scholarly journals Rapid accumulation of HIV-1 thymidine analogue mutations and phenotypic impact following prolonged viral failure on zidovudine-based first-line ART in sub-Saharan Africa

2017 ◽  
Vol 72 (5) ◽  
pp. 1450-1455 ◽  
Author(s):  
Ruth L. Goodall ◽  
David T. Dunn ◽  
Peter Nkurunziza ◽  
Lincoln Mugarura ◽  
Theresa Pattery ◽  
...  
Keyword(s):  
Sub Saharan Africa ◽  
First Line ◽  
Thymidine Analogue ◽  
Rapid Accumulation ◽  
Sub Saharan ◽  
Hiv 1

An apparent paradox: resistance mutations in HIV-1 DNA predict improved virological responses to antiretroviral therapy

2019 ◽  
Vol 74 (10) ◽  
pp. 3011-3015 ◽  
Author(s):  
Anna Maria Geretti ◽  
Adam Abdullahi ◽  
Olga Mafotsing Fopoussi ◽  
Laura Bonnett ◽  
Victoire Fokom Defo ◽  
...  
Keyword(s):  
Viral Load ◽  
Virological Failure ◽  
Dna Sequences ◽  
Sub Saharan Africa ◽  
Resistance Mutations ◽  
First Line ◽  
Second Line Therapy ◽  
Apparent Paradox ◽  
Sub Saharan ◽  
Hiv 1

Abstract Background In sub-Saharan Africa, detecting resistance-associated mutations (RAMs) at failure of first-line ART with two NRTIs plus an NNRTI predicts improved virological responses to second-line therapy with two NRTIs plus a ritonavir-boosted PI (PI/r). This indicates residual NRTI activity in the presence of RAMs, although additional factors may contribute to the effect. Objectives The aim of this study was to investigate the influence of pre-existing RAMs on the outcomes of maintenance monotherapy with ritonavir-boosted darunavir within a randomized trial in Cameroon. Methods RAMs were detected in HIV-1 DNA using PBMCs collected at initiation of darunavir/ritonavir monotherapy. Adherence was assessed by pill count and visual analogue scale (VAS). Predictors of virological failure (confirmed or last available viral load >400 copies/mL) were explored by logistic regression analysis. Trial name = MANET (NCT02155101). Results After NNRTI-based therapy, participants (n = 81) had received PI/r-based therapy for a median of 3.2 years and had a confirmed viral load <60 copies/mL and a median CD4 count of 466 cells/mm3. NRTI and NNRTI RAMs were detected in 39/60 (65.0%) and 41/60 (68.3%) HIV-1 DNA sequences, respectively. Over 48 weeks of monotherapy, 16/81 (19.8%) patients experienced virological failure. After adjusting for age, HIV-1 DNA load, adherence by VAS and RAM status, virological failure was less likely with higher VAS-measured adherence (adjusted OR 0.04, 95% CI 0.01–0.37; P = 0.004) and detectable HIV-1 DNA RAMs (adjusted OR 0.15, 95% CI 0.03–0.82; P = 0.028). Conclusions Pre-existing NRTI and NNRTI RAMs are associated with improved virological responses to NRTI-sparing ART in sub-Saharan Africa, indicating a predictive effect that is independent of residual NRTI activity.

scholarly journals Accumulation of HIV-1 drug resistance after continued virological failure on first-line ART in adults and children in sub-Saharan Africa

2016 ◽  
Vol 71 (10) ◽  
pp. 2918-2927 ◽  
Author(s):  
T. Sonia Boender ◽  
Cissy M. Kityo ◽  
Ragna S. Boerma ◽  
Raph L. Hamers ◽  
Pascale Ondoa ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Virological Failure ◽  
Sub Saharan Africa ◽  
First Line ◽  
Adults And Children ◽  
Sub Saharan ◽  
Hiv 1

scholarly journals Active Components from Cassia abbreviata Prevent HIV-1 Entry by Distinct Mechanisms of Action

2021 ◽  
Vol 22 (9) ◽  
pp. 5052
Author(s):  
Yue Zheng ◽  
Xian-Wen Yang ◽  
Dominique Schols ◽  
Mattia Mori ◽  
Bruno Botta ◽  
...  
Keyword(s):  
Crude Extract ◽  
Female Genital Tract ◽  
Binding Activity ◽  
Sub Saharan Africa ◽  
Active Components ◽  
Chemical Structures ◽  
3D Space ◽  
In Silico Study ◽  
Sub Saharan ◽  
Hiv 1

Cassia abbreviata is widely used in Sub-Saharan Africa for treating many diseases, including HIV-1 infection. We have recently described the chemical structures of 28 compounds isolated from an alcoholic crude extract of barks and roots ofC. abbreviata, and showed that six bioactive compounds inhibit HIV-1 infection. In the present study, we demonstrate that the six compounds block HIV-1 entry into cells: oleanolic acid, palmitic acid, taxifolin, piceatannol, guibourtinidol-(4α®8)-epiafzelechin, and a novel compound named as cassiabrevone. We report, for the first time, that guibourtinidol-(4α®8)-epiafzelechin and cassiabrevone inhibit HIV-1 entry (IC50 of 42.47 µM and 30.96 µM, respectively), as well as that piceatannol interacts with cellular membranes. Piceatannol inhibits HIV-1 infection in a dual-chamber assay mimicking the female genital tract, as well as HSV infection, emphasizing its potential as a microbicide. Structure-activity relationships (SAR) showed that pharmacophoric groups of piceatannol are strictly required to inhibit HIV-1 entry. By a ligand-based in silico study, we speculated that piceatannol and norartocarpetin may have a very similar mechanism of action and efficacy because of the highly comparable pharmacophoric and 3D space, while guibourtinidol-(4α®8)-epiafzelechin and cassiabrevone may display a different mechanism. We finally show that cassiabrevone plays a major role of the crude extract of CA by blocking the binding activity of HIV-1 gp120 and CD4.

scholarly journals A Randomized Switch From Nevirapine-Based Antiretroviral Therapy to Single Tablet Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in Virologically Suppressed Human Immunodeficiency Virus-1-Infected Rwandans

2016 ◽  
Vol 3 (3) ◽  
Author(s):  
Sean E. Collins ◽  
Philip M. Grant ◽  
Francois Uwinkindi ◽  
Annie Talbot ◽  
Eric Seruyange ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Tenofovir Disoproxil Fumarate ◽  
Sub Saharan Africa ◽  
Current Therapy ◽  
Virologic Suppression ◽  
Open Label ◽  
Immunodeficiency Virus ◽  
Sub Saharan ◽  
Hiv 1

Abstract Background.  Many human immunodeficiency virus (HIV)-infected patients remain on nevirapine-based antiretroviral therapy (ART) despite safety and efficacy concerns. Switching to a rilpivirine-based regimen is an alternative, but there is little experience with rilpivirine in sub-Saharan Africa where induction of rilpivirine metabolism by nevirapine, HIV subtype, and dietary differences could potentially impact efficacy. Methods.  We conducted an open-label noninferiority study of virologically suppressed (HIV-1 ribonucleic acid [RNA] &lt; 50 copies/mL) HIV-1-infected Rwandan adults taking nevirapine plus 2 nucleos(t)ide reverse-transcriptase inhibitors. One hundred fifty participants were randomized 2:1 to switch to coformulated rilpivirine-emtricitabine-tenofovir disoproxil fumarate (referenced as the Switch Arm) or continue current therapy. The primary efficacy endpoint was HIV-1 RNA &lt; 200 copies/mL at week 24 assessed by the US Food and Drug Administration Snapshot algorithm with a noninferiority margin of 12%. Results.  Between April and September 2014, 184 patients were screened, and 150 patients were enrolled; 99 patients switched to rilpivirine-emtricitabine-tenofovir, and 51 patients continued their nevirapine-based ART. The mean age was 42 years and 43% of participants were women. At week 24, virologic suppression (HIV-1 RNA level &lt;200 copies/mL) was maintained in 93% and 92% in the Switch Arm versus the continuation arm, respectively. The Switch Arm was noninferior to continued nevirapine-based ART (efficacy difference 0.8%; 95% confidence interval, −7.5% to +12.0%). Both regimens were generally safe and well tolerated, although 2 deaths, neither attributed to study medications, occurred in participants in the Switch Arm. Conclusions.  A switch from nevirapine-based ART to rilpivirine-emtricitabine-tenofovir disoproxil fumarate had similar virologic efficacy to continued nevirapine-based ART after 24 weeks with few adverse events.

scholarly journals HIV-1 Full-Genome Phylogenetics of Generalized Epidemics in Sub-Saharan Africa: Impact of Missing Nucleotide Characters in Next-Generation Sequences

2017 ◽  
Vol 33 (11) ◽  
pp. 1083-1098 ◽  
Author(s):  
Oliver Ratmann ◽  
Chris Wymant ◽  
Caroline Colijn ◽  
Siva Danaviah ◽  
Max Essex ◽  
...  
Keyword(s):  
Sub Saharan Africa ◽  
Full Genome ◽  
Next Generation ◽  
Sub Saharan ◽  
Hiv 1
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