The effect of pretreatment HIV-1 drug resistance on the response to first-line combination antiretroviral therapy (ART) in sub-Saharan Africa has not been assessed. We studied pretreatment drug resistance and virological, immunological, and drug-resistance treatment outcomes in a large prospective cohort.HIV-1 infected patients in the PharmAccess African Studies to Evaluate Resistance Monitoring (PASER-M) cohort started non-nucleoside reverse transcriptase inhibitor-based ART at 13 clinical sites in six countries, from 2007 to 2009. We used the International Antiviral Society-USA drug resistance mutation list and the Stanford algorithm to classify participants into three pretreatment drug resistance categories: no pretreatment drug resistance, pretreatment drug resistance with fully active ART prescribed, or pretreatment drug resistance with reduced susceptibility to at least one prescribed drug. We assessed risk factors of virological failure (≥400 copies per mL) and acquired drug resistance after 12 months of ART by use of multilevel logistic regression with multiple imputations for missing data. CD4 cell count increase was estimated with linear mixed models.Pretreatment drug resistance results were available for 2579 (94%) of 2733 participants; 2404 (93%) had no pretreatment drug resistance, 123 (5%) had pretreatment drug resistance to at least one prescribed drug, and 52 (2%) had pretreatment drug resistance and received fully active ART. Compared with participants without pretreatment drug resistance, the odds ratio (OR) for virological failure (OR 2·13, 95% CI 1·44-3·14; p<0·0001) and acquired drug-resistance (2·30, 1·55-3·40; p<0·0001) was increased in participants with pretreatment drug resistance to at least one prescribed drug, but not in those with pretreatment drug resistance and fully active ART. CD4 count increased less in participants with pretreatment drug resistance than in those without (35 cells per μL difference after 12 months; 95% CI 13-58; p=0·002).At least three fully active antiretroviral drugs are needed to ensure an optimum response to first-line regimens and to prevent acquisition of drug resistance. Improved access to alternative combinations of antiretroviral drugs in sub-Saharan Africa is warranted.The Netherlands Ministry of Foreign Affairs.Copyright © 2012 Elsevier Ltd. All rights reserved.

A molecular epidemiology study was conducted among more than 100 human immunodeficiency virus type 1 (HIV-1) subtype C seropositive intravenous drug users (IDUs) from China. Genotyping based on the envelope C2V3 coding region revealed the highest homology of the most prevalent virus strains circulating throughout China to subtype C sequences of Indian origin. Based on these results, a virtually full-length genome representing the most prevalent class of clade C strains circulating throughout China was directly amplified from peripheral blood mononuclear cells of a selected HIV-infected IDU and subcloned. Sequence analysis identified a mosaic structure, suggesting extensive intersubtype recombination events between genomes of the prevalent clade C and (B')-subtype Thai virus strains of that geographic region. Recombinant Identification Program analysis and phylogenetic bootstrapping suggested that there were 10 breakpoints (i) in the gag-pol coding region, (ii) in vpr and at the 3' end of the vpu gene, and (iii) in the nef open reading frame. (B')-sequences therefore include (i) several insertions in the gag-pol coding region; (ii) 3'-vpr, the complete vpu gene, and the first exons of tat and rev; and (iii) the 5' half of the nef gene. Breakpoints located in the vpr/vpu coding region as well as in the nef gene of 97cn54 were found at almost identical positions of all subtype C strains isolated from IDUs living in different areas of China, suggesting a common ancestor for the C/B' recombinant strains. More than 50% of well-defined subtype B-derived cytotoxic T-lymphocyte epitopes within Gag and Pol and 10% of the known epitopes in Env were found to exactly match sequences within in this clade C/B' chimeric reference strain. These results may substantially facilitate a biological comparison of clade C-derived reference strains as well as the generation of useful reagents supporting vaccine-related efforts in China.

To determine the origin and evolutionary history of two predominant and closely-related circulating recombinant forms (CRF07_BC and CRF08_BC), recombinant structures and phylogenies of 7 unique recombinant forms comprised of subtypes of B' (Thai B linage) and C (designated URFs_BC) from archival specimens of injection drug users (IDUs) collected in 1996 to 1998 from western Yunnan and 4 circulating recombinant forms with B'/C recombinants recently identified (designated nCRFs_BC) in China were compared with those of CRF07_BC and CRF08_BC. The results showed that 5 of 7 URFs_BC and all the nCRFs_BC shared recombination breakpoints with CRF07_BC and/or CRF08_BC. Yunnan URFs_BC consistently occupied the basal branch positions compared with CRF07_BC, CRF08_ BC, and nCRFs_BC in phylogenetic trees. The estimated most recent common ancestors (tMRCA) for Yunnan URFs_BC were from -1987, approximately half a decade earlier than those for CRF07_BC (-1994) and CRF08_BC (-1992). Discrete phylogeographic and spatial diffusion analysis revealed that both CRF07_BC and CRF08 BC came from western Yunnan in the early 1990s. Our results provide compelling evidence for western Yunnan as the geographic origin of CRF07_BC and CRF08_BC, which emerged from a swarm of URFs_BC by a series of recombination events in western Yunnan in the early 1990s.

The prevalence of CRF07_BC is 39.7% and has become the most infectious HIV strain in China. To study the transmission and diffusion trajectory of CRF07_BC in China and to prevent further expansion of its transmission. A total of 16,635 sequences of the CRF07_BC pol gene were collected from 1997-2020. We characterized the gene subtypes according to a phylogenetic tree analysis. A 0.50% molecular network was constructed to analyze the transmission relationship among different provinces for CRF07_BC and its two epidemic clusters. Spatial and temporal propagation characteristics were analyzed according to phylogeographic analysis. Finally, we evaluated the differences in transmission of CRF07_BC-O, and CRF07_BC-N. Our dataset included 8,816 sequences of CRF07_BC-N and 7,819 sequences of CRF07_BC-O. There were 7,132 CRF07_BC sequences in the molecular network, and the rate of clustered was 42.9%. Compared to CRF07_BC-O, CRF07_BC-N showed significantly (P&lt;0.001) higher transmission-specific rates. CRF07_BC originated among injecting drug users (IDUs), and spread to men who have sex with men (MSMs) and heterosexual individuals (HETs), while MSMs also transmitted directly to HETs. CRF07_BC-O and CRF07_BC-N were prevalent in Xinjiang and Sichuan, respectively, before spreading interprovincially. In modern China, CRF07_BC-N occurs in five of the major economic zones. The CRF07_BC strain, which has contributed to the highest number of HIV infections in China, is divided into two epidemic clusters. Compared with CRF07_BC-O, risk of transmission is much greater in CRF07_BC-N, which is predominantly prevalent in economically developed provinces, and both MSMs and IDUs have transmitted this epidemic cluster to HETs. High-resolution, large-scale monitoring is a useful tool in assessing the trend and spread of the HIV epidemic. The rapidly developing economy of China requires an equally rapid response to the prevention and control of infectious diseases.

The increasing prevalence of HIV drug resistance poses a significant challenge. This study aimed to investigate the epidemiological dynamics and molecular characteristics of pretreatment drug resistance (PDR) and acquired drug resistance in Shaoxing, Eastern China. Methods: From 2022 to 2024, 571 newly diagnosed HIV-infected individuals and 119 individuals with antiretroviral treatment failure were enrolled. Molecular transmission networks and Bayesian analysis were employed to identify key drug-resistant clusters and trace their origins. Results: The overall PDR prevalence was 14.4% (85/571). PDR to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 9.8% (56/571), significantly higher than to NRTIs (1.1%, 6/571) and PIs (3.7%, 21/571) (χ2 = 50.014, p < 0.001). Molecular network analysis identified large clusters harboring K103N and Q58E resistance mutations within the CRF07_BC subtype. Bayesian analysis estimated their introduction into Shaoxing from Guangdong Province around 2016 and 2017, respectively. Integrated network analysis revealed close linkages between virological failure and newly diagnosed cases, highlighting the role of treatment failure in resistance transmission. Conclusion: Targeted interventions against specific subtypes and transmission clusters, alongside continuous resistance surveillance, are essential to curb the spread of drug-resistant HIV and optimize ART regimens.

目的 了解河北省接受抗逆转录病毒治疗（ART）HIV/AIDS患者的HIV-1基因亚型、耐药特征及其耐药影响因素，为HIV/AIDS患者实施精准治疗提供指导。方法 收集2023年1—12月在河北省接受6个月以上ART的HIV/AIDS患者血浆样本进行病毒载量（VL）检测，对VL≥50 copies/mL的样本进行HIV-1 pol基因扩增，判定亚型并进行耐药分析，非条件Logistic回归进行耐药影响因素分析。结果 扩增成功的612例患者中，HIV-1毒株以CRF01_AE、CRF07_BC为主，B、CRF08_BC、CRF65_cpx、URFs等多亚型并存。总耐药率为37.75%（231/612），其中病毒学抑制失败（VF）患者耐药率为44.59%（165/370），低病毒血症（LLV）患者耐药率为27.27%（66/242）。抗病毒治疗药物中NNRTIs（35.13%）、NRTIs（23.37%）耐药率明显高于PIs耐药率（1.80%），且NNRTIs-NRTIs双重耐药情况较为频繁。Logistic回归分析发现耐药发生风险与CD4⁺T淋巴细胞计数、基因亚型以及VL有关，CD4⁺T淋巴细胞计数水平越低耐药发生风险越高，CRF07_BC相较于CRF01_AE耐药风险低（aOR=0.384，95%CI：0.248~0.593），VF耐药风险高于LLV。结论 河北省接受ART的HIV/AIDS患者耐药风险较高，对接受ART的HIV/AIDS患者应进行及时的病毒载量及耐药监测，为实施精准治疗提供指导。

The most common antiretroviral treatment (ART) received by individuals infected with HIV-1 in China is the combination therapy, comprised of nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). To assess the prevalence of HIV-1 drug resistance and subtypes in Honghe of Yunnan, China, patient plasmas from ART-failed individuals were collected from January 2010 to December 2012. Genotyping was conducted using an in-house assay on patient plasmas. A total of 254 pol sequences were obtained. The prevalence of drug resistance was 47.2% in ART-failed individuals. Of these drug-resistant individuals, 51.7% harbored HIV strains dually resistant to NRTIs and NNRTIs or protease inhibitors (PIs) (34.2% for NNRTIs and 14.2% for NRTIs). Mutations such as M184V, A62V, T69Ins, K103N, Y181C, and G190A were common among the ART-failed individuals. The frequencies of M184V, A62V, and K103N were 20.5%, 11.0%, and 23.6%, respectively. The most common subtypes in Honghe were CRF08_BC (68.50%) and CRF07_BC (12.20%). The subtypes were almost consistent in different time points for one individual. When receiving ART for 6-12 months, the frequency of HIV-1 drug-resistant variants ranked first. This study shows that the high prevalence of HIV drug resistance observed among the ART-failed individuals should be of increasing concern (monitoring of resistance mutations) in ART regions and facilitate developing novel strategies for prevention and control of HIV infection in China.