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 Safety, Tolerability, and Efficacy of Generic Dolutegravir-containing Antiretroviral Therapy Regimens Among South Indian Human Immunodeficiency Virus-infected Patients

2018 ◽  
Vol 68 (6) ◽  
pp. 1048-1051 ◽  
Author(s):  
Nagalingeswaran Kumarasamy ◽  
Sandeep Prabhu ◽  
Ezhilarasi Chandrasekaran ◽  
Selvamuthu Poongulali ◽  
Amrose Pradeep ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Prospective Cohort ◽  
Large Scale ◽  
First Line ◽  
South Indian ◽  
Resource Setting ◽  
Low Resource Setting ◽  
Immunodeficiency Virus

AbstractIn this first study of generic dolutegravir (DTG)-containing regimens in a low-resource setting, we assessed safety, tolerability, and efficacy within a prospective cohort of 564 patients with at least 6 months of clinical follow-up. We provide support for a large-scale transition to DTG as part of first-line regimens.

scholarly journals Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I

2019 ◽  
Vol 222 (7) ◽  
pp. 1108-1116 ◽  
Author(s):  
J Gregson ◽  
S Y Rhee ◽  
R Datir ◽  
D Pillay ◽  
C F Perno ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Replication Capacity ◽  
Compensatory Mutation ◽  
First Line ◽  
Virus Load ◽  
Immunodeficiency Virus ◽  
Human Immunodeficiency Virus 1

Abstract Background M184V/I cause high-level lamivudine (3TC) and emtricitabine (FTC) resistance and increased tenofovir disoproxil fumarate (TDF) susceptibility. Nonetheless, 3TC and FTC (collectively referred to as XTC) appear to retain modest activity against human immunodeficiency virus-1 with these mutations possibly as a result of reduced replication capacity. In this study, we determined how M184V/I impacts virus load (VL) in patients failing therapy on a TDF/XTC plus nonnucleoside reverse-transcriptase inhibitor (NNRTI)-containing regimen. Methods We compared VL in the absence and presence of M184V/I across studies using random effects meta-analysis. The effect of mutations on virus reverse-transcriptase activity and infectiousness was analyzed in vitro. Results M184I/V was present in 817 (56.5%) of 1445 individuals with virologic failure (VF). Virus load was similar in individuals with or without M184I/V (difference in log10 VL, 0.18; 95% confidence interval, .05–.31). CD4 count was lower both at initiation of antiretroviral therapy and at VF in participants who went on to develop M184V/I. L74I was present in 10.2% of persons with M184V/I but absent in persons without M184V/I (P < .0001). In vitro, L74I compensated for defective replication of M184V-mutated virus. Conclusions Virus loads were similar in persons with and without M184V/I during VF on a TDF/XTC/NNRTI-containing regimen. Therefore, we did not find evidence for a benefit of XTC in the context of first-line failure on this combination.

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.

Sign in / Sign up

Export Citation Format

Share Document