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HIV Seropositivity: HELP
Articles by Lynn Morris
Based on 6 articles published since 2010
(Why 6 articles?)
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Between 2010 and 2020, Lynn Morris wrote the following 6 articles about HIV Seropositivity.
 
+ Citations + Abstracts
1 Clinical Trial Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants. 2016

Churchyard, Gavin / Mlisana, Koleka / Karuna, Shelly / Williamson, Anna-Lise / Williamson, Carolyn / Morris, Lynn / Tomaras, Georgia D / De Rosa, Stephen C / Gilbert, Peter B / Gu, Niya / Yu, Chenchen / Mkhize, Nonhlanhla N / Hermanus, Tandile / Allen, Mary / Pensiero, Michael / Barnett, Susan W / Gray, Glenda / Bekker, Linda-Gail / Montefiori, David C / Kublin, James / Corey, Lawrence. ·Aurum Institute for Health Research, Klerksdorp, South Africa. · School of Public Health, University of Witwatersrand, Johannesburg, South Africa. · Advancing Care and Treatment for TB and HIV, Medical Research Council Collaborating Centre, Klerksdorp, South Africa. · University of Kwa-Zulu Natal, Durban, South Africa. · Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America. · Institute of Infectious Disease and Molecular Medicine, Division of Medical Virology, University of Cape Town, Cape Town, South Africa; National Health Laboratory Services, Observatory, Cape Town, South Africa. · National Institute for Communicable Diseases, National Health Laboratory Services, Sandringham, Johannesburg, South Africa. · Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America. · Department of Laboratory Medicine, University of Washington, Seattle, WA, United States of America. · Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America. · Novartis Vaccines and Diagnostics, Cambridge, MA, United States of America. · South African Medical Research Council, Cape Town, South Africa. · Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Braamfontein, Johannesburg, South Africa. · Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. · Laboratory for AIDS Vaccine Research and Development, Duke University Medical Center, Durham, NC, United States of America. ·PLoS One · Pubmed #27583368.

ABSTRACT: BACKGROUND: The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM), SAAVI MVA-C (2.9 x 109 pfu IM) and Novartis V2-deleted subtype C gp140 (100 mcg) with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa. METHODS: Participants at three South African sites were randomized (1:1:1:1) to one of four vaccine regimens: MVA prime, sequential gp140 protein boost (M/M/P/P); concurrent MVA/gp140 (MP/MP); DNA prime, sequential MVA boost (D/D/M/M); DNA prime, concurrent MVA/gp140 boost (D/D/MP/MP) or placebo. Peak HIV specific humoral and cellular responses were measured. RESULTS: 184 participants were enrolled: 52% were female, all were Black/African, median age was 23 years (range, 18-42 years) and 79% completed all vaccinations. 159 participants reported at least one adverse event, 92.5% were mild or moderate. Five, unrelated, serious adverse events were reported. The M/M/P/P and D/D/MP/MP regimens induced the strongest peak neutralizing and binding antibody responses and the greatest CD4+ T-cell responses to Env. All peak neutralizing and binding antibody responses decayed with time. The MVA, but not DNA, prime contributed to the humoral and cellular immune responses. The D/D/M/M regimen was poorly immunogenic overall but did induce modest CD4+ T-cell responses to Gag and Pol. CD8+ T-cell responses to any antigen were low for all regimens. CONCLUSIONS: The SAAVI DNA-C2, SAAVI MVA-C and Novartis gp140 with MF59 adjuvant in various combinations were safe and induced neutralizing and binding antibodies and cellular immune responses. Sequential immunization with gp140 boosted immune responses primed by MVA or DNA. The best overall immune responses were seen with the M/M/P/P regimen. TRIAL REGISTRATION: ClinicalTrials.gov NCT01418235.

2 Clinical Trial Reactivity of routine HIV antibody tests in children who initiated antiretroviral therapy in early infancy as part of the Children with HIV Early Antiretroviral Therapy (CHER) trial: a retrospective analysis. 2015

Payne, Helen / Mkhize, Nonhlanhla / Otwombe, Kennedy / Lewis, Joanna / Panchia, Ravindre / Callard, Robin / Morris, Lynn / Babiker, Abdel / Violari, Avy / Cotton, Mark F / Klein, Nigel J / Gibb, Diana M. ·Institute of Child Health, University College London, London, UK. Electronic address: helenpayne@doctors.org.uk. · Centre for HIV and Sexually Transmitted Infections, National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa. · Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. · Centre for Maths and Physics in the Life Sciences and Experimental Biology, University College London, London, UK. · Institute of Child Health, University College London, London, UK; Centre for Maths and Physics in the Life Sciences and Experimental Biology, University College London, London, UK. · Clinical Trials Unit, Medical Research Council, London, UK. · Children's Infectious Diseases Clinical Research Unit, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa. · Institute of Child Health, University College London, London, UK. ·Lancet Infect Dis · Pubmed #26043884.

ABSTRACT: BACKGROUND: Early antiretroviral therapy (ART) and virological suppression can affect evolving antibody responses to HIV infection. We aimed to assess frequency and predictors of seronegativity in infants starting early ART. METHODS: We compared HIV antibody results between two of three treatment groups of the Children with HIV Early Antiretroviral Therapy (CHER) trial, done from July, 2005, until July, 2011, in which infants with HIV infection aged 5·7-12·0 weeks with a percentage of CD4-positive T lymphocytes of at least 25% were randomly assigned to immediate ART for 96 weeks (ART-96W) or deferred ART until clinical or immunological progression (ART-Def). We measured antibody from all available stored samples for ART-96W and ART-Def at trial week 84 using three assays: fourth-generation enzyme immunoassay HIV antigen-antibody combination, HIV-1 and HIV-2 rapid antibody test, and quantitative anti-gp120 IgG ELISA. We also assessed odds of seropositivity with respect to age of ART initiation and cumulative viral load. The CHER trial was registered with ClinicalTrials.gov, number NCT00102960. FINDINGS: The median age of the infants from when samples were taken (184 samples from 268 infants) was 92 weeks (IQR 90·6-93·4). More specimens from the ART-96W group were seronegative than from the ART-Def group by enzyme immunoassay (ART-96W 49 [46%] of 107 vs ART-Def eight [11%] of 75; p<0·0001) and rapid antibody test (54 [53%] of 101 vs eight [11%] of 74; p<0·0001). Median anti-gp120 IgG concentration was lower in the ART-96W group (230 μg/μL [IQR 133-13 129]) than in the ART-Def group (6870 μg/μL [1706-53 645]; p<0·0001). If ART was started between 12 and 24 weeks of age, odds of seropositivity were increased 13·7 times (95% CI 3·1-60·2; p=0·001) compared with starting it between 0 and 12 weeks. All children starting ART aged older than 24 weeks were seropositive. Cumulative viral load to week 84 correlated with anti-gp120 IgG concentrations (coefficient 0·54; p<0·0001) and increased odds of seropositivity (odds ratio 1·59 [95% CI 1·1-2·3]) adjusted for ART initiation age. INTERPRETATION: About half of children starting ART before 12 weeks of age were HIV seronegative by almost 2 years of age. HIV antibody tests cannot be used to reconfirm HIV diagnosis in children starting early ART. Long-term effects of seronegativity need further study. Clear guidelines are needed for retesting alongside improved diagnostic tests. FUNDING: Wellcome Trust, Medical Research Council, and National Institutes of Health.

3 Article Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4-8 weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011-12 and 2012-13. 2019

Hunt, Gillian M / Ledwaba, Johanna / Salimo, Anna / Kalimashe, Monalisa / Dinh, Thu-Ha / Jackson, Debra / Sherman, Gayle / Puren, Adrian / Ngandu, Nobubelo K / Lombard, Carl / Morris, Lynn / Goga, Ameena. ·Centre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory Services, Johannesburg, South Africa. gillianh@nicd.ac.za. · Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. gillianh@nicd.ac.za. · Centre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory Services, Johannesburg, South Africa. · US Centers for Disease Control and Prevention, Center for Global Health, Division of Global HIV/TB, Atlanta, GA, USA. · School of Public Health, University of the Western Cape, Bellville, South Africa. · UNICEF, New York, NY, USA. · Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. · Health Systems Research Unit, South African Medical Research Council, Cape Town, South Africa. · Biostatistics Unit, South African Medical Research Council, Cape Town, South Africa. · School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. · Department of Paediatrics, University of Pretoria, Pretoria, South Africa. ·BMC Infect Dis · Pubmed #31526373.

ABSTRACT: BACKGROUND: South Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved antiretroviral regimens and coverage between 2001 and 2016, there is little data on infant HIV drug resistance. This paper tracks the prevalence of HIV drug resistance patterns amongst HIV infected infants from three nationally representative studies that assessed the effectiveness of national programs to prevent MTCT (PMTCT). The first study was conducted in 2010 (under the dual therapy PMTCT policy), the second from 2011 to 12 (PMTCT Option A policy) and the third from 2012 to 13 (PMTCT Option A policy). From 2010 to 2013, infant non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure increased from single dose to daily throughout breastfeeding; maternal nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI exposure increased with initiation of NNRTI-and NRTI- containing triple antiretroviral therapy (ART) earlier in gestation and at higher CD4 cell counts. METHODS: Three nationally representative surveys were conducted in 2010, 2011-12 and 2012-13. During the surveys, mothers with known, unknown, or no exposure to antiretrovirals for PMTCT and their infants were included, and MTCT was measured. For this paper, infant dried blood spots (iDBS) from HIV PCR positive infants aged 4-8 weeks, with consent for additional iDBS testing, were analysed for HIV drug resistance at the National Institute of Communicable Diseases (NICD), SA, using an in-house assay validated by the Centers for Disease Control and Prevention (CDC). Total viral nucleic acid was extracted from 2 spots and amplified by nested PCR to generate a ~ 1 kb amplicon that was sequenced using Sanger sequencing technologies. Sequence assembly and editing was performed using RECall v3. RESULTS: Overall, HIV-1 drug resistance was detected in 51% (95% Confidence interval (CI) [45-58%]) of HIV PCR positive infants, 37% (95% CI [28-47%]) in 2010, 64% (95% CI [53-74%]) in 2011 and 63% (95% CI [47-77%]) in 2012 (p < 0.0001), particularly to the NNRTI drug class. Pooled analyses across all three surveys demonstrated that infants whose mothers received ART showed the highest prevalence of resistance (74%); 26% (21/82) of HIV PCR positive infants with no or undocumented antiretroviral drug (ARV) exposure harboured NNRTI resistance. CONCLUSIONS: These data demonstrate increasing NNRTI resistance amongst newly-diagnosed infants in a high HIV prevalence setting where maternal ART coverage increased across the years, starting earlier in gestation and at higher CD4 cell counts. This is worrying as lifelong maternal ART coverage for HIV positive pregnant and lactating women is increasing. Also of concern is that resistant virus was detected in HIV positive infants whose mothers were not exposed to ARVs, raising questions about circulating resistant virus. Numbers in this group were too small to assess trends over the three years.

4 Article Somatic hypermutation to counter a globally rare viral immunotype drove off-track antibodies in the CAP256-VRC26 HIV-1 V2-directed bNAb lineage. 2019

Sacks, David / Bhiman, Jinal N / Wiehe, Kevin / Gorman, Jason / Kwong, Peter D / Morris, Lynn / Moore, Penny L. ·Centre for HIV and STIs, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Johannesburg, South Africa. · Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. · Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, United States of America. · Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America. · Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa. ·PLoS Pathog · Pubmed #31479499.

ABSTRACT: Previously we have described the V2-directed CAP256-VRC26 lineage that includes broadly neutralizing antibodies (bNAbs) that neutralize globally diverse strains of HIV. We also identified highly mutated "off-track" lineage members that share high sequence identity to broad members but lack breadth. Here, we defined the mutations that limit the breadth of these antibodies and the probability of their emergence. Mutants and chimeras between two pairs of closely related antibodies were generated: CAP256.04 and CAP256.25 (30% and 63% breadth, respectively) and CAP256.20 and CAP256.27 (2% and 59% breadth). Antibodies were tested against 14 heterologous HIV-1 viruses and select mutants to assess breadth and epitope specificity. A single R100rA mutation in the third heavy chain complementarity-determining region (CDRH3) introduced breadth into CAP256.04, but all three CAP256.25 heavy chain CDRs were required for potency. In contrast, in the CAP256.20/27 chimeras, replacing only the CDRH3 of CAP256.20 with that of CAP256.27 completely recapitulated breadth and potency, likely through the introduction of three charge-reducing mutations. In this individual, the mutations that limited the breadth of the off-track antibodies were predicted to occur with a higher probability than those in the naturally paired bNAbs, suggesting a low barrier to the evolution of the off-track phenotype. Mapping studies to determine the viral immunotypes (or epitope variants) that selected off-track antibodies indicated that unlike broader lineage members, CAP256.20 preferentially neutralized viruses containing 169Q. This suggests that this globally rare immunotype, which was common in donor CAP256, drove the off-track phenotype. These data show that affinity maturation to counter globally rare viral immunotypes can drive antibodies within a broad lineage along multiple pathways towards strain-specificity. Defining developmental pathways towards and away from breadth may facilitate the selection of immunogens that elicit bNAbs and minimize off-track antibodies.

5 Article Evidence for both Intermittent and Persistent Compartmentalization of HIV-1 in the Female Genital Tract. 2019

Mabvakure, Batsirai M / Lambson, Bronwen E / Ramdayal, Kavisha / Masson, Lindi / Kitchin, Dale / Allam, Mushal / Abdool Karim, Salim / Williamson, Carolyn / Passmore, Jo-Ann / Martin, Darren P / Scheepers, Cathrine / Moore, Penny L / Harkins, Gordon W / Morris, Lynn. ·Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. · Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. · South African MRC Bioinformatics Capacity Development Unit, South African National Bioinformatics Institute, University of the Western Cape, Cape Town, South Africa. · Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. · Sequencing Core Facility, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. · Centre for the AIDS Programme of Research in South Africa (CAPRISA), KwaZulu-Natal, South Africa. · National Health Laboratory Service, Johannesburg, South Africa. · Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa lynnm@nicd.ac.za. ·J Virol · Pubmed #30842323.

ABSTRACT: HIV-1 has been shown to evolve independently in different anatomical compartments, but studies in the female genital tract have been inconclusive. Here, we examined evidence of compartmentalization using HIV-1 subtype C envelope (Env) glycoprotein genes (gp160) obtained from matched cervicovaginal lavage (CVL) and plasma samples over 2 to 3 years of infection. HIV-1 gp160 amplification from CVL was achieved for only 4 of 18 acutely infected women, and this was associated with the presence of proinflammatory cytokines and/or measurable viremia in the CVL. Maximum likelihood trees and divergence analyses showed that all four individuals had monophyletic compartment-specific clusters of CVL- and/or plasma-derived gp160 sequences at all or some time points. However, two participants (CAP177 and CAP217) had CVL gp160 diversity patterns that differed from those in plasma and showed restricted viral flow from the CVL. Statistical tests of compartmentalization revealed evidence of persistent compartment-specific gp160 evolution in CAP177, while in CAP217 this was intermittent. Lastly, we identified several Env sites that distinguished viruses in these two compartments; for CAP177, amino acid differences arose largely through positive selection, while insertions/deletions were more common in CAP217. In both cases these differences contributed to substantial charge changes spread across the Env. Our data indicate that, in some women, HIV-1 populations within the genital tract can have Env genetic features that differ from those of viruses in plasma, which could impact the sensitivity of viruses in the genital tract to vaginal microbicides and vaccine-elicited antibodies.

6 Article Evolution of an HIV glycan-dependent broadly neutralizing antibody epitope through immune escape. 2012

Moore, Penny L / Gray, Elin S / Wibmer, C Kurt / Bhiman, Jinal N / Nonyane, Molati / Sheward, Daniel J / Hermanus, Tandile / Bajimaya, Shringkhala / Tumba, Nancy L / Abrahams, Melissa-Rose / Lambson, Bronwen E / Ranchobe, Nthabeleng / Ping, Lihua / Ngandu, Nobubelo / Abdool Karim, Quarraisha / Abdool Karim, Salim S / Swanstrom, Ronald I / Seaman, Michael S / Williamson, Carolyn / Morris, Lynn. ·Centre for HIV and STI, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. ·Nat Med · Pubmed #23086475.

ABSTRACT: Neutralizing antibodies are likely to play a crucial part in a preventative HIV-1 vaccine. Although efforts to elicit broadly cross-neutralizing (BCN) antibodies by vaccination have been unsuccessful, a minority of individuals naturally develop these antibodies after many years of infection. How such antibodies arise, and the role of viral evolution in shaping these responses, is unknown. Here we show, in two HIV-1-infected individuals who developed BCN antibodies targeting the glycan at Asn332 on the gp120 envelope, that this glycan was absent on the initial infecting virus. However, this BCN epitope evolved within 6 months, through immune escape from earlier strain-specific antibodies that resulted in a shift of a glycan to position 332. Both viruses that lacked the glycan at amino acid 332 were resistant to the Asn332-dependent BCN monoclonal antibody PGT128 (ref. 8), whereas escaped variants that acquired this glycan were sensitive. Analysis of large sequence and neutralization data sets showed the 332 glycan to be significantly under-represented in transmitted subtype C viruses compared to chronic viruses, with the absence of this glycan corresponding with resistance to PGT128. These findings highlight the dynamic interplay between early antibodies and viral escape in driving the evolution of conserved BCN antibody epitopes.