High Prevalence of Cross-resistance to Rilpivirine in Subtype C HIV-1 Isolates from First-line ART Failures in South Africa

2014 ◽  
Vol 30 (S1) ◽  
pp. A166-A166 ◽  
Author(s):  
Kerri J. Penrose ◽  
Carole L. Wallis ◽  
Maritsa Scoulos-Hanson ◽  
Raquel Viana ◽  
John W. Mellors ◽  
...  
Keyword(s):  
South Africa ◽  
Cross Resistance ◽  
Subtype C ◽  
First Line ◽  
High Prevalence ◽  
Hiv 1

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 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa

2018 ◽  
Vol 26 ◽  
pp. 204020661876298 ◽  
Author(s):  
Kerri J Penrose ◽  
Chanson J Brumme ◽  
Maritsa Scoulos-Hanson ◽  
Kristen Hamanishi ◽  
Kelley Gordon ◽  
...  
Keyword(s):  
South Africa ◽  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Transcriptase Inhibitor ◽  
Cross Resistance ◽  
Subtype C ◽  
First Line ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

Background Rilpivirine (TMC278LA) is a promising drug for pre-exposure prophylaxis of HIV-1 because of its sub-nanomolar potency and long-acting formulation; however, increasing transmission of non-nucleoside reverse transcriptase inhibitor-resistant HIV-1 with potential cross-resistance to rilpivirine could reduce its preventive efficacy. This study investigated rilpivirine cross-resistance among recombinant subtype C HIV-1 derived from 100 individuals failing on first-line non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy in South Africa whose samples were sent for routine HIV-1 drug resistance testing to Lancet Laboratories (Johannesburg, South Africa). Methods Plasma samples were selected from individuals with HIV-1 RNA > 10,000 copies/ml and ≥1 non-nucleoside reverse transcriptase inhibitor-resistance mutation in reverse transcriptase. Recombinant HIV-1LAI-containing bulk-cloned full-length reverse transcriptase sequences from plasma were assayed for susceptibility to nevirapine (NVP), efavirenz (EFV) and rilpivirine in TZM-bl cells. Fold-change (FC) decreases in drug susceptibility were calculated against a mean IC50 from 12 subtype C HIV-1 samples from treatment-naïve individuals in South Africa. Cross-resistance was evaluated based on biological cutoffs established for rilpivirine (2.5-FC) and the effect of mutation combinations on rilpivirine phenotype. Results Of the 100 samples from individuals on failing antiretroviral therapy, 69 had 2.5- to 75-fold decreased susceptibility to rilpivirine and 11 had >75-fold resistance. Rilpivirine resistance was strongly associated with K103N especially in combination with other rilpivirine-associated mutations. Conclusion The frequently observed cross-resistance of HIV-1 suggests that the preventive efficacy of TMC278LA pre-exposure prophylaxis could be compromised by transmission of HIV-1 from individuals with failure of first-line non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy.

scholarly journals Frequent Cross-Resistance to Dapivirine in HIV-1 Subtype C-Infected Individuals after First-Line Antiretroviral Therapy Failure in South Africa

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Kerri J. Penrose ◽  
Carole L. Wallis ◽  
Chanson J. Brumme ◽  
Kristen A. Hamanishi ◽  
Kelley C. Gordon ◽  
...  
Keyword(s):  
South Africa ◽  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Plasma Concentrations ◽  
Cross Resistance ◽  
Subtype C ◽  
First Line ◽  
Nnrti Mutation ◽  
Treatment Naïve ◽  
Hiv 1

ABSTRACT A vaginal ring containing dapivirine (DPV) has shown moderate protective efficacy against HIV-1 acquisition, but the activity of DPV against efavirenz (EFV)- and nevirapine (NVP)-resistant viruses that could be transmitted is not well defined. We investigated DPV cross-resistance of subtype C HIV-1 from individuals on failing NVP- or EFV-containing antiretroviral therapy (ART) in South Africa. Plasma samples were obtained from individuals with >10,000 copies of HIV RNA/ml and with HIV-1 containing at least one non-nucleoside reverse transcriptase (NNRTI) mutation. Susceptibility to NVP, EFV, and DPV in TZM-bl cells was determined for recombinant HIV-1LAI containing bulk-amplified, plasma-derived, full-length reverse transcriptase sequences. Fold change (FC) values were calculated compared with a composite 50% inhibitory concentration (IC50) from 12 recombinant subtype C HIV-1LAI plasma-derived viruses from treatment-naive individuals in South Africa. A total of 25/100 (25%) samples showed >500-FCs to DPV compared to treatment-naive samples with IC50s exceeding the maximum DPV concentration tested (132 ng/ml). A total of 66/100 (66%) samples displayed 3- to 306-FCs, with a median IC50 of 17.6 ng/ml. Only 9/100 (9%) samples were susceptible to DPV (FC < 3). Mutations L100I and K103N were significantly more frequent in samples with >500-fold resistance to DPV compared to samples with a ≤500-fold resistance. A total of 91% of samples with NNRTI-resistant HIV-1 from individuals on failing first-line ART in South Africa exhibited ≥3-fold cross-resistance to DPV. This level of resistance exceeds expected plasma concentrations, but very high genital tract DPV concentrations from DPV ring use could block viral replication. It is critically important to assess the frequency of transmitted and selected DPV resistance in individuals using the DPV ring.

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 Viremia, Resuppression, and Time to Resistance in Human Immunodeficiency Virus (HIV) Subtype C during First‐Line Antiretroviral Therapy in South Africa

2009 ◽  
Vol 49 (12) ◽  
pp. 1928-1935 ◽  
Author(s):  
Christopher J. Hoffmann ◽  
Salome Charalambous ◽  
John Sim ◽  
Joanna Ledwaba ◽  
Graham Schwikkard ◽  
...  
Keyword(s):  
South Africa ◽  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Subtype C ◽  
First Line ◽  
Immunodeficiency Virus

scholarly journals Antibiotic resistance profiles of Campylobacter species in the South Africa private health care sector

2016 ◽  
Vol 10 (11) ◽  
pp. 1214-1221 ◽  
Author(s):  
Christiana O. Shobo ◽  
Linda Antionette Bester ◽  
Sooraj Baijnath ◽  
Anou M. Somboro ◽  
Abdool K.C. Peer ◽  
...  
Keyword(s):  
South Africa ◽  
South African ◽  
Dilution Method ◽  
Surveillance Program ◽  
Private Health Care ◽  
First Line ◽  
Pathology Laboratory ◽  
Healthcare Environment ◽  
High Prevalence ◽  
Human Campylobacteriosis

Introduction: There is a dearth of surveillance data on clinical Campylobacter in South Africa, particularly in the private healthcare environment. We investigated the prevalence of resistance to first-line antibiotics used to treat campylobacterioses in clinical Campylobacter isolates from a private pathology laboratory. Methodology: Identification of the Campylobacter specific genes were confirmed by PCR. Minimum inhibitory concentrations were determined using the broth micro-dilution method against macrolides (erythromycin, azithromycin), fluoroquinolones (ciprofloxacin, gatifloxacin) and tetracycline. Results: Seventy-two Campylobacter isolates were identified by PCR, with 54 (75%) being classified as C. jejuni and 18 (25%) as C. coli. Of these, 11 (20.4%) C. jejuni and six (33.3%) C. coli strains were resistant to ciprofloxacin and three (7.41%) C. jejuni and three (16.7%) C. coli strains were resistant to gatifloxacin. The number of C. jejuni strains resistant to erythromycin and azithromycin was 17 (31.5%) and 36 (50%) respectively, while the resistance of C. coli strains to erythromycin and azithromycin were seven (38.9%) and 14 (77.8%) respectively. Resistance to tetracycline was detected in 10 (55.6%) C. coli and 14 (25.9%) C. jejuni strains. Conclusion: In the light of these resistant profiles, the lack of a South African Campylobacter surveillance program is of concern. Relatively high prevalence of resistance in clinical isolates of C. jejuni and C. coli to the fluoroquinolones, macrolides and tetracycline used in first line treatment is of great concern. The efficacy treating human campylobacteriosis should thus be revisited.

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