Faculty Opinions recommendation of Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load.

Abstract Background South Africa, with one of the highest HIV prevalences in the world, introduced the universal test and treat (UTT) programme in September 2016. Barriers to sustained viral suppression may include drug resistance in the pre-treated population, non-adherence, acquired resistance; pharmacokinetics and pharmacodynamics, and concurrent use of alternative treatments. Objective The purpose of this review is to highlight potential challenges to achieving sustained viral load suppression in South Africa (SA), a major expectation of the UTT initiative. Methodology Through the PRISMA approach, published articles from South Africa on transmitted drug resistance; adherence to ARV; host genetic factors in drug pharmacokinetics and pharmacodynamics, and interactions between ARV and herbal medicine were searched and reviewed. Results The level of drug resistance in the pre-treated population in South Africa has increased over the years, although it is heterogeneous across and within Provinces. At least one study has documented a pre-treated population with moderate (> 5%) or high (> 15%) levels of drug resistance in eight of the nine Provinces. The concurrent use of ARV and medicinal herbal preparation is fairly common in SA, and may be impacting negatively on adherence to ARV. Only few studies have investigated the association between the genetically diverse South African population and pharmacokinetics and pharmacodynamics of ARVs. Conclusion The increasing levels of drug resistant viruses in the pre-treated population poses a threat to viral load suppression and the sustainability of first line regimens. Drug resistance surveillance systems to track the emergence of resistant viruses, study the burden of prior exposure to ARV and the parallel use of alternative medicines, with the goal of minimizing resistance development and virologic failure are proposed for all the Provinces of South Africa. Optimal management of the different drivers of drug resistance in the pre-treated population, non-adherence, and acquired drug resistance will be beneficial in ensuring sustained viral suppression in at least 90% of those on treatment, a key component of the 90-90-90 strategy.

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1282. Detection of HIV Transmitted Drug Resistance by Next-Generation Sequencing in a CRF01_AE Predominant Epidemic

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1115 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S391-S391 ◽

Cited By ~ 1

Author(s):

Edsel Maurice Salvana ◽

Nina Dungca ◽

Geraldine Arevalo ◽

Katerina Leyritana ◽

Christian Francisco ◽

...

Keyword(s):

Drug Resistance ◽

Viral Load ◽

Next Generation Sequencing ◽

The Philippines ◽

Cd4 Count ◽

Asia Pacific ◽

Transmitted Drug Resistance ◽

Next Generation ◽

Hiv Drug Resistance ◽

Generation Sequencing

Abstract Background The Philippines has the fastest growing HIV epidemic in the Asia-Pacific. Concurrent with this is a subtype shift from B to CRF01_AE. We have previously documented transmitted drug resistance (TDR) locally. However, the lack of drug pressure and the insensitivity of Sanger-based sequencing (SBS) may leave archived drug-resistance mutations (DRMs) undetected. To better detect TDR, we performed next-generation sequencing (NGS) on treatment-naïve patients and compared this with SBS. Methods Following ethics approval, newly-diagnosed adult Filipino HIV patients were recruited from the Philippine General Hospital HIV treatment hub. Demographic data were collected, and blood samples underwent SBS with a WHO-approved protocol. Whole-genome NGS was performed using Illumina HiSeq through a commercial provider (Macrogen, Korea). Genotype and DRMs were analyzed and scored using the Stanford HIV Drug Resistance Database. Results 113 patients were analyzed. Median age was 29 years (range 19–68), mean CD4 count was 147 cells/µL (range 0–556) and median viral load was 2.8 × 106 copies/mL. Genotype distribution was: CRF01_AE (93), B (13), possible CRF01_AE/B recombinants (5), CRF02_AG (1), possible URF (1). TDR prevalence by SBS and NGS at different minority variant cutoffs are shown in Table 1. All DRMs on SBS were found on NGS. Some samples had multiple DRMs. No factors were significantly associated with TDR, genotype, viral load or baseline CD4 count. Conclusion NGS is a more sensitive tool for detecting TDR compared with SBS. Nearly double the DRMs were found at an NGS cutoff of ≥5%, including INSTI DRMs. With increasing HIV drug resistance worldwide, switching to NGS may help decrease rates of initial treatment failure, especially in settings with limited repertoires of ARVs. Disclosures All authors: No reported disclosures.

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The Frequency of HIV-1 Infection in Iranian Children and Determination of the Transmitted Drug Resistance in Treatment-Naïve Children

Current HIV Research ◽

10.2174/1570162x17666191106111211 ◽

2020 ◽

Vol 17 (6) ◽

pp. 397-407

Author(s):

Maryam Jarchi ◽

Farah Bokharaei-Salim ◽

Maryam Esghaei ◽

Seyed Jalal Kiani ◽

Fatemeh Jahanbakhsh ◽

...

Keyword(s):

Drug Resistance ◽

Pediatric Patients ◽

Phylogenetic Analyses ◽

Rna Extraction ◽

Transmitted Drug Resistance ◽

The Arts ◽

Treatment Naïve ◽

Iranian Children ◽

Hiv 1

Background: The advent of resistance-associated mutations in HIV-1 is a barrier to the success of the ARTs. Objective: In this study, the abundance of HIV-1 infection in Iranian children, and also detection of the TDR in naïve HIV-1 infected pediatric (under 12 years old) were evaluated. Materials: From June 2014 to January 2019, a total of 544 consecutive treatment-naïve HIV-1- infected individuals enrolled in this study. After RNA extraction, amplification, and sequencing of the HIV-1 pol gene, the DRM and phylogenetic analysis were successfully performed on the plasma specimens of the ART-naïve HIV-1-infected-children under 12 years old. The DRMs were recognized using the Stanford HIV Drug Resistance Database. Results: Out of the 544 evaluated treatment-naïve HIV-1-infected individuals, 15 (2.8%) cases were children under 12 years old. The phylogenetic analyses of the amplified region of pol gene indicated that all of the 15 HIV-1-infected pediatric patients were infected by CRF35_AD, and a total of 13.3% (2/15) of these children were infected with HIV-1 variants with SDRMs (one child harbored two related SDRMs [D67N, V179F], and another child had three related SDRMs [M184V, T215F, and K103N]), according to the last algorithm of the WHO. No PIs-related SDRMs were observed in HIV-1-infected children. Conclusion: The current study demonstrated that a total of 13.3% of treatment-naïve HIV-1-infected Iranian pediatrics (under 12 years old) were infected with HIV-1 variants with SDRMs. Therefore, it seems that screening to recognize resistance-associated mutations before the initiation of ARTs among Iranian children is essential for favorable medication efficacy and dependable prognosis.

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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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HIV‐1 genetic diversity and transmitted drug resistance among newly diagnosed HIV‐1 individuals in Jiangmen, China

Journal of Medical Virology ◽

10.1002/jmv.25741 ◽

2020 ◽

Vol 92 (12) ◽

pp. 3209-3218

Author(s):

Xin Guan ◽

Min Han ◽

Zhiju Li ◽

Lihua Wang ◽

Donghe Zhang ◽

...

Keyword(s):

Genetic Diversity ◽

Drug Resistance ◽

Transmitted Drug Resistance ◽

Newly Diagnosed ◽

Hiv 1

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Rates and Correlates of Short Term Virologic Response among Treatment-Naïve HIV-Infected Children Initiating Antiretroviral Therapy in Ethiopia: A Multi-Center Prospective Cohort Study

Pathogens ◽

10.3390/pathogens8040161 ◽

2019 ◽

Vol 8 (4) ◽

pp. 161

Author(s):

Birkneh Tilahun Tadesse ◽

Adugna Chala ◽

Jackson Mukonzo ◽

Tolosssa Eticha Chaka ◽

Sintayehu Tadesse ◽

...

Keyword(s):

Drug Resistance ◽

Viral Load ◽

Plasma Viral Load ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Virological Suppression ◽

Virologic Suppression ◽

Hiv Drug Resistance ◽

Treatment Naïve ◽

The Impact

There is limited data on virologic outcome and its correlates among HIV-infected children in resource-limited settings. We investigated rate and correlates of virologic outcome among treatment naïve HIV-infected Ethiopian children initiating cART, and were followed prospectively at baseline, 8, 12, 24 and 48 weeks using plasma viral load, clinical examination, laboratory tests and pretreatment HIV drug resistance (PDR) screening. Virologic outcome was assessed using two endpoints–virological suppression defined as having “undetectable” plasma viral load < 150 RNA copies/mL, and rebound defined as viral load ≥150 copies/mL after achieving suppression. Cox Proportional Hazards Regression was employed to assess correlates of outcome. At the end of follow up, virologic outcome was measured for 110 participants. Overall, 94(85.5%) achieved virological suppression, of which 36(38.3%) experienced virologic rebound. At 48 weeks, 9(8.2%) children developed WHO-defined virological treatment failure. Taking tenofovir-containing regimen (Hazard Ratio (HR) 3.1-[95% confidence interval (95%CI) 1.0–9.6], p = 0.049) and absence of pretreatment HIV drug resistance (HR 11.7-[95%CI 1.3–104.2], p = 0.028) were independently associated with earlier virologic suppression. In conclusion, PDR and cART regimen type correlate with rate of virologic suppression which was prominent during the first year of cART initiation. However, the impact of viral rebound in 38.3% of the children needs evaluation.

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