Identification of a novel HIV-1 third-generation circulating recombinant form (CRF126_0755) in Guangdong, China.

The genetic recombination patterns and genetic distribution of HIV-1 are valuable for elucidating the epidemic and genetic diversity of HIV. Numerous HIV-1 circulating recombinant forms (CRFs) have recently emerged and disseminated rapidly. In China, at least 32 CRFs have been reported to account for more than 80% of all HIV infections. However, CRFs derived from the CRF07_BC and CRF55_01B lineages have never been recorded. Here, a novel third-generation CRF involving HIV-1 was identified in four HIV-1-infected patients in Guangdong, China, who had no epidemiological association with each other. Phylogenetic and recombinant analyses confirmed that these strains shared highly similar recombination patterns, with the CRF07_BC backbone substituted by a CRF55_01B segment; therefore, these strains were classified as CRF126_0755. This is the first study of a CRF derived from CRF07_BC and CRF55_01B. Bayesian phylogenetic inference suggested that CRF126_0755 originated in approximately 2005-2007. The present findings reveal that the genotype composition of HIV-1 has become more complex than that of other viruses and highlight the urgent need for continuous molecular screening and epidemic surveillance within HIV-1-infected populations to advance our understanding of viral transmission mechanisms.

Immunogenicity and safety of inactivated SARS-CoV-2 vaccines in people living with HIV: A longitudinal cohort study.

To clarify the characteristics in immunogenicity and safety of inactivated SARS-Cov-2 vaccines among HIV-infected individuals, a longitudinal cohort study was performed on HIV-infected and HIV-uninfected participants with no history of COVID-19 infection and COVID-19 vaccine inoculation. Participants information and adverse events were collected. Blood samples were collected on the same day before vaccination, 21 days after the first shot, 28 days after the second shot, 6 months after the second vaccination and 14 days after the third dose to test anti-receptor-binding domain IgG antibody, viral load, CD4+, CD8+ T cell count. Our result showed that although HIV-infected adults with low nadir CD4+ T cell count ≤ 350 cells/mm3 generate significantly lower immune response after three shots of vaccine compared with HIV-negative controls, 100% of all the HIV-infected and healthy controls were seroconverted after the third shot. Seroconversion ratio and antibody level of 190 days after two shots of vaccination for HIV-infected with nadir CD4+ T cell count ≤ 350 were significantly lower than that of healthy controls. No significant difference was found in viral load among blood samples collected at each time points. CD4 and CD4/CD8 ratio value were found increased greatly after each shot of inoculation in HIV-infected individuals with nadir CD4+ T cell count ≤ 350. Multiple logistic regression analysis showed that among HIV-infected individuals, PLWH with CD4+ T cell count ≤ 350 were less likely experience seroconversion 21 days after the first shot, and less likely maintained antibody immunity 6 months post 2nd dose. Adverse events after each inoculation were not serious and recovered within 1 week. In conclusion, inactivated COVID-19 vaccine was safe and effective in people living with HIV after three shots of vaccination. HIV-infected individuals with low nadir CD4+ T cell count ≤ 350 was associated with a nonoptimal antibody response. Further vaccination strategies could be developed for those with low CD4+ T cell counts.

Genetic characteristics of a novel HIV-1 recombinant lineage (CRF103_01B) and its prevalence in northern China.

During the routine surveillance of HIV-1 pretreatment drug resistance in Beijing, five men who have sex with men (MSM) and a woman were observed to get infected by newly identified CRF103_01B strain. To elucidate the genetic characteristics, the near full-length genome (NFLG) was obtained. Phylogenetic inference indicated that CRF103_01B NFLG was composed of six mosaic segments. Segments IV and V of CRF103_01B were located among the clusters subtype B and CRF01_AE (group 5), respectively. The CRF103_01B strain was deduced to originate from Beijing MSM population around 2002.3-2006.4 and continued to spread among MSM population at a low level, then to the general population via heterosexual contact in northern China. Molecular epidemiology surveillance of CRF103_01B should be reinforced.

Characteristics of drug resistance in HIV-1 CRF55_01B from ART-experienced patients in Guangdong, China.

BACKGROUND: HIV-1 acquired drug resistance (ADR) has become a critical clinical and public health issue. Recently, HIV-1 CRF55_01B has been found more frequently in the MSM population. OBJECTIVE: To investigate the characteristics of HIV-1 drug resistance mutations (DRMs) and the extent of changes in drug susceptibility among ART-experienced CRF55_01B-infected adults of Guangdong. METHODS: ADR was tested for immediately in CRF55_01B-infected patients with virological failure. Demographic and epidemiological information was collected. DRMs and antiretroviral susceptibility were interpreted using the Stanford University HIV Drug Resistance Database HIVdb program. RESULTS: Overall, 162 (4.78%) CRF55_01B isolates were identified from 2013 to 2018. Among DRMs, M184V (43.83%) was the most frequent NRTI DRM, followed by K65R (23.46%), and V179E (98.77%) was the most frequent NNRTI DRM, followed by K103N (47.53%) and Y181C (14.81%). According to the HIVdb program, 79.01% of the CRF55_01B-infected patients carried mutations conferring low-level or higher drug resistance to any of the three classes of ART drugs. Among PI DRMs, only one mutation affording low-level resistance to nelfinavir was found (0.62%). Among NRTI DRMs, a high proportion of high-level resistance to lamivudine (58.64%) and emtricitabine (58.02%) was found. As regards NNRTIs, more than 75% of patients carried efavirenz and nevirapine DRMs. The percentages of high-level resistance were 70.99%, 63.58%, 22.22%, 17.90% and 4.32% for nevirapine, efavirenz, rilpivirine, doravirine and etravirine, respectively. CONCLUSIONS: High frequencies of DRMs and resistance were observed among CRF55_01B-infected patients failing ART in Guangdong, and interventions may be considered to minimize ecological contributions to ART.

Detection of pretreatment minority HIV-1 reverse transcriptase inhibitor-resistant variants by ultra-deep sequencing has a limited impact on virological outcomes.

OBJECTIVES: Ultra-deep sequencing (UDS) is a powerful tool for exploring the impact on virological outcome of minority variants with low frequencies, some even <1% of the virus population. Here, we compared HIV-1 minority variants at baseline, through plasma RNA and PBMC DNA analyses, and the dominant variants at the virological failure (VF) point, to evaluate the impact of minority drug-resistant variants (MDRVs) on virological outcomes. METHODS: Single-molecule real-time sequencing (SMRTS) was performed on baseline RNA and DNA. The Stanford HIV-1 drug resistance database was used for the identification and evaluation of drug resistance-associated mutations (DRAMs). RESULTS: We classified 50 patients into virological success (VS) and VF groups. We found that the rates of reverse transcriptase inhibitor (RTI) DRAMs determined by SMRTS did not differ significantly within or between groups, whether based on RNA or DNA analyses. There was no significant difference in the level of resistance to specific drugs between groups, in either DNA or RNA analyses, except for the DNA-based analysis of lamivudine, for which there was a trend towards a higher prevalence of intermediate/high-level resistance in the VF group. The RNA MDRVs corresponded to DNA MDRVs, except for M100I and Y188H. Sequencing from DNA appeared to be more sensitive than from RNA to detect MDRVs. CONCLUSIONS: Detection of pretreatment minority HIV-1 RTI-resistant variants by UDS showed that MDRVs at baseline were not significantly associated with virological outcome. However, HIV-1 DNA sequencing by UDS was useful for detecting pretreatment drug resistance mutations in patients, potentially affecting virological responses, suggesting a potential clinical relevance for ultra-deep DNA sequencing.

Risk Prediction Score for HIV Infection: Development and Internal Validation with Cross-Sectional Data from Men Who Have Sex with Men in China.

Receptive anal intercourse, multiple partners, condomless sex, sexually transmitted infections (STIs), and drug/alcohol addiction are familiar factors that correlate with increased human immunodeficiency virus (HIV) risk among men who have sex with men (MSM). To improve estimation to HIV acquisition, we created a composite score using questions from routine survey of 3588 MSM in Beijing, China. The HIV prevalence was 13.4%. A risk scoring tool using penalized maximum likelihood multivariable logistic regression modeling was developed, deploying backward step-down variable selection to obtain a reduced-form model. The full penalized model included 19 sexual predictors, while the reduced-form model had 12 predictors. Both models calibrated well; bootstrap-corrected c-indices were 0.70 (full model) and 0.71 (reduced-form model). Non-Beijing residence, short-term living in Beijing, illegal drug use, multiple male sexual partners, receptive anal sex, inconsistent condom use, alcohol consumption before sex, and syphilis infection were the strongest predictors of HIV infection. Discriminating higher-risk MSM for targeted HIV prevention programming using a validated risk score could improve the efficiency of resource deployment for educational and risk reduction programs. A valid risk score can also identify higher risk persons into prevention and vaccine clinical trials, which would improve trial cost-efficiency.

[Analysis on factors associated with taking subsequent confirmation test among men who have sex with men after being tested positive in oral fluid HIV antibody test in Beijing].

OBJECTIVE: To analyze the proportion and associated factors of taking subsequent confirmation test among men who have sex with men (MSM) after being tested positive in oral fluid HIV antibody test. METHODS: By using successive sampling, 1 003 MSM, who were tested positive in oral fluid HIV antibody test in China-Bill & Melinda Gates Foundation AIDS prevention Program (Extension program) in Beijing during May 1 to December 31, 2013, were recruited. The inclusion criteria included: the objects were men who reported having sex with men; the objects aged more than 18 years old; the objects were tested positive in oral fluid HIV antibody test; the objects had not been reported as HIV positives in China Information System for Disease Control and Prevention previously. According to the program strategy, MSM grassroots organizations transferred the respondents to seek subsequent confirmation tests in specific Center for Disease Control and Prevention (CDCs) or hospitals. The subsequent confirmation tests included: fingertip blood HIV antibody rapid test, venous blood Enzyme Linked Immunosorbent Assay (ELISA) HIV antibody test and venous blood Western Blot (WB) HIV antibody test. Chi-square test was adopted to compare the proportion of taking subsequent confirmation tests in different groups. Nonconditional multivaritae binarylogistic regression analysis was taken to identify the associated factors with whether taking subsequent confirmation tests and to calculate the OR (95% CI) values. RESULTS: The 1 003 respondents were (30.9 ± 9.1) years old. Among all objects, 87.8% (881/1 003) of them took fingertip blood HIV antibody rapid tests and the positive rate was 85.4% (752/881). 98.0% (737/752) of those who were identified as positive in fingertip blood HIV rapid tests took ELISA and WB tests, and the positive rate was 94.4% (696/737). Comparing with those who were expected to seek subsequent confirmation tests in CDCs, the OR (95% CI) value of those who were expected to seek tests in hospitals was 5.10 (1.69-15.36). The OR (95% CI) values of those who used condom sometimes and those who never used condom in anal sex were 5.81 (2.14-15.77) and 3.45 (2.00-5.97) respectively, in comparison with those who reported not having anal sex or using condom consistently in anal sex during the past 6 months. Comparing with the respondents recruited from the internet, the OR (95% CI) values of those recruited in bathrooms, parks/toilets and bars were 0.17 (0.05-0.53), 0.10 (0.04-0.29) and 0.22 (0.06-0.79) respectively. The likelihood of taking subsequent confirmation test decreased with the increase of number of male sexual partners in the past 3 months, and the OR (95% CI) value was 0.92 (0.86-0.99). CONCLUSION: The potential HIV positive MSM in the bathroom, park/toilet and bars are less likely to take subsequent confirmation test. Those who do not use condom consistently during anal sex are more likely to seek subsequent confirmation test. Medical organization conducting subsequent confirmation tests is more likely to increase the confirmation test rate of potential HIV positive MSM. The number of male sexual partners has negative correlation with whether to accept the subsequent confirmation test.

Trends of subtype variation of human immunodeficiency virus type 1 in Zhejiang Province, China.

The epidemic characteristics of human immunodeficiency virus type 1 (HIV-1) in Zhejiang Province have not been systematically identified. This study presented a dynamic analysis of HIV-1 subtype variation in Zhejiang from 2004 to 2008, based on the surveillance of molecular epidemiology or drug resistance. CRF01_AE was the major strain (43.5 %) spreading across the province, second by B/B' (17.9 %), CRF07_BC (17.1 %), and CRF08_BC (13.7 %). The strains were mainly transmitted by heterosexual contact. Novel recombinant strains and vertical transmission were occasionally reported. Floating population from other provinces accounted for a significant number of HIV-1 cases in Zhejiang. These data may provide us rational intervention strategy for further control of HIV dissemination.

Molecular genetic characterization analysis of a novel HIV-1 circulating recombinant form (CRF156_0755) in Guangdong, China.

Introduction: The characteristic of human immunodeficiency virus type 1 (HIV-1) is its susceptibility to erroneous replication and recombination, which plays a crucial role in the diverse and dynamic variation of HIV-1. The spread of different subtypes in the same population often leads to the emergence of circulating recombination forms (CRFs). At present, the main recombinant subtypes of HIV-1 in China are CRF07_BC, CRF01_AE, CRF08_BC and B' subtypes, while CRF55_01B has become the fifth major epidemic strain in China after rapid growth in recent years since it was first reported in 2013. In this study, we obtained five nearly full-length genomes (NFLGs) and one half-length genome from five different cities in Guangdong. Here, we focused on analyzing their characteristics, parental origin and drug resistance. Methods: Plasma samples were collected from six HIV-1 infected patients in Guangdong Province who had no epidemiological association with each other. The NFLGs of HIV-1 were amplified in two overlapping segments by the near-terminal dilution method. The positive products were sequenced directly to obtain genomic sequences. The recombinant patterns and breakpoints of the NFLGs were determined using the Simplot software and confirmed by the maximum likelihood trees for segments using the IQ-TREE and BEAST software. The genotypic resistance profiles of the protease reverse transcriptase and integrase were resolved by the Stanford HIV drug resistance database. Results: The six genomes shared highly similar recombinant pattern, with the CRF55_01B backbone substituted by CRF07_BC segments, therefore assigned as CRF156_0755. The evolutionary analysis of the segments showed that CRF07_BC segments were not clustered with the Chinese MSM variants in the CRF07_BC lineage. All the five NFLGs were identified with the non-nucleoside reverse-transcription inhibitors (NNRTIs) resistance mutation V179E. Discussion: With the accumulation and evolution of recombination between CRF55_01B and CRF 07_BC, the prevalence of more recombinant strains of CRF55_01B and CRF 07_BC may occur. Therefore, it is necessary to strengthen the identification and monitoring of the recombination of CRF55_01B and CRF 07_BC.

Genetic characteristics of a novel HIV-1 circulating recombinant form (CRF128_07B) identified among MSM in Guangdong Province, China.

OBJECTIVE: To obtain and investigate the genetic characteristics of four HIV-1 near full-length genome sequences (NFLGs), aiming at a description of a novel circulating recombinant form (CRF) in Guangdong China. METHODS: Plasma samples were collected from HIV-1 infected MSM patients in Guangdong Province who had no epidemiological association with each other. The NFLGs were amplified with two overlapping halves and phylogenetic analyses were performed using Mega V11.0.1. Recombination analyses were comprehensively screened with the jpHMM, RIP, and BootScan analyses. Finally, the Bayesian phylogenetic analyses were performed using Beast V1.10.4 to estimate the origin time. RESULTS: Phylogenetic analyses revealed the four NFLGs formed a distinct monophyletic cluster distinguished from other known subtypes in the Neighbor-joining tree. Recombinant analyses revealed they shared a highly similar recombinant pattern, with the CRF07_BC backbone substituted by three subtype B segments. Subregion phylogenetic analyses confirmed them to be a novel CRF composed of CRF07_BC and subtype B, therefore, designed as CRF128_07B. According to the Bayesian phylogenetic analyses, CRF128_07B was inferred to approximately originated around 2005-2006. CONCLUSIONS: These findings described a novel HIV-1 CRF identified from MSM in Guangdong Province. This is the first detection of a CRF comprising CRF07_BC and subtype B. The present finding highlights the urgent need for continuous molecular screening and the epidemic surveillance within the MSM populations.

[Molecular epidemiological characteristics of HIV-1 B'/C strains in Beijing].

OBJECTIVE: To analyze the molecular epidemiological characteristic of HIV-1 B'/C strains prevalent in Beijing. METHODS: Plasma samples were collected from 200 newly diagnosed HIV-1 B'/C individuals reported during 2006 to 2010 in Beijing. The gag gene fragments were amplified from RNA template extracted from plasma with reverse transcription (RT) and nested polymerase chain reaction (PCR). And the sequences were analyzed by phylogenetic methods and Entropy analysis. RESULTS: A total of 159 sequences were successfully amplified from the gag genes of which 147 was CRF07_BC and 12 CRF08_BC. There were 3 main sub-clusters in CRF07_BC phylogenetic tree and they were named as sub-cluster IDU-Max (89 sequences), sub-cluster IDU-Min (22 sequences) and sub-cluster MSM (34 sequences) based on transmission.No international reference strain was closely related with these three sub-clusters except for one strain identified in Taiwan. All CRF07_BC recombinant strains were remarkable for their low interpatient diversity in gag genes (3.7%, 3.3% and 2.0% for isolates from IDU-Max, IDU-Min and MSM respectively).When compared with sub-cluster IDU-Max, there were 32 and 41 significantly different sites of nucleotide polymorphism compositions in sub-clusters IDU-Min and MSM. CONCLUSION: This is the first report of describing the existence of three main epidemic sub-clusters in CRF07_BC strains prevalent in Beijing. And IDU-Max sub-cluster is the dominant strain. The CRF07_BC in Beijing are less diverse than other strains and may be derived from a common ancestor.

Genetic Characteristics of Two Unique Recombinant Forms of HIV-1 CRF01_AE/CRF07_BC by Near Full-Length Genome from Men Who Have Sex with Men in Beijing, China.

Two HIV-1 infections with unassigned genotypes were identified during HIV-1 pretreatment drug resistance surveillance. The near full-length genome sequences of BL5040-00 and BL5085-00 were obtained and were classified as unique recombinant forms (URFs) between CRF01_AE and CRF07_BC. Simplot (version 3.5) analyses showed that the two URFs shared similar recombinant forms, and in the backbone belonging to CRF01_AE, the gag-pol, vpu, env, and nef gene fragments were genetically substituted by CRF07_BC. BL5040-00, with 10 breakpoints, had 6 CRF07_BC fragments and 5 CRF01_AE fragments, whereas BL5085-00, with 6 breakpoints, had 4 CRF07_BC fragments and 3 CRF01_AE fragments. BL5040-00 strain had two additional recombination breakpoints in pol-vif gene. The presence of URFs suggests that the men who have sex with men population in Beijing has an active HIV epidemic and the genetic diversity of HIV-1 is complex, emphasizing molecular epidemiology and disease progression monitoring should be strengthened.

Role of Proviral HIV-1 DNA Genotyping for People Living with HIV (PLWH) Who Had Low-Level Viremia While Receiving Antiretroviral Therapy.

Objective: To analyze the antiretroviral resistance in people living with HIV (PLWH) who developed low-level viremia (LLV) during antiretroviral therapy (ART) via sequencing of their HIV-1 proviral DNA and RNA and comparisons of their proviral DNA genotyping data with their past and synchronous RNA genotyping data. Patients and Methods: PLWH with LLV while receiving ART for 6 months or longer from January 2020 to September 2021 were included. HIV-1 proviral DNA and RNA were extracted from white-blood cells and concentrated plasma by ultracentrifugation, respectively, and HIV-1 pol gene fragments were amplified and sequenced. The concordance in the detection of resistance-associated mutations (RAMs) were examined between proviral DNA vs past RNA genotyping and proviral DNA vs synchronous RNA genotyping. Results: Of the 150 PLWH with LLV, 117 proviral DNA pol sequences detected in 105 PLWH were successfully amplified and RAMs were present in 27.6% and the rate of RAMs conferring low-level or greater resistance to antiretrovirals examined was 17.1%. Fifty-six and 57 PLWH had results of past and synchronous RNA genotyping, respectively, for comparisons with those of proviral DNA genotyping; and the concordance rates were 76.8% and 75.4%, respectively. However, proviral DNA genotyping lost than gained partial information on antiretroviral resistance compared with past or synchronous RNA genotyping. Conclusion: We found that the concordance between proviral DNA and past and synchronous RNA genotyping was moderate. Proviral DNA genotyping lost than gained more information on antiretroviral resistance compared with past or synchronous RNA genotyping. To optimize ART in PLWH with LLV, antiretroviral resistance profile should be interpreted in combination with proviral DNA and RNA genotyping and a comprehensive review of previous treatment history.

Humoral immune response following the inactivated quadrivalent influenza vaccination among HIV-infected and HIV-uninfected adults.

BACKGROUND: A limited amount of information is available about the immunogenicity of the quadrivalent inactivated influenza vaccine among human immunodeficiency virus (HIV)-infected individuals, especially in low and middle-income countries (LMICs). METHODS: HIV-infected adults and HIV-uninfected adults received a dose of quadrivalent inactivated influenza vaccine including strains of H1N1, H3N2, BV and BY. Enzyme-linked immunosorbent assay (ELISA) and hemagglutination-inhibition assay (HAI) were used to determine IgA, IgG antibody concentration and geometric mean titers (GMT) at day 0 and day 28, respectively. Associated factors contributing to seroconversion or GMT changes were analyzed using simple logistic regression model. RESULTS: A total of 131 HIV-infected and 55 HIV-uninfected subjects were included in the study. In both HIV-infected and uninfected arms, IgG and IgA against influenza A and B all increased significantly at day 28 after receiving QIV (P < 0.001). GMTs of post-vaccination at day 28 showed that HIV-infected persons with CD4 + T cell counts ≤ 350 cells/mm3 were statistically less immunogenic to all strains of QIV than HIV-uninfected ones (P < 0.05). HIV-infected participants with CD4 + T cell counts ≤ 350 cells/mm3 were less likely to achieve seroconversion to QIV (H1N1, BY and BV) than HIV-uninfected individuals at day 28 after vaccination (P < 0.05). Compared with HIV-infected patients with baseline CD4 + T cell counts ≤ 350 cells/mm3, individuals with baseline CD4 + T cell counts > 350 cell/mm3 seemed more likely to generate antibody responses to H1N1 (OR:2.65, 95 %CI: 1.07-6.56) and BY (OR: 3.43, 95 %CI: 1.37-8.63), and showed a higher probability of seroconversion to BY (OR: 3.59, 95 %CI: 1.03-12.48). Compared with nadir CD4 + T cell count ≤ 350 cell/mm3, individuals with nadir CD4 + T cell count > 350 cell/mm3 showed a higher probability of seroconversion to H1N1(OR: 3.15, 95 %CI: 1.14-8.73). CONCLUSION: Influenza vaccination of HIV-infected adults might be effective despite variable antibody responses. HIV-positive populations with CD4 + T cell counts ≤ 350 are less likely to achieve seroconversion. Further vaccination strategies could be developed for those with low CD4 T cell counts.

Drug Resistance to Integrase Strand-Transfer Inhibitors among HIV-1-Infected Adults in Guangdong, China.

BACKGROUND: Integrase strand-transfer inhibitor (INSTI)-containing regimens have gradually been administered in Guangdong Province, China beginning in 2016, and INSTI-related drug resistance (DR) may occur and should be monitored among HIV-1-infected patients. OBJECTIVE: To investigate the prevalence of INSTI-related resistance among HIV-1-infected individuals in Guangdong and provide evidence for the optimal administration of INSTIs. METHODS: This study recruited 1208 HIV-1-infected patients (including 404 ART-naive and 804 ART-experienced patients) between June 2021 and April 2022. The entire integrase gene was amplified from blood plasma. Demographic and epidemiological information were collected. INSTI mutations and susceptibility were interpreted using the Stanford HIV Drug Resistance Database HIVdb program. RESULTS: Of the 1208 enrolled individuals, 2.65% (32/1208) carried at least one INSTI major or accessory drug resistance mutation (DRM), with 1.49% (6/404) being from ART-naive individuals and 3.23% (26/804) from ART-experienced individuals. Among them, seven polymorphic major mutations were detected. Although no INSTI drug resistance was found among treatment-naive patients, seven ART-experienced patients (0.87%, 7/804) carried mutations conferring resistance to INSTIs. CONCLUSION: The overall prevalence of INSTI DRMs and DR was comparatively low among ART-naive and ART-treated populations in Guangdong; however, INSTI-related polymorphic mutations were observed. Surveillance should be reinforced before transfer to INSTI-containing regimens.

An open-label evaluation of safety and tolerability of coformulated bictegravir/emtricitabine/tenofovir alafenamide for post-exposure prophylaxis following potential exposure to human immunodeficiency virus-1.

BACKGROUND: Single-tablet regimen (STR) provides a convenient once-daily regimen for the prevention of human immunodeficiency virus (HIV) infection. Here, we investigated the safety and tolerability of coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a three-drug, STR for post-exposure prophylaxis (PEP) in Chinese individuals. METHODS: This was a prospective, open-label, single-arm trial conducted in a sexually transmitted diseases and acquired immunodeficiency syndrome clinic of a tertiary hospital in Beijing, China. Adults requiring PEP were prescribed BIC/FTC/TAF one pill once a day for 28 days. Clinical and laboratory data were collected and analyzed at baseline, weeks 2, 4, 8, 12, and 24. RESULTS: Of 112 participants enrolled in the study, 109 (97.3%) were male and the mean age was 30 ±â€Š8 years. PEP completion was 96.4% (95% confidence interval: 91.1-99.0%). Two participants stopped PEP after 2 days because the source partner was identified as HIV uninfected. One participant was excluded due to hepatitis B virus infection according to the exclusion criteria. One discontinued due to the participant's decision. No participant acquired HIV through week 24. Adherence was 98.9% (standard deviation [SD]: 3.3%) by self-reporting and 98.5% (SD: 3.5%) by pill count. Only five participants experienced mild clinical adverse events attributed to the study drug (including headache, diarrhea, and nausea) and four participants had elevated serum creatinine (grade 1). CONCLUSIONS: A once daily, STR of BIC/FTC/TAF used as PEP was safe and well-tolerated with a high rate of completion and adherence in Chinese. BIC/FTC/TAF may be a good option for PEP. TRIAL REGISTRATION: ChiCTR.org.cn, ChiCTR2100048080.

CRF07_BC is associated with slow HIV disease progression in Chinese patients.

HIV subtypes convey important epidemiological information and possibly influence the rate of disease progression. In this study, HIV disease progression in patients infected with CRF01_AE, CRF07_BC, and subtype B was compared in the largest HIV molecular epidemiology study ever done in China. A national data set of HIV pol sequences was assembled by pooling sequences from public databases and the Beijing HIV laboratory network. Logistic regression was used to assess factors associated with the risk of AIDS at diagnosis ([AIDSAD], defined as a CD4 count < 200 cells/µL) in patients with HIV subtype B, CRF01_AE, and CRF07_BC. Of the 20,663 sequences, 9,156 (44.3%) were CRF01_AE. CRF07_BC was responsible for 28.3% of infections, followed by B (13.9%). In multivariable analysis, the risk of AIDSAD differed significantly according to HIV subtype (OR for CRF07_BC vs. B: 0.46, 95% CI 0.39─0.53), age (OR for ≥ 65 years vs. < 18 years: 4.3 95% CI 1.81─11.8), and transmission risk groups (OR for men who have sex with men vs. heterosexuals: 0.67 95% CI 0.6─0.75). These findings suggest that HIV diversity in China is constantly evolving and gaining in complexity. CRF07_BC is less pathogenic than subtype B, while CRF01_AE is as pathogenic as B.

[Genotypic resistance mutations to antiretroviral drugs in newly confirmed human immunodeficiency virus infectors in Beijing].

OBJECTIVE: To examine the prevalence of drug resistance mutations among the treatment-naive HIV (human immunodeficiency virus) infectors living in Beijing so as to provide the basal information for clinical antiviral treatment. METHODS: HIV pol genes from plasma samples of 150 treatment-naive HIV-infected patients were amplified, sequenced and phylogenetically analyzed. And the drug-resistance associated mutations in protease and reverse transcriptase regions were analyzed with Stanford University HIV Drug Resistance Database. RESULTS: A total of 111 pol gene sequences were obtained. The overall prevalence of drug resistance was 8.1% (9/111), corresponding to 3.6% (4/111) for protease inhibitors, 1.8% (2/111) for nucleoside reverse transcriptase inhibitors and 3.6% (4/111) for non-nucleoside reverse transcriptase inhibitors. No drug resistance mutation was identified in 17 intravenous drug users. CONCLUSION: The prevalence of drug resistance is relatively high in the newly confirmed HIV infectors in Beijing. Regular surveillance and monitoring of drug-resistant HIV should be implemented.

Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family.

The 16p11.2 deletion is a recurrent genomic event and a significant risk factor for autism spectrum disorders (ASD). This genomic disorder also exhibits extensive phenotypic variability and diverse clinical phenotypes. The full extent of phenotypic heterogeneity associated with the 16p11.2 deletion disorder and the factors that modify the clinical phenotypes are currently unknown. Multiplex families with deletion offer unique opportunities for exploring the degree of heterogeneity and implicating modifiers. Here we reported the clinical and genomic characteristics of three 16p11.2 deletion carriers in a Chinese family. The father carries a de novo 16p11.2 deletion, and it was transmitted to the proband and sib. The proband presented with ASD, intellectual disability, learning difficulty, congenital malformations such as atrial septal defect, scoliosis. His dysmorphic features included myopia and strabismus, flat and broad nasal bridge, etc. While the father shared same neurodevelopmental problems as the proband, the younger brother did not show many of the proband's phenotypes. The possible unmasked mutation of TBX6 and MVP gene in this deleted region and the differential distribution of other genomic CNVs were explored to explain the phenotypic heterogeneity in these carriers. This report demonstrated the different developmental trajectory and discordant phenotypes among family members with the same 16p11.2 deletion, thus further illustrated the phenotypic complexity and heterogeneity of the 16p11.2 deletion.

Characteristics of Four Novel Recombinant Strains from the Backbone of CRF55_01B and CRF65_cpx in Beijing by Near Full-Length Genome.

The HIV-1 epidemic was mainly driven by men who have sex with men (MSM) recently in Beijing, China, with high genetic diversity. Novel recombinant strains were frequently reported at 3.4%-9.9%. It is imperative to interpret the recombinant modes and the putative transmission sources by near full-length genome (NFLG). Four individuals from the MSM population were identified as novel recombinant strains during surveillance of pretreatment drug resistance. NFLG sequences were harvested by near end-point dilution and nested PCR with two overlapping half fragments. Phylogenetic inference was performed with subtyping reference sequences and major parental strain sequences, to explore the patterns of genetic recombinant and potential sources of parent strains. The breakpoints were determined using SimPlot 3.5 to draw genome mosaic map, and the potential parental strains were confirmed by Mega 6.0 using segmental neighbor-joining trees. BL19487-00 and BL1948-00 sequences were obtained from epidemiologically linked individuals and shared similar breakpoints (HXB2 nt 4,497 ± 8 to 4,722) with substitution of subtype B pol gene segment in the backbone of CRF55_01B. BL3104-00 and BL4307-00 carried seven and eight breakpoints, respectively, in the backbone of CRF65_cpx with g5 CRF01_AE substitutions. The recombinant fragments were located around gag, pol, and env genes, with vpr-tat and nef-3'-LTR genes only for BL4307-00. No transmitted drug resistance was observed with the four unique recombinant forms (URFs), except for some drug resistance associated mutations. The advent of URFs around CRF55_01B and CRF65_cpx identified in recent years implied that the sexual behaviors were active and the epidemic of HIV was complicated among MSM in Beijing. Molecular epidemiological surveillance and precise control should be reinforced for this population.