The sensitivity of an HIV P24 antigen and antibody assay used in paralel (3rd Generation) compared to HIV antigen/antibody combination assays (4th generation) to detect recent HIV infection in South African blood donors as identified through nucleic acid

Abstract: Introduction Although Nucleic Acid Testing has become the gold standard for the detection of HIV it remains an expensive technology. In Africa the use of sensitive serological assays might be a more viable option. HIV Combo assays have been on the market for several years and have been evaluated. Four cases of a 2nd diagnostic window period have been reported by the use of these assays. This raised questions regarding the sensitivity of these Combo assays compared to stand-alone serological assays for HIV detecting antigen and antibodies separately. In this study the sensitivity of three HIV Combo assays were compared to stand-alone assays by the use of 2 unique sample groups of early HIV infections as identified by NAT since 2005 by the South African National Blood Service (SANBS). Methods A retrospective study using two sample groups of archived plasma from HIV positive blood donors; A) 153 HIV NAT yield samples B) 87 low antibody ratio (Abbott Prism) recent HIV samples. These groups were tested by three HIV Combo assays (Abbott, Biorad and Roche) and one p24 antigen assay (Innogenetics). The Abbott Prism HIV O Plus assay results were already available as reference method for antibody detection. Sensitivity to detect HIV antigen and/or antibodies were evaluated. The significance of donor demographic indicators of donor group (new, re-joined or active) race, age, gender and region were analysed in relation to the presence/absence of p24 antigen between the two groups..

Cost-effectiveness analysis of introducing HTLV-1 testing in South Africa

We have previously reported a 2013 cross-sectional study of HTLV prevalence among 46,765 South African blood donors. Confirmed HTLV-1 prevalence was 0.16% in Black donors, 0.02% in both White and Coloured donors and 0% in south Asian donors, for an overall prevalence of 0.062% extrapolated to the current blood donor population. Using these data we estimated the cost effectiveness of potential HTLV screening strategies in preventing transfusion transmitted HTLV-1 infection (TTI). Five blood donor screening strategies were considered: no screening; HTLV testing of every donation; HTLV testing each donor one time only; HTLV testing of new donors only; and universal filter leukodepletion without HTLV testing

Transmitted/Founder and Chronic Subtype C HIV-1 Use CD4 and CCR5 Receptors with Equal Efficiency and Are Not Inhibited by Blocking the Integrin α4β7

Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells and some encode envelope glycoproteins (Envs) that contain fewer potential N-linked glycosylation sites and shorter V1/V2 variable loops than Envs from chronic viruses. Moreover, it has been reported that the gp120 subunits of certain transmitted Envs bind to the gut-homing integrin α4β7, possibly enhancing virus entry and cell-to-cell spread. Here we sought to determine whether subtype C T/F viruses, which are responsible for the majority of new HIV-1 infections worldwide, share biological properties that increase their transmission fitness, including preferential α4β7 engagement. Using single genome amplification, we generated panels of both T/F (n = 20) and chronic (n = 20) Env constructs as well as full-length T/F (n = 6) and chronic (n = 4) infectious molecular clones (IMCs). We found that T/F and chronic control Envs were indistinguishable in the efficiency with which they used CD4 and CCR5. Both groups of Envs also exhibited the same CD4+ T cell subset tropism and showed similar sensitivity to neutralization by CD4 binding site (CD4bs) antibodies. Finally, saturating concentrations of anti-α4β7 antibodies failed to inhibit infection and replication of T/F as well as chronic control viruses, although the growth of the tissue culture-adapted strain SF162 was modestly impaired. These results indicate that the population bottleneck associated with mucosal HIV-1 acquisition is not due to the selection of T/F viruses that use α4β7, CD4 or CCR5 more efficiently

The sensitivity of HIV P24 and HIV antigen/antibody combination (4th Generation) assays to detect recently infected donors identified over a five year period (2005-2010) in South African Blood Donors

M.Tech. (Biomedical Technology)Abstract: Please refer to full text to view abstrac

The prevalence of human T‐lymphotropic virus type 1 & 2 (HTLV‐1/2) in South African blood donors

International audienceBackground and objectivesDonated blood is not currently screened for human T‐cell lymphotropic virus (HTLV) in South Africa. Several small studies have detected HTLV‐1 in South Africa, but prevalence by geographic region or population group is unavailable.Materials and MethodsWe performed a large seroprevalence study of South African blood donors during 3 months in 2013. All geographic regions except the Western Cape were included, and Black and Coloured (local term for mixed race) donors were oversampled. Identity‐unlinked plasma samples were screened with the Abbott Prism HTLV‐1/2 assay, and repeatedly reactive samples were tested by the Inno‐LIA HTLV‐1/2 Score confirmatory assay. Odds ratios were calculated with multivariable logistic regression.ResultsOf 46 752 donors tested, 133 (0·28%) were initially reactive, 111 (0·24%) repeatedly reactive and 57 (0·12%) confirmed positive for HTLV‐1; none were HTLV‐2 positive. Prevalence was 0·062% weighted to annual blood donations but highly concentrated in the Black population group (OR = 20·24 CI: 2·77–147·88); higher in females than males (OR = 1·81 CI: 1·06–3·08); and in donors aged >50 years compared to ages 16–19 (OR = 6·4 CI: 2·95‐13·86). After controlling for age, sex and population group, there was no difference in prevalence between new and repeat blood donors or among geographic regions within South Africa.ConclusionsWe conclude that HTLV‐1 infection is widespread among the Black population of South Africa and its epidemiology is similar to other endemic areas. Because South Africa is increasing its recruitment of Black blood donors, the implications for blood screening require further consideration

Blocking α4β7 inhibits replication of NL4-3-SF162 and NL4-3-R3A but not YU-2.

<p>CD4+ T cells with or without Act1 pre-treatment were infected at three different multiplicities using CD4+ T cell derived virus stock (1 µl, 10 µl and 100 µl) to initiate a spreading infection. Infections were performed in six replicate wells, each of which was sampled at days three, six and nine. (<b>A-C</b>) Virus production at day six as measured by p24 content in culture supernatants is shown on the y-axis for each of six replicate wells from one of three independent experiments; uncorrected Mann-Whitney <i>p</i> values are shown for comparisons of no antibody (solid symbols) versus Act1-treated (open symbols) replicate wells (bar = mean). (<b>D</b>) Replication kinetics are shown for NL4-3-SF162 (mean of replicates ± SEM is presented) at three different multiplicities of infection. Inhibition of infection was transient and greatest at six days post infection at the lowest viral input; uncorrected Mann-Whitney p-values less than 0.05 comparing no mAb to Act1 are marked by asterisks.</p