scholarly journals Construction of a High Titer Infectious HIV-1 Subtype C Proviral Clone from South Africa

Viruses ◽  
2012 ◽  
Vol 4 (9) ◽  
pp. 1830-1843 ◽  
Author(s):  
Graeme B. Jacobs ◽  
Stefanie Bock ◽  
Anita Schuch ◽  
Rebecca Moschall ◽  
Eva-Maria Schrom ◽  
...  
Keyword(s):  
South Africa ◽  
High Titer ◽  
Subtype C ◽  
Proviral Clone ◽  
Hiv 1

Full-Length Genome Analysis of HIV-1 Subtype C Utilizing CXCR4 and Intersubtype Recombinants Isolated in South Africa

2002 ◽  
Vol 18 (12) ◽  
pp. 879-886 ◽  
Author(s):  
Maria A. Papathanasopoulos ◽  
Tonie Cilliers ◽  
Lynn Morris ◽  
John L. Mokili ◽  
William Dowling ◽  
...  
Keyword(s):  
South Africa ◽  
Genome Analysis ◽  
Full Length ◽  
Subtype C ◽  
Full Length Genome ◽  
Hiv 1

scholarly journals HIV-1 Subtype C-Infected Children with Exceptional Neutralization Breadth Exhibit Polyclonal Responses Targeting Known Epitopes

2018 ◽  
Vol 92 (17) ◽  
Author(s):  
Zanele Ditse ◽  
Maximilian Muenchhoff ◽  
Emily Adland ◽  
Pieter Jooste ◽  
Philip Goulder ◽  
...  
Keyword(s):  
Immune System ◽  
Neutralizing Antibodies ◽  
High Titer ◽  
Neutralizing Antibody ◽  
Subtype C ◽  
Child Pair ◽  
Intact Immune System ◽  
Antibody Specificities ◽  
Hiv Envelope ◽  
Hiv 1

ABSTRACT We have previously shown that HIV-1-infected children develop broader and more potent neutralizing antibody responses than adults. This study aimed to determine the antibody specificities in 16 HIV-1 subtype C-infected children who displayed exceptional neutralization breadth on a 22-multisubtype virus panel. All children were antiretroviral treatment (ART) naive with normal CD4 counts despite being infected for a median of 10.1 years with high viral loads. The specificity of broadly neutralizing antibodies (bNAbs) was determined using epitope-ablating mutants, chimeric constructs, and depletion or inhibition of activity with peptides and glycoproteins. We found that bNAbs in children largely targeted previously defined epitopes, including the V2-glycan, V3-glycan, CD4bs, and gp120-gp41 interface. Remarkably, 63% of children had antibodies targeting 2 or 3 and, in one case, 4 of these bNAb epitopes. Longitudinal analysis of plasma from a mother-child pair over 9 years showed that while they both had similar neutralization profiles, the antibody specificities differed. The mother developed antibodies targeting the V2-glycan and CD4bs, whereas bNAb specificities in the child could not be mapped until 6 years, when a minor V2-glycan response appeared. The child also developed high-titer membrane-proximal external region (MPER) binding antibodies not seen in the mother, although these were not a major bNAb specificity. Overall, exceptional neutralization breadth in this group of children may be the result of extended exposure to high antigenic load in the context of an intact immune system, which allowed for the activation of multiple B cell lineages and the generation of polyclonal responses targeting several bNAb epitopes. IMPORTANCE An HIV vaccine is likely to require bNAbs, which have been shown to prevent HIV acquisition in nonhuman primates. Recent evidence suggests that HIV-infected children are inherently better at generating bNAbs than adults. Here, we show that exceptional neutralization breadth in a group of viremic HIV-1 subtype C-infected children was due to the presence of polyclonal bNAb responses. These bNAbs targeted multiple epitopes on the HIV envelope glycoprotein previously defined in adult infection, suggesting that the immature immune system recognizes HIV antigens similarly. Since elicitation of a polyclonal bNAb response is the basis of next-generation HIV envelope vaccines, further studies of how bNAb lineages are stimulated in children is warranted. Furthermore, our findings suggest that children may respond particularly well to vaccines designed to elicit antibodies to multiple bNAb epitopes.

Molecular Genetics and the Incidence of Transmitted Drug Resistance Among Pre-Treatment HIV-1 Infected Patients in the Eastern Cape, South Africa

2019 ◽  
Vol 17 (5) ◽  
pp. 335-342
Author(s):  
Tennison Onoriode Digban ◽  
Benson Chucks Iweriebor ◽  
Larry Chikwelu Obi ◽  
Uchechuwku Nwodo ◽  
Anthony Ifeanyi Okoh
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Transmitted Drug Resistance ◽  
Eastern Cape ◽  
Resistance Mutations ◽  
Subtype C ◽  
Drug Resistance Mutations ◽  
Combined Antiretroviral Therapy ◽  
Pre Treatment ◽  
Hiv 1

Background: Transmitted drug resistance (TDR) remains a significant threat to Human immunodeficiency virus (HIV) infected patients that are not exposed to antiretroviral treatment. Although, combined antiretroviral therapy (cART) has reduced deaths among infected individuals, emergence of drug resistance is gradually on rise. Objective: To determine the drug resistance mutations and subtypes of HIV-1 among pre-treatment patients in the Eastern Cape of South Africa. Methods: Viral RNA was extracted from blood samples of 70 pre-treatment HIV-1 patients while partial pol gene fragment amplification was achieved with specific primers by RT-PCR followed by nested PCR and positive amplicons were sequenced utilizing ABI Prism 316 genetic sequencer. Drug resistance mutations (DRMs) analysis was performed by submitting the generated sequences to Stanford HIV drug resistance database. Results: Viral DNA was successful for 66 (94.3%) samples of which 52 edited sequences were obtained from the protease and 44 reverse transcriptase sequences were also fully edited. Four major protease inhibitor (PI) related mutations (I54V, V82A/L, L76V and L90M) were observed in seven patients while several other minor and accessory PIs were also identified. A total of 11(25.0%) patients had NRTIs related mutations while NNRTIs were observed among 14(31.8%) patients. K103N/S, V106M and M184V were the most common mutations identified among the viral sequences. Phylogenetic analysis of the partial pol gene indicated all sequences clustered with subtype C. Conclusions: This study indicates that HIV-1 subtype C still predominates and responsible for driving the epidemic in the Eastern Cape of South Africa with slow rise in the occurrence of transmitted drug resistance.

scholarly journals High Prevalence of the K65R Mutation in HIV-1 Subtype C Infected Patients Failing Tenofovir-Based First-Line Regimens in South Africa

PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0118145 ◽  
Author(s):  
Lindiwe Skhosana ◽  
Kim Steegen ◽  
Michelle Bronze ◽  
Azwidowi Lukhwareni ◽  
Esrom Letsoalo ◽  
...  
Keyword(s):  
South Africa ◽  
Subtype C ◽  
First Line ◽  
K65r Mutation ◽  
High Prevalence ◽  
Hiv 1

scholarly journals High level of HIV-2 false positivity in KwaZulu-Natal province: A region of South Africa with a very high HIV-1 subtype C prevalence

2013 ◽  
Vol 85 (12) ◽  
pp. 2065-2071 ◽  
Author(s):  
Lavanya Singh ◽  
Raveen Parboosing ◽  
Justen Manasa ◽  
Pravi Moodley ◽  
Tulio de Oliveira
Keyword(s):  
South Africa ◽  
Subtype C ◽  
False Positivity ◽  
Kwazulu Natal ◽  
High Level ◽  
Very High ◽  
Hiv 1

scholarly journals Protease Inhibitor Resistance Is Uncommon in HIV-1 Subtype C Infected Patients on Failing Second-Line Lopinavir/r-Containing Antiretroviral Therapy in South Africa

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Carole L. Wallis ◽  
John W. Mellors ◽  
Willem D. F. Venter ◽  
Ian Sanne ◽  
Wendy Stevens
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Protease Inhibitor ◽  
Virologic Failure ◽  
Second Line ◽  
Resistance Mutations ◽  
Subtype C ◽  
Resistance Patterns ◽  
Main Barrier ◽  
Hiv 1

Limited data exist on HIV-1 drug resistance patterns in South Africa following second-line protease-inhibitor containing regimen failure. This study examined drug resistance patterns emerging in 75 HIV-1 infected adults experiencing virologic failure on a second-line regimen containing 2 NRTI and lopinavir/ritonavir. Ninety six percent of patients (n=72) were infected with HIV-1 subtype C, two patients were infected with HIV-1 subtype D and one with HIV-1 subtype A1. Thirty nine percent (n=29) of patients had no resistance mutations in protease or reverse transcriptase suggesting that medication non-adherence was a major factor contributing to failure. Major lopinavir resistance mutations were infrequent (5 of 75; 7%), indicating that drug resistance is not the main barrier to future viral suppression.

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