1086/429411] [PMID: 15809897]
[42]
Hollingsworth TD, Anderson RM, Fraser C. HIV-1 transmission, by stage of infection. J Infect Dis 2008; 198(5): 687-93.
[http://dx.doi.org/10.1086/590501] [PMID: 18662132]
[43]
Anderson RM, May RM. Epidemiological parameters of HIV transmission. Nature 1988; 333(6173): 514-9.
[http://dx.doi.org/10.1038/333514a0] [PMID: 3374601]
[44]
Leynaert B, Downs AM, de Vincenzi I. Heterosexual transmission of human immunodeficiency virus: variability of infectivity throughout the course of infection. Am J Epidemiol 1998; 148(1): 88-96.
[http://dx.doi.org/10.1093/oxfordjournals.aje.a009564] [PMID: 9663408]
[45]
Marks G, Crepaz N, Senterfitt JW, Janssen RS. Meta-analysis of high-risk sexual behavior in persons aware and unaware they are infected with HIV in the United States: implications for HIV prevention programs. J Acquir Immune Defic Syndr 2005; 39(4): 446-53.
[http://dx.doi.org/10.1097/01.qai.0000151079.33935.79] [PMID: 16010168]
[46]
Marks G, Crepaz N, Janssen RS. Estimating sexual transmission of HIV from persons aware and unaware that they are infected with the virus in the USA. AIDS 2006; 20(10): 1447-50.
[http://dx.doi.org/10.1097/01.aids.0000233579.79714.8d] [PMID: 16791020]
[47]
Colfax GN, Buchbinder SP, Cornelisse PGA, Vittinghoff E, Mayer K, Celum C. Sexual risk behaviors and implications for secondary HIV transmission during and after HIV seroconversion. AIDS 2002; 16(11): 1529-35.
[http://dx.doi.org/10.1097/00002030-200207260-00010] [PMID: 12131191]
[48]
Moyo S, Kotokwe KP, Mohammed T, et al. Low false recent rate of limiting antigen-avidity assay combined with HIV-1 RNA data in Botswana. AIDS Res Hum Retroviruses 2016; 33(1): 17-8.
[PMID: 27481530]
[49]
Keating SM, Hanson D, Lebedeva M, et al. Lower-sensitivity and avidity modifications of the vitros anti-HIV 1+2 assay for detection of recent HIV infections and incidence estimation. J Clin Microbiol 2012; 50(12): 3968-76.
[http://dx.doi.org/10.1128/JCM.01454-12] [PMID: 23035182]
[50]
Masciotra S, Dobbs T, Candal D, et al. Antibody avidity-based assay for identifying recent HIV-1 infections Based on Genetic Systems [TM] 1/2 Plus O EIA [#937 17th Conf Retroviruses Opportunistic Infect. San Francisco, CA. 2010.
[51]
Kassanjee R, Pilcher CD, Busch MP, et al. Viral load criteria and threshold optimization to improve HIV incidence assay characteristics. AIDS 2016; 30(15): 2361-71.
[http://dx.doi.org/10.1097/QAD.0000000000001209] [PMID: 27454561]
[52]
Kandathil AJ, Ramalingam S, Kannangai R, David S, Sridharan G. Molecular epidemiology of HIV. Indian J Med Res 2005; 121(4): 333-44.
[PMID: 15817947]
[53]
Neogi U, Bontell I, Shet A, et al. Molecular epidemiology of HIV-1 subtypes in India: Origin and evolutionary history of the predominant subtype C. PLoS One 2012; 7(6): e39819.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387228/
[PMID: 22768132]
[54]
Sahni AK, Prasad VVSP, Seth P. Genomic diversity of human immunodeficiency virus type-1 in India. Int J STD AIDS 2002; 13(2): 115-8.
[http://dx.doi.org/10.1258/0956462021924749] [PMID: 11839166]
[55]
Gadkari DA, Moore D, Sheppard HW, Kulkarni SS, Mehendale SM, Bollinger RC. Transmission of genetically diverse strains of HIV-1 in Pune, India. Indian J Med Res 1998; 107: 1-9.
[PMID: 9529774]
[56]
Mandal D, Jana S, Panda S, et al. Distribution of HIV-1 subtypes in female sex workers of Calcutta, India. Indian J Med Res 2000; 112: 165-72.
[PMID: 12452124]
[57]
Ramalingam S, Kannangai R, Vijayakumar TS, et al. Subtype & cytokine profiles of HIV infected individuals from south India. Indian J Med Res 2005; 121(4): 226-34.
[PMID: 15817940]
[58]
Jameel S, Zafrullah M, Ahmad M, Kapoor GS, Sehgal S. A genetic analysis of HIV-1 from Punjab, India reveals the presence of multiple variants. AIDS 1995; 9(7): 685-90.
[http://dx.doi.org/10.1097/00002030-199507000-00003] [PMID: 7546411]
[59]
Shen C, Craigo J, Ding M, Chen Y, Gupta P. Origin and dynamics of HIV-1 subtype C infection in India. PLoS One 2011; 6(10): e25956.
[http://dx.doi.org/10.1371/journal.pone.0025956] [PMID: 22016790]
[60]
Rodriguez MA, Ding M, Ratner D, et al. High replication fitness and transmission efficiency of HIV-1 subtype C from India: Implications for subtype C predominance. Virology 2009; 385(2): 416-24.
[http://dx.doi.org/10.1016/j.virol.2008.12.025] [PMID: 19157481]
[61]
Shepherd SJ, McAllister G, Kean J, et al. Development of an avidity assay for detection of recent HIV infections. J Virol Methods 2015; 217: 42-9.
[http://dx.doi.org/10.1016/j.jviromet.2015.02.016] [PMID: 25721468]
[62]
Moore JP, Cao Y, Ho DD, Koup RA. Development of the anti-gp120 antibody response during seroconversion to human immunodeficiency virus type 1. J Virol 1994; 68(8): 5142-55.
[PMID: 8035514]
[63]
Parekh BS, Pau CP, Kennedy MS, Dobbs TL, McDougal JS. Assessment of antibody assays for identifying and distinguishing recent from long-term HIV type 1 infection. AIDS Res Hum Retroviruses 2001; 17(2): 137-46.
[http://dx.doi.org/10.1089/08892220150217229] [PMID: 11177393]
[64]
Selleri M, Orchi N, Zaniratti MS, et al. Effective highly active antiretroviral therapy in patients with primary HIV-1 infection prevents the evolution of the avidity of HIV-1-specific antibodies. J Acquir Immune Defic Syndr 2007; 46(2): 145-50.
[http://dx.doi.org/10.1097/QAI.0b013e318120039b] [PMID: 17589369]
[65]
Altfeld M, Rosenberg ES, Shankarappa R, et al. Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection. J Exp Med 2001; 193(2): 169-80.
[http://dx.doi.org/10.1084/jem.193.2.169] [PMID: 11148221]
[66]
Smith D, Berrey MM, Robertson M, et al. Virological and immunological effects of combination antiretroviral therapy with zidovudine, lamivudine, and indinavir during primary human immunodeficiency virus type 1 infection. J Infect Dis 2000; 182(3): 950-4.
[http://dx.doi.org/10.1086/315753] [PMID: 10950796]
[67]
Adalid-Peralta L, Grangeot-Keros L, Rudent A, et al. Impact of highly active antiretroviral therapy on the maturation of anti-HIV-1 antibodies during primary HIV-1 infection. HIV Med 2006; 7(8): 514-9.
[http://dx.doi.org/10.1111/j.1468-1293.2006.00406.x] [PMID: 17105510]
[68]
Kassutto S, Johnston MN, Rosenberg ES. Incomplete HIV type 1 antibody evolution and seroreversion in acutely infected individuals treated with early antiretroviral therapy. Clin Infect Dis 2005; 40(6): 868-73.
[http://dx.doi.org/10.1086/428127] [PMID: 15736021]
[69]
Hare CB, Pappalardo BL, Busch MP, et al. Seroreversion in subjects receiving antiretroviral therapy during acute/early HIV infection. Clin Infect Dis 2006; 42(5): 700-8.
[http://dx.doi.org/10.1086/500215] [PMID: 16447118]
[70]
Le Guillou-Guillemette H, Renier G, Vielle B, et al. Immune restoration under HAART in patients chronically infected with HIV-1: diversity of T, B, and NK immune responses. Viral Immunol 2006; 19(2): 267-76.
[http://dx.doi.org/10.1089/vim.2006.19.267] [PMID: 16817769]
[71]
Maartens G, Celum C, Lewin SR. HIV infection: epidemiology, pathogenesis, treatment, and prevention. Lancet 2014; 384(9939): 258-71.
[http://dx.doi.org/10.1016/S0140-6736(14)60164-1] [PMID: 24907868]
[72]
Hayashida T, Gatanaga H, Tanuma J, Oka S. Effects of low HIV type 1 load and antiretroviral treatment on IgG-capture BED-enzyme immunoassay. AIDS Res Hum Retroviruses 2008; 24(3): 495-8.
[http://dx.doi.org/10.1089/aid.2007.0150] [PMID: 18327979]
[73]
Markowitz M, Vesanen M, Tenner-Racz K, et al. The effect of commencing combination antiretroviral therapy soon after human immunodeficiency virus type 1 infection on viral replication and antiviral immune responses. J Infect Dis 1999; 179(3): 527-37.
[http://dx.doi.org/10.1086/314628] [PMID: 9952358]
[74]
Binley JM, Trkola A, Ketas T, et al. The effect of highly active antiretroviral therapy on binding and neutralizing antibody responses to human immunodeficiency virus type 1 infection. J Infect Dis 2000; 182(3): 945-9.
[http://dx.doi.org/10.1086/315774] [PMID: 10950795]
[75]
Rosenberg ES, Altfeld M, Poon SH, et al. Immune control of HIV-1 after early treatment of acute infection. Nature 2000; 407(6803): 523-6.
[http://dx.doi.org/10.1038/35035103] [PMID: 11029005]
[76]
Kaufmann GR, Bloch M, Zaunders JJ, Smith D, Cooper DA. Long-term immunological response in HIV-1-infected subjects receiving potent antiretroviral therapy. AIDS 2000; 14(8): 959-69.
[http://dx.doi.org/10.1097/00002030-200005260-00007] [PMID: 10853977]
[77]
Lacabaratz-Porret C, Urrutia A, Doisne J-M, et al. Impact of antiretroviral therapy and changes in virus load on human immunodeficiency virus (HIV)-specific T cell responses in primary HIV infection. J Infect Dis 2003; 187(5): 748-57.
[http://dx.doi.org/10.1086/368333] [PMID: 12599048]
[78]
Orrell C, Kaplan R, Wood R, Bekker LG. Virological breakthrough: a risk factor for loss to followup in a large community-based cohort on antiretroviral therapy. Aids Res Treat 2011; 2011: 469127.
[http://dx.doi.org/10.1155/2011/469127] [PMID: 21716724]

Rights & Permissions Print Cite
Article Metrics
32
3
© 2024 Bentham Science Publishers | Privacy Policy