HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province, China, 2014-2020 / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China.@*METHODS@#A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database.@*RESULTS@#A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs.@*CONCLUSION@#The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

High Frequency of Non-B Human Immunodeficiency Virus Type 1 (HIV-1) Subtype Specific Mutations at the Protease Gene among Treatment-naive HIV-1 Infected Individuals in Jos, Nigeria.

Aims: To determine the prevalence of non-B HIV-1 subtype specific mutations in the protease gene among antiretroviral drug-naive individuals in Jos, Nigeria. Study Design: This was a cross-sectional study in which randomly selected blood samples of HIV-1 positive anti-retroviral drug-naïve individuals were used for genotyping assay. Place and Duration of Study: The study was conducted at the adult HIV clinic of the AIDS Prevention Initiative in Nigeria (APIN) programme, Jos University Teaching Hospital (JUTH), Jos, Nigeria between October 2010 and April 2011. Methodology: Of the one hundred and five plasma samples, 100 samples were successfully reverse transcribed and amplified by nested PCR. The amplicons were directly sequenced on an automated ABI genetic analyzer using BigDye Terminator Cycle Sequencing Kit. Subtyping and phylogenetic analyses were performed using the REGA subtyping tool version 2.0 and MEGA 5.0 software. Both the Stanford HIV database algorithm and IAS-USA 2013 drug resistance update were used for interpretation of drug sensitivity. Results: The proportion of the non-B HIV-1 subtypes were as follows: CRF02_AG (48%), G (41%), CRF06_cpx (6%), A (5%). Q58E, a major drug resistance mutation to PI, occurred as a low prevalence mutation in subtype G. The most common mutations observed among the subtypes were I13V, K14R, K20I, M36I, R41K, H69K, V82I and L89M. Conclusion: A non-uniform distribution of non-B HIV-1 subtypes were observed in Jos, Nigeria, with CRF02_AG and G predominating among the antiretroviral drug-naive individuals. Among the different subtypes in circulation, there was a high prevalence of minor mutations and natural polymorphisms associated with the protease gene. Such mutations define the subtype diversity which may impact on virulence and drug ‘responses’, thus further studies are needed to evaluate the clinical implications of these mutations.

Genetic architecture of HIV-1 genes circulating in north India & their functional implications.

This review presents data on genetic and functional analysis of some of the HIV-1 genes derived from HIV-1 infected individuals from north India (Delhi, Punjab and Chandigarh). We found evidence of novel B/C recombinants in HIV-1 LTR region showing relatedness to China/Mynmar with 3 copies of Nfκb sites; B/C/D mosaic genomes for HIV-1 Vpr and novel B/C Tat. We reported appearance of a complex recombinant form CRF_02AG of HIV-1 envelope sequences which is predominantly found in Central/Western Africa. Also one Indian HIV-1 envelope subtype C sequence suggested exclusive CXCR4 co-receptor usage. This extensive recombination, which is observed in about 10 per cent HIV-1 infected individuals in the Vpr genes, resulted in remarkably altered functions when compared with prototype subtype B Vpr. The Vpu C was found to be more potent in causing apoptosis when compared with Vpu B when analyzed for subG1 DNA content. The functional implications of these changes as well as in other genes of HIV-1 are discussed in detail with possible implications for subtype-specific pathogenesis highlighted.

Study of HIV-1 subtypes in serodiscordant couples attending an integrated counselling and testing centre in Mumbai using heteroduplex mobility analysis and DNA sequencing.

Aims: To determine the prevalent subtypes of HIV-1 in serodiscordant couples. Setting: Integrated Counselling and Testing Centre (ICTC), Department of Microbiology. Study Design: Prospective pilot study. Participants: Thirty HIV-1 serodiscordant couples. Inclusion Criteria: a) Documentation of HIV-1 infection in one partner and seronegative status in the other, current history of continued unprotected sexual activity within the partnership, demonstration that they have been in a partnership for at least 1 year and are not currently on highly active antiretroviral therapy HAART; b) willingness of both partners to provide written informed consent including consent to continued couple counselling for 3 months. Materials and Methods: HIV-1 subtyping was carried out by heteroduplex mobility analysis (HMA) by amplifying env region; and DNA sequencing by amplifying gag region. Results: HIV-1 env gene was amplified successfully in 10/30 samples; gag gene, in 25/30 samples; and both env and gag gene were amplified successfully in 5/30 samples. HIV-1 subtype C was detected from 21 samples; subtype B, from 7; and subtype A, from 2. Sample from 1 positive partner was detected as subtype C by env HMA and subtype B by gag sequencing. Conclusion: HIV-1 subtype C was found to be the predominant subtype of HIV-1 in serodiscordant couples attending our ICTC, followed by HIV-1 subtype B and HIV-1 subtype A, respectively. DNA sequencing was found to be the most reliable method for determining the subtypes of HIV-1.

Genetic diversity of human immunodeficiency virus-1 isolates in Paraná, Brazil

OBJECTIVE: Because epidemiological data on circulating HIV subtypes among HIV-positive patients in the state of Paraná were not known until now, the aims of this study were to describe the genetic diversity profile of HIV-1 in treated patients in Paraná, Brazil, and report the differences in protease (PR) and reverse transcriptase (RT) mutations in HIV-1 subtypes. PATIENTS AND METHODS: A cross-sectional study was conducted from 2003 to 2006. Plasma viral RNA of 389 patients was extracted and PR and RT genes were polymerase chain reaction-amplified and sequenced. Sequences were subtyped and examined for antiretroviral resistance mutations. Data on gender of patient harboring the viruses and past history of antiretroviral treatment were also collected. RESULTS: Most viruses were either subtype B (61.44 percent) or subtype C (20.57 percent). Subtype C and F were more frequent in women (p < 0.00). The prevalence of subtypes was similar over the years studied. The most frequent RT mutations in all subtypes were M184V and mutations at codons 215, 41, 103, 67, 219, and 190. Mutations 41L, 210W, 215YF, and 74V were significantly more prevalent on subtype B, and the mutation 106M was significantly more prevalent on subtype C. The most frequent major PI mutations in all subtypes occurred at codons 46, 82, and 90. PR mutations 32I, 46I, and 84V were significantly more prevalent on subtype B. The minor PI mutations on codons 36, 93, and 63 were more prevalent on subtypes F, C, and B, respectively. CONCLUSION: We concluded that the predominant strain of HIV-1 in Paraná is subtype B, followed by subtype C. Some mutations at PR and TR had subtype predominance in accordance with other authors' report.

High prevalence and association of HIV-1 non-B subtype with specific sexual transmission risk among antiretroviral naïve patients in Porto Alegre, RS, Brazil / Alta prevalência e associação do subtipo não-B do vírus HIV-1 com risco específico de transmissão sexual entre pacientes virgens de tratamento antirretroviral em Porto Alegre, Brasil

In South Brazil the circulation of two HIV-1 subtypes with different characteristics represents an important scenario for the study of the impact of HIV-1 diversity on the evolution of the HIV-1 epidemic and AIDS disease. HIV-1 B, the predominant variant in industrialized countries and HIV-1 C, the most prevalent subtype in areas with rapid epidemic growth, are implicated in most infections. We evaluated blood samples from 128 antiretroviral (ARV) naïve patients recruited at entry to the largest HIV outpatient service in Porto Alegre. Based on partial pol region sequencing, HIV-1 C was observed in 29 percent, HIV-1 B in 22.6 percent and, the recently identified CRF31_BC, in 23.4 percent of 128 volunteers. Other variants were HIV-1 F in 10 percent and other mosaics in 5.5 percent. In order to evaluate the association of socio-behavioral characteristics and HIV-1 subtypes, interviews and laboratory evaluation were performed at entry. Our data suggest an established epidemic of the three major variants, without any evidence of partitioning in either of the subgroups analyzed. However, anal sex practices were associated with subtype B, which could indicate a greater transmissibility of non-B variants by vaginal intercourse. This study provides baseline information for epidemiologic surveillance of the changes of the molecular characteristics of HIV-1 epidemics in this region.

No sul do Brasil a circulação de dois subtipos de HIV-1 com características diferentes representa importante cenário para o estudo do impacto da diversidade do HIV-1 na evolução da epidemia e na AIDS. O HIV-1 B, variante predominante nos países industrializados e o HIV-1 C, o subtipo mais prevalente em áreas com maiores taxas de crescimento da epidemia, estão implicados na maioria das infecções. Avaliamos amostras de sangue de 128 pacientes sem exposição a antirretrovirais, recrutados ao ingressarem no maior serviço ambulatorial de HIV/AIDS de Porto Alegre. Com base no sequenciamento parcial da região pol, o HIV-1 C foi observado em 29 por cento, HIV-1 B em 22,6 por cento e uma forma recombinante recentemente descrita, CRF31_BC, foi observada em 23,4 por cento entre 128 voluntários. Outras variantes encontradas foram HIV-1 F em 10 por cento e outros mosaicos em 5,5 por cento. Para avaliar associações entre características sócio-comportamentais e subtipos do HIV-1 foram realizadas entrevistas e exames laboratoriais na entrada do estudo. Nossos dados sugerem uma epidemia estabelecida dessas três variantes principais, sem evidência de compartilhamento em nenhum subgrupo analisado. Entretanto, prática sexual anal se mostrou associada à transmissão de subtipo B, o que pode indicar maior transmissibilidade das variantes não-B por intercurso vaginal. Este estudo permite delinear uma linha de base para o monitoramento epidemiológico das mudanças nas características moleculares da epidemia do HIV-1 nesta região.