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 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat

2021 ◽  
Vol 14 ◽  
pp. 117863372110145
Author(s):  
Aristid Ekollo Mbange ◽  
Abou Abdallah Malick Diouara ◽  
Halimatou Diop-Ndiaye ◽  
Ndèye Aminata Diaw Diouf ◽  
Ndèye Fatou Ngom-Ngueye ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Virological Failure ◽  
Sub Saharan Africa ◽  
Treatment Center ◽  
First Line ◽  
Hiv Diagnosis ◽  
Saint Louis ◽  
Test And Treat ◽  
Adherence Support ◽  
Hiv 1

Background: The feasibility of antiretroviral therapy (ART) monitoring remains problematic in decentralized HIV clinic settings of sub-Saharan Africa. We assessed the rates and correlates of HIV-1 virological failure (VF) and drug resistance (DR) in 2 pre-test-and-treat urban clinic settings of Senegal. Methods: Consenting HIV-1-infected adults (⩾18 years) receiving first-line ART for ⩾12 months were cross-sectionally enrolled between January and March 2015, at the referral outpatient treatment center of Dakar (n = 151) and decentralized regional hospital of Saint-Louis (n = 127). In the 12 months preceding plasma specimens’ collection patients at Saint-Louis had no viral load (VL) testing. Significant predictors of VF (VL ⩾ 1000 copies/ml) and DR (clinically relevant mutations) were determined using binomial logistic regression in R software. Results: Of the 278 adults on EFV-/NVP-based regimens, 32 (11.5% [95%CI: 8.0-15.9]) experienced VF. Failing and non-failing patients had comparable median time [interquartile] on ART (69.5 [23.0-89.5] vs 64.0 [34.0-99.0] months; P = .46, Mann–Whitney U-test). Of the 27 viraemic isolates successfully genotyped, 20 (74.1%) carried DR mutations; most frequent were M184VI (55.6%), K103N (37.1%), thymidine analog mutations (29.6%), Y181CY (22.2%). The pattern of mutations did not always correspond to the ongoing treatment. The adjusted odds of VF was significantly associated with the decentralized clinic site ( P < .001) and CD4 < 350 cells/mm3 ( P < .006). Strong correlates of DR also included Saint-Louis ( P < .009), CD4 < 350 cells/mm3 ( P <. 001), and nevirapine-based therapies (comparator: efavirenz-based therapies; P < .027). In stratification analyses by site, higher rate of VF at Saint-Louis (20.5% [95%CI: 13.8-28.5] vs 4.0% [95%CI: 1.5-8.5] in Dakar) was associated with nevirapine-based therapies (OR = 3.34 [1.07-11.75], P = .038), self-reported missing doses (OR = 3.30 [1.13-10.24], P = .029), and medical appointments (OR = 2.91 [1.05-8.47], P = .039) in the last 1 and 12 months(s), respectively. The higher rate of DR at Saint-Louis (12.9% [95%CI: 7.6-20.1] vs 2.7% [95%CI: 0.7-6.7] in Dakar) was associated with nevirapine-based therapies (OR = 5.13 [1.12-37.35], P = .035). Conclusion: At decentralized urban settings, there is need for enhanced virological monitoring and adherence support. HIV programs in Senegal should intensify early HIV diagnosis for effective test-and-treat. These interventions, in addition to the superiority of efavirenz-based therapies provide a favorable framework for transitioning to the recommended potent drug dolutegravir, thereby ensuring its long-term use.

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 Evolution of HIV-1 drug resistance after virological failure of first-line antiretroviral therapy in Lusaka Zambia

2019 ◽  
Vol 24 (4) ◽  
pp. 291-300
Author(s):  
F Parker Hudson ◽  
Lloyd Mulenga ◽  
Andrew O Westfall ◽  
Ranjit Warrier ◽  
Aggrey Mweemba ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Virological Failure ◽  
First Line ◽  
Hiv 1

scholarly journals 885. HIV-1 Treatment Failure and Extensive Drug Resistance in Perinatally Infected Children Failing First-Line Antiretroviral Therapy in Western Kenya

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S20-S20
Author(s):  
Winstone Nyandiko ◽  
Sabina Holland ◽  
Rachel Vreeman ◽  
Allison DeLong ◽  
Akarsh Manne ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Failure ◽  
Cd4 Count ◽  
Sub Saharan Africa ◽  
Resistance Testing ◽  
Second Line ◽  
First Line ◽  
Western Kenya ◽  
Extensive Drug Resistance ◽  
Sub Saharan

Abstract Background Understanding drug resistance in perinatally HIV-infected children (PHIC) when viral load (VL) monitoring is limited is critical for life-long antiretroviral use. Resistance data in PHIC in sub-Saharan Africa are limited. Though guidelines recommend PI-based first-line regimens in PHIC, many worldwide remain on NNRTI-based regimens. We examined treatment failure, resistance, and outcomes in Kenyan PHIC on first-line NNRTI-based therapy. Methods PHIC were enrolled in 2010–2013 at the Academic Model Providing Access to Healthcare in Eldoret, Kenya, a large program caring for >160,000 HIV patients; >15,000 PHIC. VL testing, not routinely available then, was done for all, and resistance testing was done in viremic PHIC. Clinical data were derived from medical records. Subtype and resistance interpretation were with Stanford Database tools. Associations between failure (>1,000 copies/mL) or resistance, and demographic, clinical or lab variables were evaluated with Fisher exact and Wilcoxon rank-sum tests. Results Of 482 PHIC enrolled, 52% were female, median age 8.4 years (range 1–15), median CD4% 28 (range 0–53), 79% on zidovudine (AZT)/abacavir (ABC)+lamivudine(3TC)+efavirenz (EFV)/nevirapine (NVP) for median 2.3 years. Treatment failure was seen in 31%, associated with low CD4% and count. Genotypes were available in 124, 47% female, median age 8.3 years (range 2–15), median CD4% 22 (range 0–45), 81% on AZT/ABC+3TC+EFV/NVP for median 2.5 years, median VL 7,515 copies/mL. Subtypes were A 76%, C 3%, D 15%, recombinants 6%. Reverse transcriptase mutations were in 93%; 93%-NNRTIs, median 2/patient, most common Y181C (44%); 89%-NRTIs, median 3/patient, most common M184V (85%); 89%-dual class, median 5/patient. Intermediate-high resistance to potential second-line drugs included 62% etravirine, 66% rilpivirine, and 19% tenofovir. Of 92/124 (74%) PHIC with follow-up data, 27% remained on NNRTI-based first-line (median CD4 count 461), of whom 24% had suppressed VL and 48% died; and 73% switched to PI-based second-line (median CD4 count 591), of whom 72% had suppressed VL and 6% died (P < 0.05 for both). Conclusion PHIC in western Kenya on NNRTI-based first-line regimens had high treatment failure rates and extensive drug resistance with poor clinical outcomes, demanding urgent interventions. Disclosures All Authors: No reported Disclosures.

Preexposure prophylaxis will have a limited impact on HIV-1 drug resistance in sub-Saharan Africa

AIDS ◽  
2013 ◽  
Vol 27 (18) ◽  
pp. 2943-2951 ◽  
Author(s):  
David A.M.C. van de Vijver ◽  
Brooke E. Nichols ◽  
Ume L. Abbas ◽  
Charles A.B. Boucher ◽  
Valentina Cambiano ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Sub Saharan Africa ◽  
Limited Impact ◽  
Preexposure Prophylaxis ◽  
Sub Saharan ◽  
Hiv 1
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