High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients

Hofstra, L. Marije; Rivas, Elena Sánchez; Nijhuis, Monique; Bank, Leonie E.A.; Wilkinson, Eduan; Kelly, Karina; Mudrikova, Tania; Schuurman, Rob; Oliveira, Túlio de; Kort, Jaclyn De; Wensing, Annemarie M. J.

doi:10.1093/cid/cix056

Cited by 13 publications

(9 citation statements)

References 27 publications

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“…K103N was the most common mutation observed in the linked cases, consistent with a study from Aruba, a highly HIV endemic area in the Caribbean. 51 However, unlike the Aruba cluster, where onward transmission of K103N was observed among ART-naive individuals in a large transmission chain, the pattern of small and independent transmission clusters observed here is more suggestive of multiple transmission events from people with ADR on ART.…”

Section: Discussioncontrasting

confidence: 67%

Moderate-to-High Levels of Pretreatment HIV Drug Resistance in KwaZulu-Natal Province, South Africa

Chimukangara

Naidoo

Rhee

et al. 2019

AIDS Research and Human Retroviruses

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There is evidence of increasing levels of pretreatment HIV drug resistance (PDR) in Southern Africa. We used data from two large population-based HIV surveillance studies to estimate prevalence of PDR in KwaZulu-Natal, the province with the highest HIV prevalence in South Africa. Sanger sequencing was performed on samples obtained from a longitudinal HIV surveillance program (study A, 2013-2014) and the HIV Incidence Provincial Surveillance System (study B, 2014-2015). Sequences were included for adult HIV positive participants (age ‡15 years for study A, age 15-49 years for study B) with no documented prior exposure to antiretroviral therapy (ART). Overall and drug class-specific PDR was estimated using the World Health Organization 2009 surveillance drug resistance mutation (SDRM) list, and phylogenetic analysis was performed to establish evidence of drug resistance transmission linkage. A total of 1,845 sequences were analyzed (611 study A; 1,234 study B). An overall PDR prevalence of 9.2% [95% confidence interval (CI) 7.0-11.7] was observed for study A and 11.0% (95% CI 8.9-13.2) for study B. In study B, the prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR exceeded 10% for sequences collected in 2014 (10.2%, 95% CI 7.5-12.9). The most prevalent SDRMs were K103NS (7.5%), M184VI (2.4%), and V106AM (1.4%). There was no evidence of large transmission chains of drug-resistant virus. High level NNRTI PDR (>10%) suggests a need to modify the standard first-line ART regimen and to focus attention on improving the quality of HIV prevention, treatment, and care.

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Section: Discussioncontrasting

confidence: 67%

Moderate-to-High Levels of Pretreatment HIV Drug Resistance in KwaZulu-Natal Province, South Africa

Chimukangara

Naidoo

Rhee

et al. 2019

AIDS Research and Human Retroviruses

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“…Despite neuropsychiatric side effects [46], ART regimens containing EFV demonstrated sustained antiretroviral activity with continued immunologic recovery in the treatment of naïve HIV patients [478]. The frequency of NNRTI-related mutations E138A and K103N were relatively high in this study, which is similar to the findings of other researchers [48, 49]. K103N is a non-polymorphic major NNRTI resistance mutation that can cause high-level resistance to NVP and EFV.…”

Section: Discussionsupporting

confidence: 86%

No Difference in Prevalence of Transmitted Drug Resistance between Injection Drug Users and Non-Injection Drug Users: A Cross-Sectional Study among Antiretroviral Treatment-Naïve HIV Patients

et al. 2018

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Objectives: The epidemiological evidence is inconsistent about whether HIV-positive injection drug users (IDUs) are at higher risk of developing antiretroviral resistance than any other HIV-positive populations. This study aims to investigate and compare transmitted drug resistance (TDR) between IDUs and non-IDUs in Lingshan County, an HIV-hit region in Guangxi, China, where IDU and heterosexual transmission were the two dominant transmission routes and roughly equally contributed to the local HIV transmission. Methods: A cross-sectional study was conducted among newly diagnosed and antiretroviral-treatment (ART)-naïve HIV-1 patients from Lingshan County. The pol gene of HIV-1 from the individuals was sequenced followed by genotyping and TDR analysis. Results: Two dominant transmission routes, heterosexual contact and IDU, accounted for 49.2 and 45.9% of 183 HIV-1 infection cases, respectively. Three genotypes, including CRF08_BC (70.6%), CRF01_AE (24.4%), and CRF07_BC (5.0%), and three unique recombinant forms (1.6%), were identified. There was a significant difference in genotype distribution among the different transmission routes (F = 21.814, p < 0.001). The overall TDR prevalence was 5.5%. There were no significant differences in TDR prevalence among the different transmission routes (F = 1.420, p = 0.439). Conclusions: Injection drug use has little impact on TDR prevalence compared with other routes of transmission.

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“…In developed countries, guidelines recommend baseline genotypic testing in all patients newly diagnosed with HIV infection to ensure the effectiveness of first line ART [6, 7]. Indeed, Hofstra et al demonstrated that in a setting without adequate surveillance, the prevalence of TDRM involving NNRTI resistant HIV can increase to worrisome levels, compromising the efficacy of standard first-line NNRTI-based regimen [8]. Unfortunately, although moderate levels of TDRM have been reported in Brazil [9–14], ranging from 3.8% in Maranhão [10] to 13.9% in São Paulo [12], the genotyping test is not available for most treatment-naïve patients [15].…”

Section: Introductionmentioning

confidence: 99%

Moderate prevalence of HIV-1 transmitted drug resistance mutations in southern Brazil

Bahls¹,

Canezin²,

Reiche³

et al. 2019

AIDS Res Ther

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BackgroundDespite the advances in therapy, the occurrence of drug-resistant human immunodeficiency virus type 1 (HIV-1) is a major obstacle to successful treatment. This study aimed to characterize the genetic diversity and to determine the prevalence of transmitted drug resistance mutations (TDRM) between individuals recently or chronically diagnosed with HIV-1 from Paraná, Brazil.MethodsA total of 260 HIV-1 positive antiretroviral therapy-naïve patients were recruited to participate on the study, of which 39 were recently diagnosed. HIV-1 genotyping was performed using sequencing reaction followed by phylogenetic analyses to determine the HIV-1 subtype. TDRM were defined using the Calibrated Population Resistance Tool program.ResultsThe HIV-1 subtypes frequency found in the studied population were 54.0% of subtype B, 26.7% subtype C, 6.7% subtype F1 and 12.7% recombinant forms. The overall prevalence of TDRM was 6.7%, including 13.3% for recently diagnosed subjects and 5.9% for the chronic group.ConclusionsThe prevalence of resistance mutations found in this study is considered moderate, thus to perform genotyping tests before the initiation of antiretroviral therapy may be important to define the first line therapy and contribute for the improvement of regional prevention strategies for epidemic control.Electronic supplementary materialThe online version of this article (10.1186/s12981-019-0219-1) contains supplementary material, which is available to authorized users.

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High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients

Abstract: SummaryThe prevalence of resistant HIV in Aruba has increased to alarming levels, compromising the WHO-recommended first-line regimen. As adequate surveillance as advocated by the WHO is limited, the Caribbean region could face an unidentified rise of NNRTI-resistant HIV.

Cited by 13 publications

References 27 publications

Moderate-to-High Levels of Pretreatment HIV Drug Resistance in KwaZulu-Natal Province, South Africa

Moderate-to-High Levels of Pretreatment HIV Drug Resistance in KwaZulu-Natal Province, South Africa

No Difference in Prevalence of Transmitted Drug Resistance between Injection Drug Users and Non-Injection Drug Users: A Cross-Sectional Study among Antiretroviral Treatment-Naïve HIV Patients

Moderate prevalence of HIV-1 transmitted drug resistance mutations in southern Brazil

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