ORIGINAL RESEARCH Highly Efficient Neutralization by Plasma Antibodies from Human Immunodeficiency Virus Type-1 Infected Individuals on Antiretroviral Drug Therapy Raiees Andrabi & M. A. Makhdoomi & Rajesh Kumar & Manju Bala & Hilal Parray & Arjun Gupta & Ankita Kotnala & Velpandian Thirumurthy & Kalpana Luthra Received: 27 January 2013 /Accepted: 25 February 2014 /Published online: 29 March 2014 # Springer Science+Business Media New York 2014 Abstract Little is known about the neutralizing antibodies induced in HIV-1 patients on antiretroviral treatment, which constitute an interesting group of individuals with improved B cell profile. Plasma samples from 34 HIV-1 seropositive anti- retroviral drug treated (ART) patients were tested for neutral- ization against a panel of 14 subtype-A, B and C tier 1 and tier 2 viruses in TZM-bl assay. Of the 34 plasma samples, remark- ably all the plasma samples were able to neutralize at least one virus while 32 (94 %) were found to neutralize ≥50 % viruses tested. In terms of overall neutralization frequency, approxi- mately 86 %, 68 % and 17 % of the virus/plasma combinations showed 50 % neutralizing activity at 1>60, 1 ≥ 200 and 1 ≥ 2000 dilutions respectively. The improvement in neutralizing activity was shown to be associated with ART in two follow up patients. The neutralization of viruses by two representative plasma samples, AIIMS221 and AIIMS265, was exclusively mediated by immunoglobulin G fractions independent of ART drugs and IgG retained cross-reactive binding to recombinant gp120 proteins. We observed a positive trend of neutralization with duration of ART (p =0.06), however no such correlation was found with clinical and immunological variables like CD4 count (p =0.35), viral load (p =0.09) and plasma total IgG (p = 0.46). Our study suggests that the plasma antibodies from ART patients display high neutralizing activity most likely due to an improved B cell function induced by ART despite low anti- genic stimulation. Keywords HIV-1 . neutralizing antibodies . antiretroviral therapy Electronic supplementary material The online version of this article (doi:10.1007/s10875-014-0010-y) contains supplementary material, which is available to authorized users. J Clin Immunol (2014) 34:504–513 DOI 10.1007/s10875-014-0010-y R. Andrabi : M. A. Makhdoomi : R. Kumar : H. Parray : A. Gupta : K. Luthra (*) Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, India e-mail: kalpanaluthra@gmail.com R. Andrabi e-mail: raieesandrabi@gmail.com M. A. Makhdoomi e-mail: muzamilbiochem@gmail.com R. Kumar e-mail: rajeshkalra84@gmail.com H. Parray e-mail: hilalparray@gmail.com A. Gupta e-mail: guptaarjun90@gmail.com A. Kotnala : V. Thirumurthy Department of Ocular Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi, India A. Kotnala e-mail: k.ankita87@gmail.com V. Thirumurthy e-mail: tvelpandian@gmail.com M. Bala Regional STD Teaching Training & Research Centre, Safdarjang Hospital, New Delhi, India e-mail: manjubala_2@hotmail.com