National Free Antiretroviral Treatment Program Research Articles

Factors associated with immunological non-response after ART initiation: a retrospective observational cohort study

BackgroundAmong people living with HIV (PLHIV) on antiretroviral therapy (ART), the mortality of immunological non-responders (INRs) is higher than that of immunological responders (IRs). However, factors associated with immunological non-response following ART are not well documented.MethodsWe obtained data for HIV patients from the National Free Antiretroviral Treatment Program database in China. Patients were grouped into IRs (CD4 cell count ≥ 350 cells/μl after 24 months’ treatment), immunological incomplete responders (ICRs) (200–350 cells/μl) and INRs (< 200 cells/μl). Multivariable logistic regression was used to assess factors associated with immunological non-response.ResultsA total of 3900 PLHIV were included, among whom 2309 (59.2%) were IRs, 1206 (30.9%) ICRs and 385 (9.9%) INRs. In multivariable analysis, immunological non-response was associated with being male (2.07, 1.39–3.09), older age [40–49 years (vs. 18–29 years): 2.05, 1.29–3.25; 50–59 years: 4.04, 2.33-7.00; ≥ 60 years: 5.51, 2.84–10.67], HBV co-infection (1.63, 1.14–2.34), HCV co-infection (2.01, 1.01–4.02), lower CD4 + T cell count [50–200 cells/μl (vs. 200–350 cells/μl): 40.20, 16.83–96.01; < 50 cells/μl: 215.67, 85.62-543.26] and lower CD4/CD8 ratio (2.93, 1.98–4.34) at baseline. Compared with patients treated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens, those receiving protease inhibitors (PIs) based regimens were less likely to be INRs (0.47, 0.26–0.82).ConclusionsWe found a sizable immunological non-response rate among HIV-infected patients. Being male, older age, coinfection with HBV and HCV, lower CD4 + T cell count and lower CD4/CD8 ratio are risk factors of immunological non-response, whereas PIs-based regimens is a protective factor.

Incidence of low-level viremia and its impact on virologic failure among people living with HIV who started an integrase strand transfer inhibitors: a longitudinal cohort study

BackgroundLow-level viremia (LLV) has been identified as a potential precursor to virologic failure (VF), yet its clinical implications, particularly within the context of Integrase Strand Transfer Inhibitors (INSTIs)-based regimens, remain insufficiently explored. The study aimed to investigate the relationship between LLV and VF within ART-naïve patients on INSTIs-based regimens in China.MethodsA longitudinal cohort study was conducted with ART-naïve patients aged ≥ 18 years at Beijing Ditan Hospital, under the Chinese National Free Antiretroviral Treatment Program (NFATP). The LLV was defined as a viral load (VL) ranging from 50 to 199 copies/mL after six months of ART initiation, and VF as a VL ≥ 200 copies/mL. Sensitive analyses were also performed, defining LLV as 50–999 copies/mL and VF as exceeding 1000 copies/mL. Multivariate logistic regression, Kaplan-Meier (KM) curve, and Generalized Estimating Equation (GEE) models were used to evaluate the risk factors associated with LLV and VF events.ResultsThe study involved 830 ART-naïve patients, comprising 600 in the INSTIs group and 230 in the protease inhibitors (PIs) group. LLV events were observed in 10.4% of patients on PIs-based regimens and and 3.2% on INSTIs-based regimens (P < 0.001). INSTIs-based regimens demonstrated a protective effect against LLV events (aHR = 0.27, 95% CI 0.137–0.532). VF events occurred in 10.9% of patients on PIs-based regimens and 2.0% on INSTIs-based regimens, respectively (P < 0.001). The occurrence of LLV events significantly increased the risk of VF by 123.5% (95% CI 7.5%-364.4%), while the integrase inhibitors were associated with a 76.9% (95% CI 59.1%-86.9%) reduction in VF risk.ConclusionOur findings indicate that INSTIs-based regimens are critical protective factors against LLV and subsequent VF. These results underscore the importance of HIV viral load monitoring to ensuring effective treatment outcomes, highlighting the necessity for prompt and precise monitoring to refine HIV treatment methodologies.

Cost-effectiveness analysis of antiretroviral drugs for treatment-naive HIV infection in China

IntroductionDolutegravir (DTG)-based regimen was included in the expanded formulary of China's National Free Antiretroviral Treatment Program at the end of 2021. Yet high price of DTG and lack of health economic evaluation in China present barriers for implementation of the regimen. The study aims to investigate the lifetime cost-effectiveness of DTG-based regimen for treatment-naive HIV infection in China.MethodsA decision-analytic Markov model was used to obtain the costs and effectiveness of four regimens: Arm A, efavirenz (EFV)-based regimen; Arm B, DTG-based regimen; Arm C, elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine (EVG/c/FTC/TAF) regimen; Arm D, abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) regimen. The potential impact of national centralized drug procurement policy was assessed in scenario analysis. The results were further validated through sensitivity analysis.ResultsCompared with other three regimens, DTG-based regimen led to the fewest cumulative adverse reactions, opportunistic infections and deaths. Compared with EFV-based regimen, the base-case ICERs for DTG-based regimen were 13,357 (USD/QALY) and 13,424 (USD/QALY) from the healthcare system and societal perspective respectively. In the policy scenario analysis with the procurement price of DTG equal to that of LPV/r, DTG-based regimen would be dominant. The model results remained robust in sensitivity analyses.ConclusionsDTG-based regimen for treatment-naive patients is likely to be cost-effective and deserve wider implementation in China. This study strongly suggests the centralized procurement of DTG to minimize cost and maximize cost-effectiveness.

Increasing trends of overweight and obesity in treatment-naive people living with HIV in Shenzhen from 2014 to 2020: an emerging health concern.

With the early initiation of antiretroviral therapy (ART) in China, the demographics of treatment-naïve people living with HIV (PLWH) are moving closer to those of the general population, which is characterized by a gradual increase in metabolic indicators. However, the epidemic trends of overweight and obesity over the past decade in treatment-naïve PLWH ready to initiate ART have not yet been investigated. A cross-sectional study was conducted, including 12,135 consecutive treatment-naïve PLWH ready to initiate ART in Shenzhen, using data retrieved from the China National Free Antiretroviral Treatment Program database from 2014 to 2020. The chi-square test was used to examine the trends of overweight and obesity between age groups, and multivariate logistic regression was used to identify the association of overweight and obesity with hyperglycemia and dyslipidemia. During the 7-year study period, 12,135 treatment-naïve PLWH ready to initiate ART were included, among whom 1,837 (15.1%) were overweight and 388 (3.2%) were obese. The prevalence of overweight rose from 11.4 to 17.3% (Z = -4.58, P for trend <0.01) and that of obesity from 2.0% to 4.2% (Z = -6.45, P for trend <0.01) from 2014 to 2020. The annual prevalence of overweight was the highest in the age group of participants >35 years compared to prevalence in other age groups during the period 2014-2020. Compared with those who were not overweight or obese, PLWH who were overweight or obese were more likely to have hyperglycemia (aOR 1.84, 95% CI: 1.37-2.49 for overweight; aOR 2.68, 95% CI: 1.62-4.44 for obesity), higher ALT level (aOR 2.70, 95% CI: 2.33-3.13 for overweight; aOR 3.85, 95% CI: 2.93-5.05 for obesity), higher TG levels (aOR 1.89, 95% CI 1.63-2.19 for overweight; aOR 2.56, 95% CI 1.97-3.32 for obesity), and lower HDL levels (aOR 1.67, 95% CI 1.44-1.95 for overweight; aOR 2.06, 95% CI 1.54-2.77 for obesity). The prevalence of overweight and obesity in treatment-naive PLWH increased steadily from 2014 to 2020 in Shenzhen. Overweight and obese in treatment-naive PLWH ready to initiate ART were associated with dyslipidemia and hyperglycemia. Public health authorities should take proactive steps to address these issues by implementing targeted screening, intervention programs including lifestyle modifications, and integrated healthcare services.

Changes in HIV-1 Subtypes/Sub-Subtypes, and Transmitted Drug Resistance Among ART-Naïve HIV-Infected Individuals - China, 2004-2022.

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. 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. 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. 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.

Treatment Outcomes of HIV Infected Children After Initiation of Antiretroviral Therapy in Southwest China: An Observational Cohort Study.

BackgroundThe number of HIV infected children receiving antiviral treatment in Guangxi is increasing. Understanding factors and trends of mortality and attrition in HIV-infected children under antiretroviral therapy (ART) was an urgent need to improve treatment outcomes. This study aimed to estimate mortality and attrition rates and identify factors that were associated with mortality and attrition after ART initiation among children with HIV in Guangxi, China between 2004 and 2018.MethodsCohort study data were extracted from the National Free Antiretroviral Treatment Program (NFATP) database, which has standard guidelines for core treatment indicators and other data at all HIV/AIDS treatment facilities in Guangxi. A total of 901 HIV-infected children who have started ART were included in the study. The study collected the following data: age, gender, WHO clinic stages before ART, CD4 cell count before ART, Cotrimoxazole prophylaxis (CTX) use before ART, initial ART regimen, malnutrition before ART, abnormal liver function before ART, abnormal kidney function before ART, severe anemia before ART, and the time lag between an HIV diagnosis and ART initiation.ResultsHIV-infected children under ART had a mortality rate of 0.87 per 100 person-years [95% Confidence Interval (CI) 0.63–1.11], and an attrition rate of 3.02 per 100 person-years (95% CI 2.57–3.47). Mortality was lower among children with a CD4 count between 200 and 500 copies/ml [Adjusted Hazard Ratio (AHR) 0.22, 95% CI 0.09–0.55], and CD4 count ≥500 copies/ml (AHR 0.10, 95% CI 0.03–0.29); but higher among children with late ART initiation at 1–3 months (AHR 2.30, 95% CI 1.07–4.94), and at ≥3 months (AHR 2.22, 95% CI 1.04–4.74). Attrition was lower among children with a CD4 count ≥500 copies/ml (AHR 0.62, 95% CI 0.41–0.95), but higher among children with late ART initiation at 1–3 months (AHR 1.55, 95% CI 1.05–2.30).ConclusionSupportive programs are needed to educate children's families and parents on early ART, link HIV-infected children to care and retain them in care among other programs that treat and manage the medical conditions of HIV-infected children before ART initiation.

Determinants of suboptimal immune recovery among a Chinese Yi ethnicity population with sustained HIV suppression

ObjectivesDespite sustained viral suppression with effective antiretroviral therapy (ART), HIV-infected patients with suboptimal immune recovery are still at high risk of both non-AIDS-related and AIDS-related events. The aim of this study was to investigate determinants potentially associated with suboptimal CD4 + T cell count recovery during free ART with sustained viral suppression among an HIV-infected Yi ethnicity population in Liangshan Prefecture, an area in China with high HIV prevalence.MethodsThis retrospective study included HIV-infected Yi adults (≥ 18 years and baseline CD4 + T cell count less than 500 cells/μL) for whom ART supported by National Free Antiretroviral Treatment Program was initiated between January 2015 and December 2018 in Zhaojue County, Liangshan Prefecture. Virological suppression (viral load < 50 copies/mL) was achieved within 12 months after ART initiation, and sustained virological suppression was maintained. Multivariate log-binomial regression analysis was used to assess determinants of suboptimal immune recovery.ResultsThere were 140 female and 137 male patients in this study, with a mean age of 36.57 ± 7.63 years. Most of the Yi patients were infected through IDU (48.7%) or heterosexual contact (49.8%), and the anti-HCV antibody prevalence was high (43.7%, 121/277). Of the 277 patients with a mean ART duration of 3.77 ± 1.21 years, complete immune recovery occurred in only 32.9%. The baseline CD4 + T cell count in patients with suboptimal and intermediate immune recovery was 248.64 ± 108.10 and 288.59 ± 108.86 cells/μL, respectively, which was much lower than the baseline 320.02 ± 123.65 cells/μL in patients who achieved complete immune recovery (p < 0.001). Multivariable analysis demonstrated that low pre-ART CD4 + cell count and coinfection with HCV were associated with immune recovery of the HIV patients.ConclusionsOur study suggests that for HIV-infected Yi patients in Liangshan Prefecture, prompt ART initiation after diagnosis of HIV infection should be applied, and curative HCV treatment should be given to patients with HCV/HIV coinfection to improve the immunological effectiveness of ART.Trial registration None

Treatment outcomes of HIV patients with hepatitis B and C virus co-infections in Southwest China: an observational cohort study

BackgroundAntiretroviral therapy (ART) has reduced mortality among people living with HIV (PLWH) in China, but co-infections of hepatitis B virus (HBV) and hepatitis C virus (HCV) may individually or jointly reduce the effect of ART. This study aimed to evaluate the impacts of HBV/HCV coinfections on treatment drop-out and mortality among PLWH on ART.MethodsA retrospective cohort study analysis of 58 239 people living with HIV (PLWH) who initiated antiretroviral therapy (ART) during 2010–2018 was conducted in Guangxi Province, China. Data were from the observational database of the National Free Antiretroviral Treatment Program. Cox proportional hazard models were fitted to evaluate the effects of baseline infection of HBV or HCV or both on death and treatment attrition among PLWH.ResultsOur study showed high prevalence of HBV (11.5%), HCV (6.6%) and HBV-HCV (1.5%) co-infections. The overall mortality rate and treatment attrition rate was 2.95 [95% confidence interval (CI) 2.88–3.02] and 5.92 (95% CI 5.82–6.01) per 100 person-years, respectively. Compared with HIV-only patients, HBV-co-infected patients had 42% higher mortality [adjusted hazard ratio (aHR) = 1.42; 95% CI 1.32–1.54], HCV-co-infected patients had 65% higher mortality (aHR = 1.65; 95% CI 1.47–1.86), and patients with both HCV and HBV co-infections had 123% higher mortality (aHR = 2.23; 95% CI 1.87–2.66).ConclusionsHBV and HCV coinfection may have an additive effect on increasing the risk of all-cause death among PLWH who are on ART. It is suggested that there is need for primary prevention and access to effective hepatitis treatment for PLWH.Graphical

Epidemiological trends of severely immunosuppressed people living with HIV at time of starting antiretroviral treatment in China during 2005–2018

ObjectivesHigh HIV-related mortality is mainly associated with severe immunosuppression (CD4 count < 50 cells/μL) in people living with HIV (PLWH). This study intended to explore the trends in epidemic and early mortality among PLWH with severe immunosuppression for further targeted intervention. MethodsWe extracted the data of treatment-naïve PLWH with severe immunosuppression from China's National Free Antiretroviral Treatment (ART) Program database. Early mortality (within 6 or 12 months after initiating ART) and spatial, temporal, and population distribution were analyzed during 2005–2018. ResultsOf 748,066 treatment-naïve PLWH, 105,785 (14.1%) were severely immunosuppressed PLWH aged more than 15-year-old. The proportion of severely immunosuppressed PLWH peaked at 31.4% and then decreased with time, leveling off at approximately 11–12% from 2015 onward. Early mortality rates of these PLWH declined significantly (from 17.0% to 8.1% after 6 months of initiating ART; 20.4% to 10.6% after 12 months; both p values < 0.01) from 2005–2007 to 2016–2018. In the South-central and Southwest, the number of these PLWH was larger than that in the other regions during 2005–2018, and it increased to 4780 (37.1%) and 3370 (26.2%) in 2018. The proportion of PLWH aged 30–44 years among all treatment-naïve severely immunosuppressed PLWH in each region was higher than that of other age groups during 2005–2018. After the proportion decreased during 2005–2007, the proportion of PLWH aged 45–59 years in Southwest and South-central were increased steadily from 11% (69/626) and 16.7% (358/2140) in 2007 to 33.8% (1138/3370) and 34.0% (1626/4780) in 2018, respectively; the proportion of PLWH aged ≥60 years showed an increasing trend during 2005–2018; while changes in the proportion of those age groups were less pronounced in North and Northeast. The proportion of PLWH infected by heterosexual contact was high at 83% (2798/3370) in Southwest, and 75.1% (3588/4780) in South-central in 2018; conversely, proportion of PLWH infected by homosexual contacts was largest in North (57.8% [500/865]) and Northeast (59.9% [561/936]). ConclusionsThe persistent burden of treatment-naïve PLWH with severe immunosuppression remains challenging. Our results provide evidence for policy-makers to allocate resources and establish targeting strategies to identify early infection of PLWH.

Development and external validation of a prognostic model for survival of people living with HIV/AIDS initiating antiretroviral therapy.

Background: Most existing prognostic models for people living with HIV/AIDS (PLWHA) were derived from cohorts in high-income settings established a decade ago and may not be applicable for contemporary patients, especially for patients in developing settings. The aim of this study was to develop and externally validate a prognostic model for survival in PLWHA initiating ART based on a large population-based cohort in China.Methods: We obtained data for patients from the Chinese National Free Antiretroviral Treatment Program database. The derivation cohort consisted of PLWHA treated between February 2004 and December 2019 in a tertiary center in Guangzhou, South China, and validation cohort of patients treated between February 2004 to December 2018 in another tertiary hospital in Shenyang, Northeast China. We included ART-naive patients aged above 16 who initiated a combination ART regimen containing at least three drugs and had at least one follow-up record. We assessed 20 candidate predictors including patient characteristics, disease characteristics, and laboratory tests for an endpoint of death from all causes. The prognostic model was developed from a multivariable cox regression model with predictors selected using the least absolute shrinkage and selection operator (Lasso). To assess the model's predictive ability, we quantified the discriminative power using the concordance (C) statistic and calibration accuracy by comparing predicted survival probabilities with observed survival probabilities estimated with the Kaplan–Meier method.Findings: The derivation cohort included 16481 patients with a median follow-up of 3·41 years, among whom 735 died. The external validation cohort comprised 5751 participants with a median follow-up of 2·71 years, of whom 185 died. The final model included 10 predictors: age, body mass index, route of HIV acquisition, coinfection with tuberculosis, coinfection with hepatitis C virus, haemoglobin, CD4 cell count, platelet count, aspartate transaminase, and plasma glucose. The C-statistic was 0·84 (95% confidence interval 0·82–0·85) in internal validation after adjustment of optimism and 0·84 (0·82–0·87) in external validation, which remained consistently above 0·75 in all landmark time points within five years of follow up when using time-updated laboratory measurements. The calibration accuracy was satisfactory in both derivation and validation cohorts.Interpretation: We have developed and externally validated a model to predict long-term survival in PLWHA on ART. This model could be applied to individualized patient counseling and management during treatment, and future innovative trial design.Funding: Natural Science Foundation of China Excellent Young Scientists Fund, Natural Science Foundation of China International/Regional Research Collaboration Project, Natural Science Foundation of China Young Scientist Fund, the National Science and Technology Major Project of China,National Special Research Program of China for Important Infectious Diseases, 13th Five-Year Key Special Project of Ministry of Science and Technology, and the Joint-innovation Program in Healthcare for Special Scientific Research Projects of Guangzhou.

Critical appraisal and external validation of a prognostic model for survival of people living with HIV/AIDS who underwent antiretroviral therapy

BackgroundHIV/AIDS remains a leading cause of death worldwide. Recently, a model has been developed in Wenzhou, China, to predict the survival of people living with HIV/AIDS (PLWHA) who underwent antiretroviral therapy (ART). We aimed to evaluate the methodological quality and validate the model in an external population-based cohort.MethodsPrediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess the risk of bias of the Wenzhou model. Data were from the National Free Antiretroviral Treatment Program database. We included PLWHA treated between February 2004 and December 2019 in a tertiary hospital in Guangzhou city, China. The endpoint was all-cause deaths and assessed until January 2020. We assessed the discrimination performance of the model by Harrell’s overall C-statistics and time-dependent C-statistics and calibration by comparing observed survival probabilities estimated with the Kaplan–Meier method versus predicted survival probabilities. To assess the potential prediction value of age and gender which were precluded in developing the Wenzhou model, we compared the discriminative ability of the original model with an extended model added with age and gender.ResultsBased on PROBAST, the Wenzhou model was rated as high risk of bias in three out of the four domains (selection of participants, definition of outcome, and methods for statistical analysis) mainly because of the misuse of nested case–control design and propensity score matching. In the external validation analysis, 16758 patients were included, among whom 743 patients died (mortality rate 11.41 per 1000 person-years) during follow-up (median 3.41 years, interquartile range 1.64–5.62). The predictor of HIV viral load was missing in 14361 patients (85.7%). The discriminative ability of the Wenzhou model decreased in the external dataset, with the Harrell’s overall C-statistics being 0.76, and time-dependent C-statistics dropping from 0.81 at 6 months to 0.48 at 10 years after ART initiation. The model consistently underestimated the survival, and the level was 6.23%, 10.02%, and 14.82% at 1, 2, and 3 years after ART initiation, respectively. The overall and time-dependent discriminative ability of the model improved after adding age and gender to the original model.ConclusionThe Wenzhou prognostic model is at high risk of bias in model development, with inadequate model performance in external validation. Thereby, we could not confirm the validity and extended utility of the Wenzhou model. Future prediction model development and validation studies need to comply with the methodological standards and guidelines specifically developed for prediction models.

Sex differences in HIV treatment outcomes and adherence by exposure groups among adults in Guangdong, China: A retrospective observational cohort study

IntroductionWe aimed to assess sex differences in treatment outcomes and adherence comparing men who have sex with women (MSW), men who have sex with men (MSM), and women who have sex with men (WSM), as well as men and women who inject drugs living with HIV on combination antiretroviral therapy (ART) in Guangdong, China. MethodsWe performed a retrospective observational cohort study with data from the National Free Antiretroviral Treatment Program database. We included ART-naive patients aged 18 to 80 years who had contracted HIV through sex or injecting drugs, initiated first-line ART between January 2004 and December 2016, and had at least 60 days of follow-up. Participants were followed for five years. Kaplan-Meier analysis and Cox proportional hazard models were used to evaluate all-cause mortality. Cumulative incidence function and Cox proportional hazards models accounting for competing risks were used to evaluate disease progression to AIDS. Modified Poisson regression models were used to evaluate immunological and virological responses and loss to follow-up. Repeated measures analysis was used to evaluate regular CD4+ cell count, HIV viral load monitoring, ART adherence, side effects, and interruption of ART. FindingsWe included 26,409 persons living with HIV. 21,779 (82·5%) people acquired HIV through sex (5118 WSM [23·5%], 8506 MSW [39·0%], 8175 MSM [37·5%]), and 4610 people (17·5%) through injection drug use (249 women [5·4%], 4361 men [94·6%]). Among those infected through sex, MSW had increased risks of all-cause mortality (adjusted hazard ratio [aHR] 1·48, 95% CI 1·20–1·83), progression to AIDS (1·27, 1·09–1·47), virological failure (adjusted incidence rates ratio [aIRR] 1·27, 95% CI 1·09–1·48), and loss to follow-up (1·22, 1·10–1·35) compared to WSM. In contrast, MSM had lower risk of all-cause mortality (aHR 0·49, 95%CI 0·32–0·76), disease progression to AIDS (0·83, 0·68–1·00), and virological failure (aIRR 0·78, 95%CI 0·65–0·94), were more likely to receive regular CD4+ cell count (1·08, 1·07–1·10) and HIV viral load monitoring (1·13, 1·12–1·15), were less likely to report missing ART doses (0·54, 0·49–0·61), interrupt ART (0·34, 0·26–0·44), or be lost to follow-up (0·56, 0·49–0·65) compared to WSM. Men who inject drugs were almost twice as likely as women who inject drugs to die (aHR 1·72, 95%CI 1·03–2·85), experience disease progression to AIDS (2·05, 1·18–3·57), virological failure (aIRR 1·81, 95%CI 1·19–2·76), report ART side effects (1·78, 1·43–2·22), and interruptions in ART (2·29, 1·50–3·50). InterpretationOur findings highlight the importance of identifying potentially at-risk MSW and promoting HIV education and testing among them. Particular attention is warranted among men who inject drugs to improve timely HIV diagnosis, drug interaction management, and retention in treatment. Additional research from rural settings is needed to assess the long-term treatment outcomes and adherence in MSM with HIV.

90-90-90 cascade analysis on reported CLHIV infected by mother-to-child transmission in Guangxi, China: a modeling study

The prevalence of HIV in Guangxi was very high, and there were many children living with HIV (CLHIV) because of larger baseline of pregnant women infected by HIV. It is necessary for children to explore the status of antiretroviral therapy (ART) on different initial CD4 counts in children with HIV infected by mother-to-child transmission (MTCT) in Guangxi and to evaluate the progress towards the 90-90-90 targets proposed by UNAIDS/WHO. Based on a retrospective observational cohort of children with HIV infected from the Guangxi Center for Disease Prevention and Control (CDC), the variables of all patients included viral loads, CD4 counts, laboratory results and WHO clinical staging of HIV/AIDS were collected. Several indicators were defined before analyzed: (1) diagnosis of MTCT: infants born to HIV-positive mothers who tested positive for HIV twice before 18 months; (2) ART initiation: the children who were enrolled in the treatment cohort and were still having HIV monitoring as of 6 months before date censored and (3) viral suppression: a recently viral load measurement that was less than 1000 copies per milliliter. The number of CLHIV in Guangxi was projected by using the estimates of the national HIV/AIDS prevalence from China CDC. An Autoregressive Integrated Moving Average (ARIMA) model and the Holt Exponential Smoothing (ES) model were used to predict the number of CLHIV, the diagnosed CLHIV, the diagnosed CLHIV receiving ART and the number of them achieving viral suppression, in 2019 and 2021, respectively. In this 14-year HIV/AIDS treatment cohort, 807 children who were HIV infected by MTCT were enrolled. The ARIMA and Holt ES models showed that by the end of 2019, 82.71% of all CLHIV in Guangxi knew their HIV status, 84.50% of those diagnosed had initiated ART, and 85.68% of those on ART had durable viral suppression. By the end of 2021, 93.51% of all CLHIV in Guangxi will know their HIV status, 84.28% of those diagnosed will have initiated antiretroviral therapy, and 85.83% of those on ART will have durable viral suppression. Therefore, in 2021, Guangxi fails to achieve the WHO/UNAIDS 90-90-90 targets for CLHIV, and there is still a wide time interval between the first HIV-positive diagnosis and ART initiation. National free antiretroviral treatment program (NFATP) requires strong enforcement to reduce the prevalence of later chronic diseases and complications.

Efficacy and Tolerability of Lopinavir/Ritonavir- and Efavirenz-Based Initial Antiretroviral Therapy in HIV-1-Infected Patients in a Tertiary Care Hospital in Beijing, China.

Background: Lopinavir/ritonavir (LPV/r) is a major antiretroviral treatment in China, but little is known about the performance of first-line LPV/r-based regimen in treatment-naïve patients with human immunodeficiency virus type 1 (HIV-1) infection. This study aims to assess the efficacy and adverse effect events of LPV/r plus lamivudine and tenofovir or zidovudine as an initial antiretroviral treatment in HIV-1-infected individuals for whom cannot take efavirenz (EFV) or is allergic to EFV.Methods: We performed a retrospective study of patients registering with the China’s National Free Antiretroviral Treatment Program from July 2012 to January 2017, followed at a tertiary care hospital in Beijing, China. The primary outcome was the proportion of subjects with HIV-1 RNA ≤40 copies/ml at 6 and 24 months of treatment. We assessed the immunological response and adverse events.Results: In total, 4,862 patients were enrolled in the study and 237 were eligible for analysis in each study arm. During the first six months, virological suppression was better with the LPV/r-based regimen than with the EFV-based regimen (93.80 vs 87.80% for P < 0.05). Viral suppression rates continued to increase until 12 months, remain steady thereafter until 24 months, for both groups. The multilevel analysis revealed that patients in the LPV/r group were more likely to display improvements in CD4 T-cell count over time than those in the EFV group (P < 0.001). Grade 3 or 4 laboratory adverse events were observed in 14 patients (5.91%) from the LPV/r group and three patients (1.20%) in EFV group.Conclusion: Our findings demonstrate that LPV/r-containing regimens are effective and well-tolerated in Chinese treatment-naïve patients with HIV-1 infection.

Simultaneous quantitation of zidovudine, efavirenz, lopinavir and ritonavir in human hair by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry

Nowadays, zidovudine, efavirenz, lopinavir and ritonavir are important components of the second-line antiretroviral therapeutic regimen of National Free Antiretroviral Treatment Program in China. The measurement of antiretroviral drugs in hair will facilitate for the evaluation of the long-term adherence to highly active antiretroviral therapy. Nevertheless, no study illustrated simultaneous quantitation of the four drugs in hair. The study intended to develop a simple, sensitive and selective method for simultaneous quantitation of the four drugs in hair. The detection employed high liquid chromatography tandem mass spectrometry with atmospheric pressure chemical ionization in positive mode. Hair samples were incubated in methanol at 40 °C for 16 h. The method showed the limit of detection at 18, 8, 5 and 6 pg/mg for zidovudine, efavirenz, lopinavir and ritonavir, respectively. The linear range (R2 > 0.99) was 36–5000 pg/mg for zidovudine, 16–5000 pg/mg for efavirenz, 10–50,000 pg/mg for lopinavir and 12–12,500 pg/mg for ritonavir. The intra-day and inter-day coefficients of variation were <15% and the recovery varied from 88.1 to 110.5%. The population analysis revealed that patients with high adherence showed significantly higher drug concentrations in hair than those with low adherence for both AZT and EFV (ps < 0.05). There was high association in drug contents in hair between AZT and EFV or LPV and RTV (ps < 0.05).

Gender Differences in Outcomes of Antiretroviral Treatment Among HIV-Infected Patients in China: A Retrospective Cohort Study, 2010-2015.

Women now account for about half of all people living with HIV worldwide, but researchers lack clear information and large population-based study about gender differences in treatment outcomes. A nationwide retrospective observational cohort study with data from the China National Free Antiretroviral Treatment Program was performed. Antiretroviral-naive patients older than 18 years initiating standard antiretroviral therapy between January 1, 2010, and December 31, 2011, were included and followed up to December 31, 2015. We used modified Poisson regression models to estimate the impact of gender on virological suppression and retention in treatment, and Kaplan-Meier analysis and Cox proportional hazard models to evaluate gender difference in mortality. Sixty-eight thousand six hundred forty-six patients [46,083 (67.1%) men and 22,563 (32.9%) women] with HIV met eligibility criteria. Women were significantly more likely to achieve virological suppression than men both at 12 months [adjusted relative risk (aRR) 1.02, 95% confidence interval (CI): 1.01 to 1.03, P < 0.001] and 48 months (aRR 1.01, 95% CI: 1.00 to 1.02, P = 0.005) after initiating antiretroviral treatment. Women were also more likely to remain in treatment at 12 months (aRR 1.02, 95% CI: 1.01 to 1.02, P < 0.001) and 48 months (aRR 1.04, 95% CI: 1.03 to 1.05, P < 0.001), although the difference became insignificant in alive patients. All-cause mortality was lower in women than in men (2.34 vs. 4.03 deaths/100PY, adjusted hazard ratio 0.72, 95% CI: 0.67 to 0.77, P < 0.001). In China, women are more likely to achieve virological suppression, remain in treatment, and have a significantly lower risk of death than men. Future studies could take both biological and sociobehavioral factors into analysis to clarify the influence factors.

Immunologic treatment failure among HIV-infected adult patients in Jiangsu province, China

The National Free Antiretroviral Treatment Program was implemented in Jiangsu Province, China in 2005. We conducted a retrospective, open cohort study to determine treatment failure rates and associated risk factors. Data were obtained from the national web-based antiretroviral treatment database. WHO criteria were used to define immunologic treatment failure. Kaplan-Meier methods were used to determine treatment failure rates and Cox proportional hazards modeling was used to identify risk factors. A total of 5,083 (87.8%) having at least one CD4 cell count measure were included from 2005 to 2013. Overall, 30.4% had immunologic treatment failure with cumulative treatment failure rates increasing to 50.5% at month 60 and 64.1% at month 90. Factors predicting treatment failure included being treated in the Centers for Disease Control and Prevention system (HR 1.69, 95% CI 1.14–2.50, p = 0.009) or jail hospital (HR 1.20, 95% CI 1.08–1.34, p = 0.001), and having a baseline CD4 count >350 cells/uL (HR 2.37, 95% CI 1.94–2.89. p < 0.001). Immunologic treatment failure was moderate to substantial among treated HIV patients. Providing second-line regimens and shifting treatment providers to professional hospitals should be considered to consolidate gains in averting morbidity and mortality.

Management of Hepatotoxicity in HIV-Infected Patients Treated with Combined Antiretroviral Therapy (cART): A Retrospective Cohort Study in Tianjin, China

Background: Liver diseases are among the most frequent causes of non-AIDS-related deaths in human immunodeficiency virus (HIV)-infected patients due to hepatitis B or C virus co-infections, and/or the toxicity of longterm treatment of some antiviral drugs. There are few cohort studies reported in China. Methods: All data from the clinic HIV/AIDS patients in the database of Tianjin Second People’s Hospital, a branch of the National Free Antiretroviral Treatment Program database, from April 1, 2010 to March 31, 2016 were retrospectively assessed and analyzed. Results: We analyzed 2270 HIV-positive, hepatitis B virus (HBV-), hepatitis C virus (HCV-) negative patients, who received cART and followed for 13334.8 person-years. A total of 67 patients (3.0%, or 5.0 per 1000 person-years) died of non-liver-related causes. The incidence of liver-related deaths in persons without HCV or HBV co-infections was zero percent during follow-up. Only 30 cases (1.3% or 2.2 per 1000 person-years) developed hepatotoxicity, but liver function of these patients improved after changing cART regimens. Conclusion: cART-related hepatotoxicity can be well-controlled and managed by modifying the therapeutic regimens. Liver-related mortality in HIV-positive, HBV-, HCV-negative patients is currently zero percent in Tianjin, China.

[Application of different death evaluation indicators for HIV/AIDS prevention and treatment].

AIDS has gradually changed from a fatal disease to a manageable chronic disease since the advent of antiretroviral drugs. In 2003, China initiated a national free antiretroviral treatment program for people living with HIV/AIDS, several death evaluation indicators have been used to evaluate public health effect of the program. Death evaluation indicators used frequently in domestic and overseas include mortality, case fatality rate, excess mortality, standard mortality ratio, years of potential life lost, disability-adjusted life year and life expectancy. This paper summarizes the different death indicators applied in effectiveness evaluation of HIV/AIDS prevention and treatment, elaborates the application range and significance of these indicators and suggests the research in related life expectancy and burden of disease which have not been conducted in China.

Effects of CD4 Cell Counts and Viral Load Testing on Mortality Rates in Patients With HIV Infection Receiving Antiretroviral Treatment: An Observational Cohort Study in Rural Southwest China.

Recent studies have suggested that CD4 cell count monitoring has little added value in patients who are virologically suppressed and immunologically stable if viral load (VL) testing is routinely available. These conclusions have not been directly assessed using mortality rate as a study end point in a real-world setting. This human immunodeficiency virus (HIV) treatment cohort study from 2008 to 2014 was conducted in Guangxi, China. We used a Cox regression model to analyze associations between the frequency of CD4 cell counts and VL testing and death. Compared with monitoring CD4 cell counts ≥3 times during the first year of antiretroviral therapy (ART) initiation, as currently suggested by the Chinese National Free Antiretroviral Treatment Program, monitoring them less than twice during the first year of ART was significantly associated with death; however, monitoring them twice in that year did not significantly increase mortality rates. Compared with testing VL at least once during the first year of ART, as currently suggested by the National Free Antiretroviral Treatment Program, performing no VL tests in the first year after ART initiation was significantly associated with higher mortality rates. Routine CD4 cell count monitoring did not have an impact on mortality rates among HIV-infected patients with VLs <1000 copies/mL or CD4 cell counts ≥350/μL beyond 12 months after ART initiation. Our study suggests that CD4 cell counts can be reduced to twice during the first year of ART and be reduced or stopped for patients who have achieved virologic suppression or immunologic stability after 12 months of treatment.