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HIV drug resistance compromises the ability of anti-retroviral therapy (ART) to suppress viral replication, resulting in treatment failure. This study investigates the prevalence of pre-treatment drug resistance (PDR) in newly diagnosed individuals in a prosperous city (Wenzhou) in Southeastern China. A cross-sectional investigation was carried out among 473 newly diagnosed ART-naive HIV-1-infected individuals between January and December 2022. The protease-reverse transcriptase (PR-RT) region and integrase (IN) region of HIV-1 were amplified by two separately nested PCRs, followed by sequencing. Drug resistance mutations (DRMs) and drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) were analyzed. The PDR prevalence was 6.5% [95% CI: 4.4-9.1] for any anti-retroviral drug, 0.9% [95% CI: 0.3-2.3] for NRTIs, 4.1% [95% CI: 2.5-6.5] for NNRTIs, 1.8% [95% CI: 0.8-3.6] for PIs and 0.5% [95% CI: 0.1-1.8] for INSTIs. According to the subtyping results of the PR-RT region, 11 different subtypes and 31 unique recombinant forms (URFs) were found. CRF07_BC was the dominant subtype (53.7%, 233/434), followed by CRF01_AE (25.3%, 110/434). V179D (1.6%) and K103N (1.4%) were the most predominant types of NNRTI DRMs. Q58E (1.2%) and M184V (0.7%) were the most frequent PI DRMs and NRTI DRMs, respectively. The INSTI-related DRMs Y143S (causes high-level resistance to RAL) and G163K (causes low-level resistance to EVG and RAL) were found in one patient each. Given the relatively high PDR prevalence of NNRTI (4.1%), non-NNRTI-based ART may be preferred in the future. It is recommended to include genotypic resistance testing before starting ART in regions where feasible.
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Background: Long-term non-progressors (LTNPs) with HIV infection can naturally control viral replication for up to a decade without antiretroviral therapy (ART), but the underlying mechanisms of this phenomenon remain elusive. Methods: To investigate the relevant immune and inflammatory factors associated with this natural control mechanism, we collected plasma samples from 16 LTNPs, 14 untreated viral progressors (VPs), 17 successfully ART-treated patients (TPs), and 16 healthy controls (HCs). The OLINK immune response panel and inflammation panel were employed to detect critical proteins, and the plasma neutralizing activity against a global panel of pseudoviruses was assessed using TZM-bl cells. Results: The combination of IL17C, IL18, DDX58, and NF2 contributed to discriminating LTNPs and VPs. IL18 and CCL25 were positively associated with CD4+ T cell counts but negatively correlated with viral load. Furthermore, CXCL9 and CXCL10 emerged as potential supplementary diagnostic markers for assessing the efficacy of antiretroviral therapy (ART). Finally, TNFRSF9 displayed positive correlations with neutralization breadth and Geometry Median Titer (GMT) despite the lack of significant differences between LTNPs and VPs. Conclusion: In summary, this study identified a set of biomarkers in HIV-infected individuals at different disease stages. These markers constitute a potential network for immune balance regulation in HIV infection, which is related to the long-term control of HIV by LTNPs. It provides important clues for further exploring the immune regulatory mechanism of HIV.
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Biomarcadores , Infecciones por VIH , VIH-1 , Proteómica , Carga Viral , Humanos , Infecciones por VIH/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Infecciones por VIH/sangre , VIH-1/inmunología , Masculino , Adulto , Proteómica/métodos , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , China , Recuento de Linfocito CD4 , Sobrevivientes de VIH a Largo Plazo , Replicación Viral/efectos de los fármacos , Pueblos del Este de AsiaRESUMEN
With shared routes of transmission, HBV and HCV co-infection are estimated to occur more in subjects with HIV. This study aimed to characterize and describe the prevalence of HBV and HCV co-infections in a cohort of newly diagnosed HIV+ subjects living in China. We conducted a cross-sectional study among newly diagnosed HIV+ subjects aged 18-100 who participated in surveys on the national HIV molecular epidemiology in 2015 and 2023. (The epidemiological table survey is located in the national database alongside serologic testing). The chi-square test was used to identify changes in infections between the studying populations in 2015 and 2023, and conditional logistic regression models were fit to identify risk factors for each co-infection. Among the 11,024 newly diagnosed HIV+ subjects who were surveyed (n = 4501 in 2015; n = 6523 in 2023), the prevalence of HBV, HCV, and HBV/HCV in 2023 was lower than that in 2015, respectively. No decrease was observed in HCV co-infection in men who had sex with men (MSM) in North China, Northeast China, and East China. Increasing recognition among those at high risk of heterosexual transmission and those with low educational backgrounds is paramount to the prevention and control of HIV/HBV/HCV infections.
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The available knowledge regarding classification, nomenclature, and reference sequence selection for the various sub-subtypes of circulating recombinant forms (CRFs) is inadequate to fulfill the growing demands of research focused on HIV prevention. We analyzed the spread of CRF01_AE and CRF07_BC strains, mainly in China, to complement and update the existing nomenclature and to propose a reference sequence selection criteria for sub-subtypes of CRFs.
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Infecciones por VIH , Humanos , ChinaRESUMEN
OBJECTIVES: To evaluate the prevention efficacy of scaling up HIV/AIDS antiretroviral therapy (ART) on HIV transmission at the population level and determine associated factors of HIV secondary transmission. METHODS: We used HIV longitudinal molecular networks to assess the genetic linkage between baseline and newly diagnosed cases. A generalized estimating equation was applied to determine the associations between demographic, clinical characteristics and HIV transmission. RESULTS: Patients on ART had a 32% lower risk of HIV transmission than those not on ART. A 36% reduction in risk was also seen if ART-patients maintained their HIV viral load lower than 50 copies/mL. A 71% lower risk occurred when patients sustained ART for at least 3 years and kept HIV viral load less than 50 copies/mL. Patients who discontinued ART had a similar HIV transmission risk as those not on ART. Patients who were older, male, non-Han, not single, retired, infected via a heterosexual route of transmission and those who possessed higher CD4 counts had a higher risk of HIV transmission. HIV-1 subtype of CRF01_AE was less transmissible than other subtypes. CONCLUSIONS: The efficacy of ART in a real-world setting was supported by this longitudinal molecular network study. Promoting adherence to ART is crucial to reduce HIV transmission.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Humanos , Masculino , VIH-1/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Antirretrovirales/uso terapéutico , Recuento de Linfocito CD4 , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Carga Viral , Fármacos Anti-VIH/uso terapéuticoRESUMEN
BACKGROUND: Emerging HIV drug resistance caused by increased usage of antiretroviral drugs (ARV) could jeopardize the success of standardized HIV management protocols in resource-limited settings. OBJECTIVE: We aimed to characterize pretreatment HIV drug resistance (PDR) among HIV-positive individuals and risk factors in China in 2022. METHODS: This cross-sectional study was conducted using 2-stage systematic sampling according to the World Health Organization's surveillance guidelines in 8 provincial-level administrative divisions in 2022. Demographic information and plasma samples were obtained from study participants. PDR was analyzed using the Stanford HIV drug resistance database, and the Tamura-Nei 93 model in HIV-TRACE was used to calculate pairwise matches with a genetic distance of 0.01 substitutions per site. Logistic regression was used to identify and estimate factors associated with PDR. RESULTS: PDR testing was conducted on 2568 participants in 2022. Of the participants, 34.8% (n=893) were aged 30-49 years, 81.4% (n=2091) were male, and 3.2% (n=81) had prior ARV exposure. The prevalence of PDR to protease and reverse transcriptase regions, nonnucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 7.4% (n=190), 6.3% (n=163), 1.2% (n=32), and 0.2% (n=5), respectively. Yunnan, Jilin, and Zhejiang had much higher PDR incidence than did Sichuan. The prevalence of nonnucleoside reverse transcriptase inhibitor-related drug resistance was 6.1% (n=157) for efavirenz and 6.3% (n=163) for nevirapine. Multivariable logistic regression models indicated that participants who had prior ARV exposure (odds ratio [OR] 7.45, 95% CI 4.50-12.34) and the CRF55_01B HIV subtype (OR 2.61, 95% CI 1.41-4.83) were significantly associated with PDR. Among 618 (24.2%) sequences (nodes) associated with 253 molecular transmission clusters (size range 2-13), drug resistance mutation sites included K103, E138, V179, P225, V106, V108, L210, T215, P225, K238, and A98. CONCLUSIONS: The overall prevalence of PDR in China in 2022 was modest. Targeted genotypic PDR testing and medication compliance interventions must be urgently expanded to address PDR among newly diagnosed people living with HIV in China.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Humanos , Masculino , Femenino , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Estudios Transversales , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , VIH-1/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , China/epidemiología , Farmacorresistencia Viral/genéticaRESUMEN
OBJECTIVES: To assess the impact of pretreatment low-abundance HIV drug-resistant variants (LA-DRVs) on virological outcomes among ART-naive HIV-1-infected Chinese people who initiated ART. METHODS: A nested case-control study was conducted among HIV-1-infected individuals who had pretreatment drug resistance (PDR) genotypic results. Cases were defined as individuals with virological failure (HIV-1 RNA viral load ≥1000 copies/mL) after 1 year of ART, and controls were individuals from the same cohort whose viral load was less than 1000 copies/mL. Next-generation sequencing was used to identify low-abundance PDR mutations at detection thresholds of 10%, 2% and 1%. The mutant load was calculated by multiplying the abundance of HIV-1 drug-resistant variants by the pretreatment viral load. The impact of pretreatment low-abundance mutations on virological failure was estimated in logistic regression models. RESULTS: Participants (43 cases and 100 controls) were included in this study for the analysis. The proportion of participants with PDR was higher in cases than in controls at different detection thresholds (44.2% versus 22.0%, Pâ=â0.007 at 10% threshold; 58.1% versus 31.0%, Pâ=â0.002 at 2% threshold; 90.7% versus 69.0%, Pâ=â0.006 at 1% threshold). Compared with participants without PDR, participants with ≥10% detectable PDR mutations were associated with an increased risk of virological failure (adjusted OR 8.0, 95% CI 2.4-26.3, Pâ=â0.001). Besides this, individuals with pretreatment LA-DRVs (2%-9% abundance range) had 5-fold higher odds of virological failure (adjusted OR 5.0, 95% CI 1.3-19.6, Pâ=â0.021). Furthermore, LA-DRVs at 2%-9% abundance resistant to NRTIs and mutants with abundance of ≥10% resistant to NNRTIs had a 4-fold and 8-fold risk of experiencing virological failure, respectively. It was also found that a mutant load of more than 1000 copies/mL was predictive of virological failure (adjusted OR 7.2, 95% CI 2.5-21.1, Pâ=â0.0003). CONCLUSIONS: Low-abundance PDR mutations ranging from 2% to 9% of abundance can increase the risk of virological failure. Further studies are warranted to define a clinically relevant threshold of LA-DRVs and the role of NRTI LA-DRVs.
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Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , VIH-1/genética , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Estudios de Casos y Controles , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Seropositividad para VIH/tratamiento farmacológico , Carga Viral , VIH-2 , China/epidemiologíaRESUMEN
Background: High rates of disease progression and HIV drug resistance (HIVDR) among adults taking highly active antiretroviral treatment (HAART) in Sub-Saharan Africa were previously documented. However, children were generally not considered despite their greater risk. Hence, this study was aimed to evaluate HIV-1 disease progression and drug resistance mutation among children on first-line antiretroviral therapy in Ethiopia. Method: A longitudinal study was conducted among 551 HIV-positive children (<15 years old) recruited between 2017 and 2019 at 40 antiretroviral treatment delivery sites in Ethiopia. Disease progression was retrospectively measured over a 12-year (2007-2019) follow-up as the progress towards immunosuppression. Two consecutive viral load (VL) tests were conducted in 6-month intervals to assess virologic failure (VF). For children with VF, HIV-1 genotyping and sequencing was performed for the pol gene region using in-house assay validated at the Chinese Center for Disease Control and Prevention, and the Stanford HIVDB v9.0 algorithm was used for identification of drug resistance mutations. The Kaplan-Meier analysis and Cox proportional hazards regression model were used to estimate the rate and predictors of disease progression, respectively. Results: The disease progression rate was 6.3 per 100 person-years-observation (95% CI = 4.21-8.53). Overall immunosuppression (CD4 count < 200 cells/mm3) during the 12-year follow-up was 11.3% (95% CI = 7.5-15.1). Immunosuppression was significantly increased as of the mean duration of 10.5 (95% CI = 10.1-10.8) years (38.2%) to 67.8% at 12 years (p < 0.001). Overall, 14.5% had resistance to at least one drug, and 6.2% had multi-drug resistance. A resistance of 67.8% was observed among children with VF. Resistance to non-nucleotide reverse transcriptase inhibitors (NNRTI) and nucleotide reverse transcriptase inhibitors (NRTI) drugs were 11.4% and 10.1%, respectively. Mutations responsible for NRTI resistance were M184V (30.1%), K65R (12.1%), and D67N (5.6%). Moreover, NNRTI-associated mutations were K103N (14.8%), Y181C (11.8%), and G190A (7.7%). Children who had a history of opportunistic infection [AHR (95% CI) = 3.4 (1.8-6.2)], vitamin D < 20 ng/mL [AHR (95% CI) = 4.5 (2.1-9.9)], drug resistance [AHR (95% CI) = 2.2 (1.4-3.6)], and VF [AHR (95% CI) = 2.82 (1.21, 3.53)] had a higher hazard of disease progression; whereas, being orphan [AOR (95% CI) = 1.8 (1.2-3.1)], history of drug substitution [(AOR (95% CI) = 4.8 (2.1-6.5), hemoglobin < 12 mg/dL [AOR (95% CI) = 1.2 (1.1-2.1)] had higher odds of developing drug resistance. Conclusions: Immunosuppression was increasing over time and drug resistance was also substantially high. Enhancing routine monitoring of viral load and HIVDR and providing a vitamin-D supplement during clinical management could help improve the immunologic outcome. Limiting HAART substitution is also crucial for children taking HAART in Ethiopia.
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Introduction: The efficacy of treatment and clinical outcomes may be jeopardized by factors such as transmitted drug resistance (TDR) and the genetic diversity of the human immunodeficiency virus type 1 (HIV-1). This comprehensive study aims to examine the alterations in HIV-1 subtypes or sub-subtypes and TDR among Chinese individuals, who have been diagnosed with HIV infection and are previously untreated with antiretroviral therapy (ART), across the span of 2004 to 2022. Methods: Sequences of the HIV-1 pol gene region were obtained from ART-naïve HIV-positive individuals across 31 provincial-level administrative divisions between 2004 and 2022. To predict susceptibility to 12 antiretroviral drugs, the research utilized the Stanford HIV Drug Resistance Database. The Cochran-Armitage trend test facilitated the analysis of changes in HIV-1 subtype/sub-subtype prevalence and TDR. This analysis was conducted in alignment with the progression of the National Free Antiretroviral Treatment Program's stages between 2004 and 2022. Results: Among the 57,902 ART-naïve individuals infected with HIV, there was a notable decline in the prevalence of CRF01_AE, B, and C from 37.3%, 24.1%, and 1.3% respectively in 2004-2007 to 29.4%, 7.3%, and 0.2% respectively in 2020-2022. Simultaneously, a significant increase was observed in the proportions of CRF07_BC, CRF08_BC, CRF55_01B, other CRFs, and URFs, from 24.1%, 11.5%, 0.1%, 0.4%, and 0.9% respectively in 2004-2007 to 40.8%, 11.5%, 3.8%, 3.7%, and 2.8% respectively in 2020-2022 (all P<0.001 for trend). The prevalence of TDR to overall, non-nucleoside reverse transcriptase inhibitor (NNRTI), efavirenz, and nevirapine also significantly increased from 2.6%, 1.8%, 1.6%, and 1.8% respectively in 2004-2007 to 7.8%, 6.7%, 6.3%, and 6.7% respectively in 2020-2022 (all P<0.001 for trend). However, there were no meaningful changes in the TDR prevalence of nucleoside reverse transcriptase inhibitor and protease inhibitor. Notably, in 2020-2022, the overall TDR prevalence exceeded 15% in Xinjiang. Conclusions: The total prevalence of TDR in China has achieved a moderate level (7.8%) from 2020 to 2022, with NNRTI resistance standing prominently at 6.7%. Consequently, measures to curb TDR are urgently required, particularly among ART-naïve HIV-infected individuals in China.
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BACKGROUND: Hepatitis B virus (HBV) and syphilis have been the most common co-infections that hinder treatment outcomes and increase early mortality among people living with human immunodeficiency virus (PLHIV). In this study, we aimed to determine the burden of HBV and syphilis co-infections and its impact on treatment outcomes among PLHIV in Ethiopia. METHODS: We used data from the Ethiopian Population-based HIV Impact Assessment (EPHIA), which was a household-based national survey in 2017/2018. Human immunodeficiency virus (HIV) testing was done among 19,136 participants using the national testing algorithm and 662 participants (3.50%) were HIV positives who were further tested for viral hepatitis and syphilis co-infections using HBV surface antigen and Chembio DPP syphilis assay, respectively. Viral load, CD4 count and high-sensitivity C-reactive protein (hsCRP) were done to measure HIV treatment outcomes. Descriptive statistics were used to determine the burden of co-infections and a logistic regression model to evaluate the determinants of co-infections using STATA V17.0. RESULTS: Overall prevalence of HBV and syphilis co-infection was 5.5% and 2.2%, respectively. HBV and syphilis (double co-infection) was 5.9%. The highest prevalence of HBV co-infection was observed among 10-19 years age group (12.9%) and male participants (7.44%) while the highest syphilis co-infection was among people aged ≥50 years (3.5%) followed by age groups 40-49 (3.3%) and 10-19 years (3.2%). Syphilis co-infection was higher among males (5.2%) compared to females (1.1%). After adjusted regression analysis, HBV co-infected PLHIV had higher odds of virologic failure (AOR (95% confidence interval (CI)) = 6.3 (4.2-14.3)), immunosuppression (CD4 count < 500 cells/mm3) (AOR (95%CI) = 2.1(1.3-4.9)) and inflammation (hsCRP >10 mg/dL) (AOR (95%CI) = 9.2(4.3-14.6)). Immunosuppression was also significantly higher among syphilis co-infected PLHIV (AOR (95%CI) = 3.4 (1.3-5.2)). CONCLUSIONS: Burden of HBV and syphilis co-infections is high particularly among male and adolescent PLHIV and these co-infections hinder virologic and immunologic outcome in Ethiopia. Hence, the program shall enhance HBV and syphilis testing and treatment.
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Coinfección , Infecciones por VIH , Hepatitis B , Sífilis , Femenino , Adolescente , Masculino , Humanos , Niño , Adulto Joven , Adulto , Virus de la Hepatitis B , Sífilis/tratamiento farmacológico , Sífilis/epidemiología , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Coinfección/epidemiología , Etiopía/epidemiología , Proteína C-Reactiva , Hepatitis B/complicaciones , Hepatitis B/tratamiento farmacológico , Hepatitis B/epidemiología , Resultado del Tratamiento , PrevalenciaRESUMEN
INTRODUCTION: A lower adherence rate (percentage of individuals taking drugs as prescribed) to ART may increase the risk of emergence and transmission of HIV drug resistance, decrease treatment efficacy, and increase mortality rate. Exploring the impact of ART adherence on the transmission of drug resistance could provide insights in controlling the HIV epidemic. METHODS: We proposed a dynamic transmission model incorporating the CD4 cell count-dependent rates of diagnosis, treatment and adherence with transmitted drug resistance (TDR) and acquired drug resistance. This model was calibrated and validated by 2008-2018 HIV/AIDS surveillance data and prevalence of TDR among newly diagnosed treatment-naive individuals from Guangxi, China, respectively. We aimed to identify the impact of adherence on drug resistance and deaths during expanding ART. RESULTS: In the base case (ART at 90% adherence and 79% coverage), we projected the cumulative total new infections, new drug-resistant infections, and HIV-related deaths between 2022 and 2050 would be 420â539, 34â751 and 321â671. Increasing coverage to 95% would reduce the above total new infections (deaths) by 18.85% (15.75%). Reducing adherence to below 57.08% (40.84%) would offset these benefits of increasing coverage to 95% in reducing infections (deaths). Every 10% decrease in adherence would need 5.07% (3.62%) increase in coverage to avoid an increase in infections (deaths). Increasing coverage to 95% with 90% (80%) adherence would increase the above drug-resistant infections by 11.66% (32.98%). CONCLUSIONS: A decrease in adherence might offset the benefits of ART expansion and exacerbate the transmission of drug resistance. Ensuring treated patients' adherence might be as important as expanding ART to untreated individuals.
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Síndrome de Inmunodeficiencia Adquirida , Fármacos Anti-VIH , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , China/epidemiología , Resistencia a Medicamentos , Cumplimiento y Adherencia al Tratamiento , Farmacorresistencia Viral , Prevalencia , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacologíaRESUMEN
BACKGROUND: Attrition due to loss to follow-up or termination of antiretroviral therapy (ART) among HIV-infected patients in care may increase the risk of emergence and transmission of drug resistance (TDR), diminish benefit of treatment, and increase morbidity and mortality. Understanding the impact of attrition on the epidemic is essential to provide interventions for improving retention in care. METHODS: We developed a comprehensive HIV transmission dynamics model by considering CD4 + cell count dependent diagnosis, treatment, and attrition involving TDR and acquired drug resistance. The model was calibrated by 11 groups HIV/AIDS surveillance data during 2008-2018 from Guangxi, China, and validated by the prevalence of TDR among diagnosed treatment-naive individuals. We aimed to investigate how attrition would affect the transmission of HIV and drug-resistance when expanding ART. RESULTS: In the base case with CD4 + cell count dependent per capita attrition rates 0.025â¼0.15 and treatment rates 0.23â¼0.42, we projected cumulative total new infections, new drug-resistant infections, and HIV-related deaths over 2022-2030 would be 145â391, 7637, and 51â965, respectively. Increasing treatment rates by 0.1â¼0.2 can decrease the above total new infections (deaths) by 1.63â¼2.93% (3.52â¼6.16%). However, even 0.0114â¼0.0220 (0.0352â¼0.0695) increase in attrition rates would offset this benefit of decreasing infections (deaths). Increasing treatment rates (attrition rates) by 0.05â¼0.1 would increase the above drug-resistant infections by 0.16â¼0.30% (22.18â¼41.15%). CONCLUSION: A minor increase in attrition can offset the benefit of treatment expansion and increase the transmission of HIV drug resistance. Reducing attrition rates for patients already in treatment may be as important as expanding treatment for untreated patients.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Farmacorresistencia Viral , China/epidemiología , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Fármacos Anti-VIH/uso terapéuticoRESUMEN
HIV-1 infection is mediated by a viral envelope subsequently binding to CD4 receptor and two main coreceptors, CCR5 (R5) for primary infection and CXCR4 (X4) in chronic infection. Switching from R5 to X4 tropism in HIV-1 infection is associated with increased viral pathogenesis and disease progression. The coreceptor switching is mainly due to variations in the V3 loop, while the mechanism needs to be further elucidated. We systematically studied the determinant for HIV-1 coreceptor switching by substitution of the genes from one R5 and one X4 pseudoviruses. The study results in successfully constructing two panels of chimeric viruses of R5 to X4 forward and X4 to R5 reverse switching. The determinants for tropism switching are the combined substitution of the V3 loop and C4 region of the HIV-1 envelope. The possible mechanism of the tropism switching includes two components, the V3 loop to enable the viral envelope binding to the newly switched coreceptor and the C4 region, to compensate for the loss of fitness caused by deleterious V3 loop mutations to maintain the overall viral viability. The combined C4 and V3 substitution showed at least an eightfold increase in replication activity compared with the pseudovirus with only V3 loop substitution. The site-directed mutations of N425R and S440-I442 with charged amino acids could especially increase viral activity. This study could facilitate HIV-1 phenotype surveillance and select right entry inhibitor, CCR5 or CXCR4 antagonists, for antiviral therapy.
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Infecciones por VIH , VIH-1 , Humanos , VIH-1/genética , Secuencia de Aminoácidos , Receptores CCR5/genética , Receptores CCR5/metabolismo , Receptores del VIH/genética , Receptores del VIH/metabolismo , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Mutación , Proteína gp120 de Envoltorio del VIH/genética , Proteína gp120 de Envoltorio del VIH/metabolismoRESUMEN
BACKGROUND: Treatment as prevention evolved into the universal HIV test-and-treat (UTT) strategy, which entails testing to the general population and treatment to every people living with HIV. We investigated universal testing (UT) performance and its determinants in urban Ethiopia and explore magnitude of late diagnosis and its impact on disease stages. METHOD: We used data from the Ethiopia Population Based HIV Impact assessment (EPHIA), conducted in 2017/2018 which was a cross-sectional and household-based study. For current analysis, we considered self-report first diagnosis to estimate universal testing irrespective of their serostatus and also consider HIV LAg avidity vs viral load vs plasma antiretroviral drug level algorithm to categorize the late diagnosis. We finally evaluate disease stages using CD4 count and viral load. A 2-level multilevel mixed-effect logistic regression model was employed. The effects of individual-level predictors were quantified by the estimates from the fixed-effect part of the model with p-value < 0.05. RESULT: Data were collected from 18,926 adults among those 29.4% of people living in Urban Ethiopia were never tested for HIV. Never tested females was 26.4% (95% CI = 25.3; 27.5). Never tested among divorced and widowed were 19.4% (95% CI: 17.3; 21.8) and 28.3% (95% CI: 24.6; 32.2), respectively. Never tested among elderly and youth were high (28.3% among 45-54 years old) to (41.2% among 55-64 years old) to 47.8% among 15-24 years old. Overall, late HIV diagnosis among adults in urban Ethiopia was 25.9% (95% CI: 21.7, 30.2). Late diagnosis varies by region ranged from 38.1% in the Gambella to 5.8% in Benishangul Gumuz. Advanced immune suppression (CD4 count < 350 cells/µl) among newly diagnosed long-term infection were significantly higher compared to those who were recently infected which accounted 47.8% (95%CI = 33.2-52.1) and 30.9% (95%CI = 21.3-32.2), respectively. Moreover, Viral load suppression were significantly lower among those who were late diagnosed 26.1% (95%CI = 13.6-33.8) compared to those of newly infected 89.6% (95%CI = 76.2; 93.4). CONCLUSION: With the aim of UT for high risk and priority population, the low rate of HIV testing among widowed, elderly, young adolescent and women in urban Ethiopia calls for enhanced HIV testing. Moreover, the low HIV testing and high late diagnosis among the high-burden regions calls for region-specific intervention. Advanced disease stages as a result of the high proportion of late diagnosis may impact on fueling community transmission and hinder treatment outcome among PLHIV.
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Background: Studies have shown high early mortality after initiation of highly active antiretroviral therapy (HAART). We examined change in three-year survival and predictors of mortality of patients initiating HAART in Ethiopia since 2007 to 2019. Methods: A retrospective cohort study was conducted in 47 health facilities (HFs) using records of 11,013 adult patients initiating HAART from 2007 to 2019. Study subjects were stratified as four different cohorts based on their calendar year of HAART initiation: 2007-2010, 2011-2013, 2014-2016, and 2017-2019. HFs were selected using probability proportional to size of patients. Survival rate and predictors of mortality were estimated by the calendar year using the Kaplan-Meier and Cox proportional hazard, respectively. We generated a pooled estimate of survival rate and predicators of mortality. Results: Data from 1881, 3868, 3004, and 2260 patients were retrieved from each of the cohorts. Overall mortality for all cohorts at all times was 10.3%. A gradual decline of mortality was observed in the first three years of follow-up since 2007-2016 which were 21.37%, 10.03%, and 4.34% among patients who initiated HAART in 2007, 2011, and 2014 respectively. A mortality jump of 9.25% was observed among patents initiating HAART in 2017, which coincided with political instability happened in the country. Of the 21,638 person-years of follow-up among 11,013 adults, mortality was 5.23/100 person-years, while disaggregated by the cohorts, it was 14.77, 5.06, 2.12, and 4.17 per 100 person-years, respectively. Among all the cohorts, patients with CD4 count of ≤200 cells/mm3, unsuppressed viral load, poor adherence, and drug resistance in all cohorts, respectively, have overall 2.0 (95%CI = 1.35 - 2.69), 4.66 (95%CI = 2.53 - 6.72), 6.78 (95%CI = 3.4 - 10.3), and 10.02 (95%CI = 6.91 - 13.82) times of mortality risk than those without. Patients with bedridden for cohort initiating HAART during 2007 and 2011 were 2.0 (95%CI = 1.35 - 2.69) times of mortality risk than those without. Conclusion: Patients initiating HAART from 2007 to 2016 have continuously improved their survival during three-year cohort follow-up in Ethiopia. The significant decline of survival among those who initiate HAART as of 2017 calls for program intervention. Low CD4 counts, unsuppressed viral load, poor adherence, and drug resistance could be used as predictors for increased mortality to monitor the quality of HAART and improve clinical management of HIV/AIDS patients.
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Terapia Antirretroviral Altamente Activa , Adulto , Humanos , Etiopía/epidemiología , Estudios Retrospectivos , Recuento de Linfocito CD4 , Carga ViralRESUMEN
Background: This study is used to analyze the genetic network of HIV sexual transmission in rural areas of Southwest China after expanding antiretroviral therapy (ART) and to investigate the factors associated with HIV sexual transmission through the genetic network. Materials and methods: This was a longitudinal genetic network study in Guangxi, China. The baseline survey and follow-up study were conducted among patients with HIV in 2015, and among those newly diagnosed from 2016 to 2018, respectively. A generalized estimating equation model was employed to explore the factors associated with HIV transmission through the genetic linkage between newly diagnosed patients with HIV (2016-2018) and those at baseline (2015-2017), respectively. Results: Of 3,259 identified HIV patient sequences, 2,714 patients were at baseline, and 545 were newly diagnosed patients with HIV at follow-up. A total of 8,691 baseline objectives were observed by repeated measurement analysis. The prevention efficacy in HIV transmission for treated HIV patients was 33% [adjusted odds ratio (AOR): 0.67, 95% confidence interval (CI): 0.48-0.93]. Stratified analyses indicated the prevention efficacy in HIV transmission for treated HIV patients with a viral load (VL) of <50 copies/ml and those treated for 4 years with a VL of <50 copies/ml to be 41 [AOR: 0.59, 95% CI: 0.43-0.82] and 65% [AOR: 0.35, 95% CI: 0.24-0.50], respectively. No significant reduction in HIV transmission occurred among treated HIV patients with VL missing or treated HIV patients on dropout. Some factors were associated with HIV transmission, including over 50 years old, men, Zhuang and other nationalities, with less than secondary schooling, working as a farmer, and heterosexual transmission. Conclusion: This study reveals the role of ART in reducing HIV transmission, and those older male farmers with less than secondary schooling are at high risk of HIV infection at a population level. Improvements to ART efficacy for patients with HIV and precision intervention on high-risk individuals during the expansion of ART are urgently required.
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Objectives: We investigated the prevalence of pretreatment drug resistance (PDR), the molecular transmission network among HIV-positive individuals, and the impact of virological failure on those who received antiretroviral therapy (ART) in China. Methods: Based on the World Health Organization (WHO) surveillance guidelines for PDR, a baseline survey and follow-up were conducted in 2018 and 2021, respectively. Demographic information and plasma samples were obtained from all participants. HIV pol gene region sequences were used to analyze the PDR and molecular transmission networks using the Stanford HIV database algorithm and HIV-TRACE, respectively. This study assessed the odds ratios (OR) of PDR to virological failure (viral load ≥ 50 copies/mL) after 3 years of ART using multivariable logistic regression. Results: Of the 4,084 individuals, 370 (9.1%) had PDR. The prevalence of PDR to non-nucleoside reverse transcriptase inhibitors (5.2%) was notably higher than that to nucleoside reverse transcriptase inhibitors (0.7%, p < 0.001), protease inhibitors (3.0%, p < 0.001), and multidrug resistance (0.3%, p < 0.001). A total of 1,339 (32.8%) individuals from 361 clusters were enrolled in the molecular transmission network. Of the 361 clusters, 22 included two or more individuals with PDR. The prevalence of virological failure among HIV-positive individuals after 3 years of ART without PDR, those with PDR to Chinese listed drugs, and those with PDR to other drugs was 7.9, 14.3, and 12.6%, respectively. Compared with that in HIV-positive individuals without PDR, virological failure after 3 years of ART was significantly higher (OR: 2.02, 95% confidence interval (CI): 1.25-3.27) and not significantly different (OR: 1.72, 95% CI: 0.87-3.43) in individuals with PDR to Chinese listed drugs and those with PDR to other drugs, respectively. Missed doses in the past month were significantly associated with virological failure (OR, 2.82; 95% CI: 4.08-5.89). Conclusion: The overall prevalence of PDR was close to a high level and had an impact on virological failure after 3 years of ART. Moreover, HIV drug-resistant strains were transmitted in the molecular transmission network. These results illustrate the importance of monitoring PDR and ensuring virological suppression through drug adherence.
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To study the characteristics of HIV pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in Hefei, a cross-sectional survey was used to collect 816 samples from newly reported HIV infections from 2017 to 2020 and 127 samples from HIV infections with virological failure from 2018 to 2019 in Hefei. HIV drug resistance levels and drug resistance mutations were interpreted using the Stanford Drug Resistance Database. Molecular networks were constructed by HIV-TRACE. Among the newly reported infections in Hefei, the prevalence of PDR was 6.4% (52/816). The drug resistance mutations were mainly V179E/D/T (12.4%), K103N (1.3%), and V106I/M (1.3%). In addition, it was found that the CRF55_01B subtype had a higher drug resistance rate than other subtypes (p < 0.05). Molecular network analysis found that K103N and V179E may be transmitted in the cluster of the CRF55_01B subtype. The prevalence of ADR among HIV infections with virological failure was 38.6% (49/127), and the drug resistance mutations were mainly M184V (24.4%), K103N/S (15.7%), Y181C (11.0%), G190S/A/E (10.2%), and V106M/I (10.2%). The molecular network was constructed by combining HIV infections with virological failure and newly reported infections; M184V and Y181C may be transmitted between them. The chi-square trend test results indicated that the higher the viral load level, the greater the number of newly reported infections linked to the infections with virological failure in the molecular network. In conclusion, interventions should focus on infections of the CRF55_01B subtype to reduce the transmission of drug-resistant strains. However, improving the treatment effect of HIV infections is beneficial for reducing the second-generation transmission of HIV.
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OBJECTIVES: The aim of this study was to evaluate HIV-1 drug resistance among patients failing first-line antiretroviral therapy in Ethiopia. METHODS: A total of 699 adults infected with HIV (aged ≥15 years) who failed first-line Antiretroviral Therapy (ART) were recruited between 2017 and 2019 from 63 ART-providing sites in Ethiopia. Treatment failure was defined as patients with two consecutive viral loads (VLs) ≥1000 copies/mL within six months of follow-up. The pol gene region of HIV-1 was amplified and sequenced using an in-house assay of the Chinese Center for Disease Prevention and Control. The Stanford HIVDB v9.0 algorithm was used for identification of resistance mutations. Resistance mutations were characterized according to the 2019 International AIDS Society-USA mutation list. P values of <0.05 were considered statistically significant during multivariate analysis, which was done using SPSS v26.0 (SPSS Inc., Chicago, IL). RESULTS: Overall, HIV drug resistance (HIVDR) among patients failing first-line therapy in Ethiopia was 77.8%. Non-nucleoside/tide reverse transcriptase inhibitors (NNRTI) and NRTI resistance were 75.7% and 71.2%, respectively. Neverapine (NVP) and Efavirenz (EFV) accounted for 74.2% and 60.8% of HIVDR, respectively. About half (48.1%) of NRTI-associated mutations were responsible for Abacavir resistance, while 34% were responsible for multi-NRTI resistance. Mutations responsible for resistance to the commonly used EFV and NVP accounted for 62.9%, while resistance to Etravirine, Doravirine, and Rilivirine, which were not part of the country's ART program, were 37.1%, and can be explained by cross-resistance within the drug class. Protease Inhebitor(PI)associated resistance was detected in only 1.6% of the study's participants. The most common mutations identified were M184V (30.1%), K103N (18.7%), Y181C (13.6%), and K65R (12.1%). In a multivariate logistic regression analysis, predictors of HIVDR were prior ART exposure (adjusted odds ratio [AOR] = 2.3; 95% confidence interval [CI] = 1.8, 3.6), absence of HIV status disclosure (AOR=2.05; 95%CI=1.26, 3.35), CD4 count of ≤200 cells/mm3 (AOR=1.94; 95%CI=1.21, 3.12), and bedridden status (AOR = 4.16; 95% CI = 3.21, 5.16). CONCLUSION: The high-levels of HIVDR among patients with failure of first-line ART in Ethiopia calls for individualized HIVDR testing. Mutations associated with multi-NRTI and NNRTI cross-resistance may alert the program for considering drugs of higher genetic barrier targeting protease and other regions. Patients with low CD4 count and those who are bedridden should be given special attention for the potential development of HIVDR during clinical management.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Adulto , Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral/genética , Etiopía , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Humanos , Inhibidores de la Transcriptasa InversaRESUMEN
What is already known about this topic?: While antiretroviral therapy (ART) has been rapidly scaled-up among the population living with human immunodeficiency virus or acquired immune deficiency syndrome (HIV/AIDS) patients since 2016, pretreatment drug resistance (PDR) has also increased. What is added by this report?: PDR has an impact on ART outcomes. After one year of ART, the risk of virological failure in individuals with PDR was found to be 2.3 times higher than that of individuals without PDR. Moreover, patients with PDR to non-nucleoside reverse transcriptase inhibitors (NNRTIs) had an even higher risk of virological failure, with an odds ratio of 2.8 as compared with those without PDR. What are the implications for public health practice?: PDR is associated with an increased risk of virological failure. It is recommended to regularly implement PDR monitoring in order to provide information to optimize ART regimens and to prevent HIV drug resistance.