Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi

Neuhann, Florian; Forest, Andrew de; Heger, Eva; Nhlema, Angellina; Scheller, Carsten; Kaiser, Rolf; Steffen, Hans‐Michael; Tweya, Hannock; Fätkenheuer, Gerd; Phiri, Sam

doi:10.1186/s12981-020-00282-3

Cited by 10 publications

(9 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study specifically shows that the most common mutation for the NNRTI (K103N) selected by EFV and NVP is also observed in other countries from the southern region of Africa [35,36,48,52,58]. This mutation is selected by EFV and NVP, and usually viruses with the K103N mutation have transmission fitness like wild-type viruses [59] which can persist for many years in the infected host.…”

Section: Discussionmentioning

confidence: 56%

“…To obtain a broader picture of the HIV-1 genetic epidemiology, we analyzed 865 pol sequences reported from 8 different study datasets. Not surprisingly, subtype C predominated throughout time in Mozambique, which accounts for most infections in southern Africa [35][36][37], showing the limited need to monitor subtype distribution over time in the country. However, a higher frequency for non-C HIV-1 was observed in the north of the as previously described in other studies [12,21].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Epidemiology and Trends in HIV-1 Transmitted Drug Resistance in Mozambique 1999–2018

Ismael

Wilkinson

Mahumane

et al. 2022

Viruses

View full text Add to dashboard Cite

HIV drug resistance (HIVDR) can become a public health concern, especially in low- and middle-income countries where genotypic testing for people initiating antiretroviral therapy (ART) is not available. For first-line regimens to remain effective, levels of transmitted drug resistance (TDR) need to be monitored over time. To determine the temporal trends of TDR in Mozambique, a search for studies in PubMed and sequences in GenBank was performed. Only studies covering the pol region that described HIVDR and genetic diversity from treatment naïve patients were included. A dataset from seven published studies and one novel unpublished study conducted between 1999 and 2018 were included. The Calibrated Population Resistance tool (CPR) and REGA HIV-1 Subtyping Tool version 3 for sequences pooled by sampling year were used to determine resistance mutations and subtypes, respectively. The prevalence of HIVDR amongst treatment-naïve individuals increased over time, reaching 14.4% in 2018. The increase was most prominent for non-nucleoside reverse transcriptase inhibitors (NNRTIs), reaching 12.7% in 2018. Subtype C was predominant in all regions, but a higher genetic variability (19% non-subtype C) was observed in the north region of Mozambique. These findings confirm a higher diversity of HIV in the north of the country and an increased prevalence of NNRTI resistance among treatment naïve individuals over time.

show abstract

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Molecular Epidemiology and Trends in HIV-1 Transmitted Drug Resistance in Mozambique 1999–2018

Ismael

Wilkinson

Mahumane

et al. 2022

Viruses

View full text Add to dashboard Cite

show abstract

“…Some studies believe that PDR is not correlated with VF or survival rate, [5,19] but others believe that PDR is related to VF. [20–22] In our study, there were more cases of treatment failure in the PDR arm, where PDR affected the CD4 + T-cell counts at 12 weeks after ART. This suggests the profound impact of PDR on ART in patients with HIV.…”

Section: Discussionmentioning

confidence: 66%

Pre-treatment Drug Resistance Could Impact the 96-Week Antiretroviral Efficacy in Treatment-Naive HIV-1–Infected Patients in Guangdong, China

Guo¹,

Lan²,

Li³

et al. 2022

Infect Dis Immun

View full text Add to dashboard Cite

BackgroundWith the high prevalence of pre-treatment drug resistance (PDR) and the potential impact to the virological inhibition, the detection of PDR was particularly necessary. This study aimed to determine the prevalence of PDR in Guangdong, China, and its impact on antiretroviral therapy (ART) in treatment-naive HIV patients.MethodsA retrospective cohort study was conducted. A total of 1936 HIV-1–infected treatment-naive patients in the clinic of the infectious department, Guangzhou Eighth People’s Hospital, between August 2018 and December 2019 were assayed for PDR mutations before initiating ART. Patients with PDR mutations (PDR arm) were screened and compared with those without drug-resistant mutations (non-PDR arm). The rate of HIV-1 virologic failure (VF) and CD4+ T-cell counts of the 2 arms were compared at the 96th week after ART to evaluate the impact of PDR on the efficacy of ART.ResultsPretreatment drug resistance was detected in 125 cases (6.46%) from the 1936 enrolled participants, most of which were resistant to non-nucleoside reverse transcriptase inhibitors (64.00%, 80/125). One hundred and eight of 125 completed the follow-up of 96 weeks (PDR arm). In this cohort, 52 patients whose ART regimen containing the resistant drug were grouped as con-PDR arm, and the remaining 56 patients whose ART regimen did not contain the resistant drug were grouped as non- con-PDR arm. A total of 125 patients without PDR were randomly selected as the control group (non-PDR arm), 112 of whom had completed the 96-week follow-up. At the 96th week after ART initiation, 7 patients (6.5%, 7/108) in the PDR arm and 1 patient (0.9%, 1/112) in the non-PDR arm developed VF, exhibiting a significant difference (χ2 = 4.901, P = 0.029). Meanwhile, 3 patients (5.8%, 3/52) in the con-PDR arm developed VF; the rate was also higher than that in the non-PDR arm, but without a significant difference (χ2 = 3.549, P = 0.095). The CD4+ T-cell count in the non-PDR arm increased more than the PDR arm (386.6 vs. 319.1 cells/μL, t = 2.448, P = 0.015) or the con-PDR arm (386.6 vs. 325.1 cells/μL, t = 1.821, P = 0.070) at 12 weeks after ART. However, no significant differences were observed in the CD4+ T-cell count from the 24th week after ART onward.ConclusionsPretreatment drug resistance was moderately prevalent in Guangdong, China, and could affect the antiretroviral efficacy during a 96-week observation period, indicating the need to closely monitor PDR before ART initiation.

show abstract

“…Many of the PLWH on second-line ART will probably have a history of poor adherence, which led to virologic failure on first-line ART and, in some patients, could have led to the development of drug resistance. However, NNRTI pretreatment resistance likely played a more significant role in the last decade [24][25][26][27]. Second-line virologic failure (DTG or ATV/r) may more likely be related to poor treatment compliance based on literature showing almost no pretreatment or transmitted drug resistance among protease inhibitor-and INSTI-naïve PLWH in Zimbabwe and the demonstrated efficacy of both DTG and protease inhibitors with suboptimal NRTI backbones [15,25,[28][29][30].…”

Section: Discussionmentioning

confidence: 99%

Virologic outcomes on dolutegravir-, atazanavir-, or efavirenz-based ART in urban Zimbabwe: A longitudinal study

Shamu,

Egger,

Mudzviti

et al. 2023

Preprint

View full text Add to dashboard Cite

There are few data from sub-Saharan Africa on the virologic outcomes associated with second-line ART based on protease inhibitors or dolutegravir (DTG). We compared viral load (VL) suppression among people living with HIV (PLWH) on atazanavir (ATV/r)- or dolutegravir (DTG)-based second-line ART with PLWH on efavirenz (EFV)-based first-line ART. We analyzed data from the electronic medical records system of Newlands Clinic in Harare, Zimbabwe. We included patients aged >=12 years when commencing first-line EFV-based ART or switching to second-line DTG- or ATV/r-based ART with >=24 weeks follow-up after start or switch. We computed suppression rates (HIV VL <50 copies/mL) at weeks 12, 24, 48, 72, and 96 and estimated the probability of VL suppression by treatment regimen, time since start/switch of ART, sex, age, and CD4 cell count (at start/switch) using logistic regression in a Bayesian framework. We included 7013 VL measurements of 1049 PLWH (61% female) initiating first-line ART and 1114 patients (58% female) switching to second-line ART. Among those switching, 872 (78.3%) were switched to ATV/r and 242 (21.7%) to DTG. VL suppression was lower in second-line ART patients than first-line ART patients, except at week 12, when those on DTG showed higher suppression than those on EFV (aOR 2.10, 95%-credible interval [CrI] 1.48-3.00) and ATV/r-based regimens (aOR 1.87, 95%-CrI 1.32-2.71). In weeks >=48, first-line patients had around 3 times the odds of VL suppression compared to second-line patients. There was no evidence of a difference between DTG and ATV/r for follow-up times >24 weeks in PLWH on second-line. Second-line ART patients had lower VL suppression rates than those receiving first-line ART, and there was no difference in suppression between DTG- and ATV/r-based second-line ART >6 months after switching. Virologic monitoring and adherence support remain essential to prevent second-line treatment failure in settings with limited treatment options.

show abstract

Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi

Cited by 10 publications

References 12 publications

Molecular Epidemiology and Trends in HIV-1 Transmitted Drug Resistance in Mozambique 1999–2018

Molecular Epidemiology and Trends in HIV-1 Transmitted Drug Resistance in Mozambique 1999–2018

Pre-treatment Drug Resistance Could Impact the 96-Week Antiretroviral Efficacy in Treatment-Naive HIV-1–Infected Patients in Guangdong, China

Virologic outcomes on dolutegravir-, atazanavir-, or efavirenz-based ART in urban Zimbabwe: A longitudinal study

Contact Info

Product

Resources

About