scholarly journals 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

2006 ◽  
Vol 42 (9) ◽  
pp. 1333-1339 ◽  
Author(s):  
L. Lavreys ◽  
J. M. Baeten ◽  
V. Chohan ◽  
R. S. McClelland ◽  
W. M. Hassan ◽  
...  
2018 ◽  
Author(s):  
Omolara Baiyegunhi ◽  
Bongiwe Ndlovu ◽  
Funsho Ogunshola ◽  
Nasreen Ismail ◽  
Bruce D. Walker ◽  
...  

AbstractDespite decades of focused research, the field has yet to develop a prophylactic vaccine. In the RV144 vaccine trial, non-neutralizing antibody responses were identified as a correlate for prevention of HIV acquisition. However, factors that predict the development of such antibodies are not fully elucidated. We sought to define the contribution of circulating T follicular helper (cTfh) cell subsets to the development of non-neutralizing antibodies in HIV-1 clade C infection. Study participants were recruited from an acute HIV-1 clade C infection cohort. Plasma anti-gp41, -gp120, -p24 and -p17 antibodies were screened using a customized multivariate Luminex assay. Phenotypic and functional characterization of cTfh were performed using HLA class II tetramers and intracellular cytokine staining. In this study, we found that acute HIV-1 clade C infection skewed differentiation of functional cTfh subsets towards increased Tfh1 (p=0.02) and Tfh2 (p<0.0001) subsets, with a concomitant decrease in overall Tfh1-17 (that shares both Tfh1 and Tfh17 properties) (p=0.01) and Tfh17 subsets (p<0.0001) compared to HIV negative subjects. Interestingly, the frequencies of Tfh1 during acute infection (5.0-8.0 weeks post-infection) correlated negatively with set point viral load (p=0.03, r=-60) and were predictive of p24-specific plasma IgG titers at one year of infection (p=0.003, r=0.85). Taken together, our results suggest that circulating the Tfh1 subset plays an important role in the development of anti-HIV antibody responses and contributes to HIV suppression during acute HIV-1 infection. These results have implications for vaccine studies aimed at inducing long lasting anti-HIV antibody responses.ImportanceThe HIV epidemic in southern Africa accounts for almost half of the global HIV burden with HIV-1 clade C being the predominant strain. It is therefore important to define immune correlates of clade C HIV control that might have implications for vaccine design in this region. T follicular helper (Tfh) cells are critical for the development of HIV-specific antibody responses and could play a role in viral control. Here we showed that the early induction of circulating Tfh1 cells during acute infection correlated positively with the magnitude of p24-specific IgG and was associated with lower set point viral load. This study highlights a key Tfh cell subset that could limit HIV replication by enhancing antibody generation. This study underscores the importance of circulating Tfh cells in promoting non-neutralizing antibodies during HIV-1 infection.


2012 ◽  
Vol 205 (2) ◽  
pp. 194-203 ◽  
Author(s):  
Lindi Roberts ◽  
Jo-Ann S. Passmore ◽  
Koleka Mlisana ◽  
Carolyn Williamson ◽  
Francesca Little ◽  
...  

2006 ◽  
Vol 51 (2) ◽  
pp. 566-575 ◽  
Author(s):  
Jeannette M. Whitcomb ◽  
Wei Huang ◽  
Signe Fransen ◽  
Kay Limoli ◽  
Jonathan Toma ◽  
...  

ABSTRACT Most human immunodeficiency virus type 1 (HIV-1) strains require either the CXCR4 or CCR5 chemokine receptor to efficiently enter cells. Blocking viral binding to these coreceptors is an attractive therapeutic target. Currently, several coreceptor antagonists are being evaluated in clinical trials that require characterization of coreceptor tropism for enrollment. In this report, we describe the development of an automated and accurate procedure for determining HIV-1 coreceptor tropism (Trofile) and its validation for routine laboratory testing. HIV-1 pseudoviruses are generated using full-length env genes derived from patient virus populations. Coreceptor tropism is determined by measuring the abilities of these pseudovirus populations to efficiently infect CD4+/U87 cells expressing either the CXCR4 or CCR5 coreceptor. Viruses exclusively and efficiently infecting CXCR4+/CD4+/U87 cells are designated X4-tropic. Conversely, viruses exclusively and efficiently infecting CCR5+/CD4+/U87 cells are designated R5-tropic. Viruses capable of infecting both CXCR4+/CD4+/U87 and CCR5+/CD4+/U87 cells are designated dual/mixed-tropic. Assay accuracy and reproducibility were established by evaluating the tropisms of well-characterized viruses and the variability among replicate results from samples tested repeatedly. The viral subtype, hepatitis B virus or hepatitis C virus coinfection, and the plasma viral load did not affect assay performance. Minority subpopulations with alternate tropisms were reliably detected when present at 5 to 10%. The plasma viral load above which samples can be amplified efficiently in the Trofile assay is 1,000 copies per ml of plasma. Trofile has been automated for high-throughput use; it can be used to identify patients most likely to benefit from treatment regimens that include a coreceptor inhibitor and to monitor patients on treatment for the emergence of resistant virus populations that switch coreceptor tropism.


AIDS ◽  
1998 ◽  
Vol 12 (16) ◽  
pp. 2107-2113 ◽  
Author(s):  
Alfred J. Saah ◽  
Donald R. Hoover ◽  
Shigui Weng ◽  
Mary Carrington ◽  
John Mellors ◽  
...  

2007 ◽  
Vol 23 (10) ◽  
pp. 1242-1250 ◽  
Author(s):  
Gonzalo Bello ◽  
Concepción Casado ◽  
Virginia Sandonis ◽  
Tamara Alvaro-Cifuentes ◽  
Caio A. Rodrigues dos Santos ◽  
...  

2013 ◽  
Vol 29 (1) ◽  
pp. 84-88 ◽  
Author(s):  
John N.S. Gregson ◽  
Leticia Kuri-Cervantes ◽  
Christopher M. Mela ◽  
Brian G. Gazzard ◽  
Mark Bower ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document