Prevalence Trend of Transmitted Drug Resistance in a Prospective Cohort of Thai People with Acute HIV Infection

Abstract Background: In the absence of AIDS vaccine，antiretroviral therapy (ART) was the most effective tool to prevent and control the HIV pandemic. But the widespread use of ART has raised concerns about the emergence of HIV transmitted drug resistance (TDR). Acute HIV infection (AHI) was the most appropriate time to detect the spread of TDR. In this meta-analysis, our purpose was to evaluate the level of TDR in ART-naive patients with acute/ primary/ early HIV infection, and describe the critical drug-resistant mutations. Methods: We systematically reviewed 1192 studies published between January 1, 2008 and December 30, 2019 in PubMed, Web of Science, Embase, and the Cochrane Library, and selected 12 studies that meet our inclusion criteria. To evaluate the overall prevalence of TDR, we extracted raw data and analyzed prevalence estimates using Stata SE. Estimates of mixed-effects were calculated by random-effects meta-analysis, and the I²statistics were used to estimate the heterogeneity of all included studies.Results: The Data of this meta-analysis come from 12 observational studies, covering 3558 ART-naive individuals with PHI, AHI or EHI. The overall prevalence of HIV-TDR is 9.8% (95% confidence interval (CI): 7.2%–12.3%, p<0.001). Prevalence of resistance by drug class is highest for the NNRTIs at 5.9% (95% CI: 3.1%–8.6%, p<0.001), followed by NRTIs 3.4% (95% CI: 1.8%–5.0%, p<0.001) and PIs 3.4% (95% CI: 2.7%–4.0%, p<0.001). The prevalence of TDR to INIs is 0.3% (95% CI: -0.1%-0.7%, p<0.001), which is the lowest among all antiretroviral drugs.Conclusion: The overall prevalence of TDR is high among AHI patients who have never received ART. This emphasizes the importance of baseline drug resistance testing for public health surveillance and guiding the choice of ART. In addition, the prevalence of TDR to NNRTIs is the highest, while the TDR to INIs is the lowest. This may guide the selection of clinical antiretroviral drugs.

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Viral kinetics in untreated versus treated acute HIV infection in prospective cohort studies in Thailand

Journal of the International AIDS Society ◽

10.7448/ias.20.1.21652 ◽

2017 ◽

Vol 20 (1) ◽

pp. 21652 ◽

Cited By ~ 10

Author(s):

Jintanat Ananworanich ◽

Leigh Anne Eller ◽

Suteeraporn Pinyakorn ◽

Eugene Kroon ◽

Somchai Sriplenchan ◽

...

Keyword(s):

Hiv Infection ◽

Cohort Studies ◽

Prospective Cohort ◽

Viral Kinetics ◽

Acute Hiv Infection ◽

Prospective Cohort Studies ◽

Acute Hiv

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Cohort profile: the Netherlands Cohort Study on Acute HIV infection (NOVA), a prospective cohort study of people with acute or early HIV infection who immediately initiate HIV treatment

BMJ Open ◽

10.1136/bmjopen-2020-048582 ◽

2021 ◽

Vol 11 (11) ◽

pp. e048582

Author(s):

Maartje Dijkstra ◽

Henrieke Prins ◽

Jan M Prins ◽

Peter Reiss ◽

Charles Boucher ◽

...

Keyword(s):

Cohort Study ◽

The Netherlands ◽

Hiv Infection ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Viral Reservoir ◽

Study Group ◽

Hiv Cure ◽

Acute Hiv Infection ◽

Acute Hiv

PurposeInitiation of combination antiretroviral therapy (cART) during acute or early HIV-infection (AEHI) limits the size of the viral reservoir and preserves immune function. This renders individuals who started cART during AEHI promising participants in HIV-cure trials. Therefore, we established a multicentre prospective cohort study in the Netherlands that enrols people with AEHI. In anticipation of future cure trials, we will longitudinally investigate the properties of the viral reservoir size and HIV-specific immune responses among cohort participants.ParticipantsParticipants immediately initiate intensified cART: dolutegravir, emtricitabine/tenofovir and darunavir/ritonavir (DRV/r). After 4 weeks, once baseline resistance data are available, DRV/r is discontinued. Three study groups are assembled based on the preparedness of individuals to participate in the extensiveness of sampling. Participants accepting immediate treatment and follow-up but declining additional sampling are included in study group 1 (‘standard’) and routine diagnostic procedures are performed. Participants willing to undergo blood, leukapheresis and semen sampling are included in study group 2 (‘less invasive’). In study group 3 (‘extended’), additional tissue (gut-associated lymphoid tissue, peripheral lymph node) and cerebrospinal fluid sampling are performed.Findings to dateBetween 2015 and 2020, 140 individuals with AEHI have been enrolled at nine study sites. At enrolment, median age was 36 (IQR 28–47) years, and 134 (95.7%) participants were men. Distribution of Fiebig stages was as follows: Fiebig I, 3 (2.1%); II, 20 (14.3%); III, 7 (5.0%); IV, 49 (35.0%); V, 39 (27.9%); VI, 22 (15.7%). Median plasma HIV RNA was 5.9 (IQR 4.7–6.7) log10 copies/mL and CD4 count 510 (IQR 370–700) cells/mm3. Median time from cART initiation to viral suppression was 8.0 (IQR 4.0–16.0) weeks.Future plansThe Netherlands Cohort Study on Acute HIV infection remains open for participant enrolment and for additional sites to join the network. This cohort provides a unique nationwide platform for conducting future in-depth virological, immunological, host genetic and interventional studies investigating HIV-cure strategies.

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Antiretroviral Therapy for Acute HIV Infection

Case Medical Research ◽

10.31525/ct1-nct03877536 ◽

2019 ◽

Author(s):

Keyword(s):

Antiretroviral Therapy ◽

Hiv Infection ◽

Acute Hiv Infection ◽

Acute Hiv

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Protective HLA alleles are associated with reduced LPS levels in acute HIV infection with implications for immune activation and pathogenesis

PLoS Pathogens ◽

10.1371/journal.ppat.1007981 ◽

2019 ◽

Vol 15 (8) ◽

pp. e1007981 ◽

Cited By ~ 1

Author(s):

Daniel T. Claiborne ◽

Eileen P. Scully ◽

Christine D. Palmer ◽

Jessica L. Prince ◽

Gladys N. Macharia ◽

...

Keyword(s):

Hiv Infection ◽

Immune Activation ◽

Acute Hiv Infection ◽

Hla Alleles ◽

Acute Hiv

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Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018

BMC Infectious Diseases ◽

10.1186/s12879-021-06312-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhen Wang ◽

Bin Zhao ◽

Minghui An ◽

Wei Song ◽

Xue Dong ◽

...

Keyword(s):

Drug Resistance ◽

Hiv Infection ◽

Northeast China ◽

Transmitted Drug Resistance ◽

Newly Diagnosed ◽

Resistance Mutations ◽

Shenyang City ◽

Subtype B ◽

Recent Hiv Infection ◽

Hiv 1

Abstract Background To assess transmitted drug resistance (TDR) to tenofovir (TDF)/emtricitabine (FTC), using as pre-exposure prophylaxis, among newly diagnosed human immunodeficiency virus-1 (HIV-1)-infected residents in Shenyang city, northeast China. Methods Demographic and epidemiological information of all newly diagnosed HIV-1 infected residents in Shenyang city from 2016 to 2018 were anonymously collected from the local HIV epidemic database. HIV-1 pol sequences were amplified from RNA in cryopreserved plasma samples and sequenced directly. Viral subtypes were inferred with phylogenetic analysis and drug resistance mutations (DRMs) were determined according to the Stanford HIVdb algorithm. Recent HIV infection was determined with HIV Limiting Antigen avidity electro immunoassay. Results A total of 2176 sequences (92.4%, 2176/2354) were obtained; 70.9% (1536/2167) were CRF01_AE, followed by CRF07_BC (18.0%, 391/2167), subtype B (4.7%, 102/2167), other subtypes (2.6%, 56/2167), and unique recombinant forms (3.8%, 82/2167). The prevalence of TDR was 4.9% (107/2167), among which, only 0.6% (13/2167) was resistance to TDF/FTC. Most of these subjects had CRF01_AE strains (76.9%, 10/13), were unmarried (76.9%, 10/13), infected through homosexual contact (92.3%, 12/13), and over 30 years old (median age: 33). The TDF/FTC DRMs included K65R (8/13), M184I/V (5/13), and Y115F (2/13). Recent HIV infection accounted for only 23.1% (3/13). Most cases were sporadic in the phylogenetic tree, except two CRF01_AE sequences with K65R (Bootstrap value: 99%). Conclusions The prevalence of TDR to TDF/FTC is low among newly diagnosed HIV-infected cases in Shenyang, suggesting that TDR may have little impact on the protective effect of the ongoing CROPrEP project in Shenyang city.

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