The burden of anemia among Chinese HIV-infected patients following the initiation of antiretroviral therapy in the treat-all era: a nationwide cohort study.

BACKGROUND: To assess the prevalence of anemia before and after antiretroviral therapy (ART) initiation and to identify impact of anemia on mortality among HIV-infected patients in China during the Treat-All era. METHODS: All HIV-infected patients who newly initiated ART between January 1, 2017 and December 31, 2020 were enrolled and followed up to December 31, 2021 in China. We analyzed the prevalence of anemia before and after ART initiation. Generalized estimating equations were fitted to determine factors associated with anemia after ART. Time-dependent cox proportional hazards models were performed to estimate the effect of anemia on death. RESULTS: Of 436,658 patients at the baseline of ART initiation, the overall prevalence of anemia was 28.6%. During a median 2.65 (IQR: 1.80-3.51) years of follow-up after ART initiation, 376,325 (86.2%) patients had at least one Hb measurement (a total of 955,300 hemoglobin measurements). The annual prevalence of anemia after ART was 17.0%, 14.1%, 13.4%, 12.6% and 12.7%, respectively. Being anemic at the baseline of ART initiation (adjusted odds ratio, aOR = 6.80, 95% confidence interval (CI): 6.67-6.92) was the strongest factor associated with anemia after ART. Anemia status after ART showed a strong association with death after multivariable adjustment (mild anemia: adjusted hazard ratio (aHR) = 2.65, 95% CI: 2.55-2.76; moderate anemia: aHR = 4.60; 95% CI:4.40-4.81; severe anemia: aHR = 6.41; 95% CI:5.94-6.91). CONCLUSIONS: In the era of ART universal access, pre-ART anemia was common among HIV-infected patients. Notably, a certain proportion of anemia still persisted after ART, and was significantly associated with death. We recommend strengthening the monitoring of patients at risk of anemia, especially in patients with baseline anemia or during the first year of ART, and timely treatment for correcting anemia.

Excess mortality and associated factors among people living with HIV initiating highly active antiretroviral therapy in Luzhou, China 2006-2020.

BACKGROUND: To estimate crude mortality, excess mortality, and standardized mortality rates (SMR) among people living with HIV (PLHIV) initiating highly active antiretroviral therapy (HAART) in Luzhou, China 2006-2020, and assess associated factors. METHODS: PLHIV initiating HAART in the HIV/AIDS Comprehensive Response Information Management System (CRIMS) in Luzhou, China 2006-2020 were included in the retrospective cohort study. The crude mortality, excess mortality, and SMR were estimated. Multivariable Poisson regression model was used for analyzing risk factors associated with excess mortality rates. RESULTS: The median age among 11,468 PLHIV initiating HAART was 54.5 years (IQR:43.1-65.2). The excess mortality rate decreased from 1.8 deaths/100 person-years (95% confidence interval [CI]:1.4-2.4) in 2006-2011 to 0.8 deaths/100 person-years (95%CI:0.7-0.9) in 2016-2020. SMR decreased from 5.4 deaths/100 person-years (95%CI:4.3-6.8) to 1.7 deaths/100 person-years (95%CI:1.5-1.8). Males had greater excess mortality with the eHR of 1.6 (95%CI:1.2-2.1) than females. PLHIV with CD4 counts ≥ 500 cells/µL had the eHR of 0.3 (95%CI:0.2-0.5) in comparison to those with CD4 counts < 200 cells/µL. PLHIV with WHO clinical stages III/IV had greater excess mortality with the eHR of 1.4 (95%CI:1.1-1.8). PLHIV with time from diagnosis to HAART initiation ≤ 3 months had the eHR of 0.7 (95%CI:0.5-0.9) compared to those with time ≥ 12 months. PLHIV with initial HAART regimens unchanged and viral suppression had the eHR of 1.9 (95%CI:1.4-2.6) and 0.1 (95%CI:0.0-0.1), respectively. CONCLUSIONS: The excess mortality and SMR among PLHIV initiating HAART in Luzhou, China decreased substantially from 2006 to 2020, but the mortality rate among PLHIV was still higher than general population. PLHIV who were male, with baseline CD4 counts less than 200 cells/µL, WHO clinical stages III/IV, time from diagnosis to HAART initiation ≥ 12 months, initial HAART regimens unchanged, and virological failure had a greater risk of excess deaths. Early and efficient HAART would be significant in reducing excess mortality among PLHIV.

A Universal Formation Mechanism of Hollow Multi-Shelled Structures Dominated by Concentration Waves.

Hollow multi-shelled structures (HoMS), a new family of hierarchical nano/micro-structured materials, have evoked intensive studies to discover their unique temporal-spatial ordering features. The theoretical understanding of the general synthetic methods of HoMS, i.e. the sequential templating approach (STA), makes it possible to understand, predict, and control the shell formation process. Herein, a mathematical model is established based on the experiment results, which reveal the appearance of concentration waves in the STA. The numerical simulation results not only correspond well to the experimental observations but also explain the regulation methods. Whereby, the underlying physical essence of STA is elucidated, suggesting that HoMS is the concrete representation of the concentration waves. Thereafter the formation of HoMS is not limited to the solid-gas reactions through high-temperature calcination, but could be extended to solution systems under low-temperature conditions.

Heterogeneous Hollow Multi-Shelled Structures with Amorphous-Crystalline Outer-Shells for Sequential Photoreduction of CO2.

Constructing delicate nano-/microreactors with tandem active sites in hierarchical architectures is a promising strategy for designing photocatalysts to realize the challenging but attractive CO2 reduction. Herein, hollow multi-shelled structure (HoMS) based microreactors with spatial ordered hetero-shells are fabricated, which achieve two-step CO2 -to-CH4 photoreduction. The multiple inner CeO2 shells increase the number of active catalytic sites to ensure efficient first-step reaction for generating CO, along with enriching the local CO concentration. The second-step CO-to-CH4 reaction is consequently induced by amorphous TiO2 (A-TiO2 ) composites on the adjacent outer-most shell, thus realizing the CO2 -to-CH4 conversion capability using one CeO2 @CeO2 /A-TiO2 HoMS. In-depth explorations in the microreactors provide compositional, structural, and interfacial guidance for engineering HoMS-based microreactors with temporally-spatially ordered shells toward efficient tandem catalysis.

PEG-Functionalized Hollow Multishelled Structures with On-Off Switch and Rate-Regulation for Controllable Antimicrobial Release.

The construction of responsive antimicrobial carriers with multifunctional and controllable release is an attractive but challenging proposition. Recently developed hollow multishelled structures (HoMSs) offers structural advantages, such as easily modifiable surfaces and mutually influenced shells. Herein, we report a novel pH-responsive antimicrobial carrier having hierarchical shells as multilevel responsive bodies using polyethylene glycol (PEG) as a gated regulator. The interaction between PEG-functionalized shells endows them with a pH-responsive switch and rate-regulator capability. These features are present in the form of rapid release of molecules wrapped in the outer shell, and controlled diffusion of antimicrobials stored in the inner shell by electrostatic interaction, resulting in a long-lasting mildew resistance for up to 71 days. The versatility of the hierarchical interactions of HoMSs will inspire the design of promising smart drug carriers.

Nationwide Cohort Study of Antiretroviral Therapy Timing: Treatment Dropout and Virological Failure in China, 2011-2015.

Background: People living with human immunodeficiency virus (PLWH) are still being diagnosed late, rendering the benefits of "early" antiretroviral therapy (ART) unattainable. Therefore, we aimed to evaluate the benefits of "immediate" ART. Methods: A nationwide cohort of PLWH in China who initiated ART January 1, 2011, to December 31, 2014 and had baseline CD4 results >200 cells/µL were censored at 12 months, dropout, or death, whichever came first. Treatment dropout and virological failure (viral load ≥400 copies/mL) were measured. Determinants were assessed by Cox and log-binomial regression. Results: The cohort included 123605 PLWH. The ≤30 days group had a significantly lower treatment dropout rate of 6.72%, compared to 8.91% for the 91-365 days group and to 12.64% for the >365 days group. The ≤30 days group also had a significantly lower virological failure rate of 5.45% (31-90 days: 7.39%; 91-365 days: 9.64%; >365 days: 12.67%). Greater risk of dropout (91-365 days: adjusted hazard ratio [aHR] = 1.33, 95% confidence interval [CI] = 1.25-1.42; >365 days: aHR = 1.55, CI = 1.47-1.54), and virological failure (31-90 days: adjusted risk ratio [aRR] = 1.35, CI = 1.26-1.45; 91-365 days: aRR = 1.66, CI = 1.55-1.78; >365 days: aRR = 1.85, CI = 1.74-1.97) were observed for those who delayed treatment. Conclusions: ART within 30 days of HIV diagnosis was associated with significantly reduced risk of treatment failure, highlighting the need to implement test-and-immediately-treat policies.

The Human Immunodeficiency Virus Care Continuum in China: 1985-2015.

Background: Human immunodeficiency virus (HIV) care continuum attrition is a major global public health challenge. Few studies have examined this problem in resource-limited settings. We aimed to assess cumulative, current, and historical achievement along China's HIV continuum of care. Methods: A nationwide, serial cross-sectional study of all individuals with HIV infection diagnosed in China between 1 January 1985 and 31 December 2015 was conducted using data from China's HIV/AIDS information systems. Biennial estimates of the number of persons living with HIV were also used. We defined 7 steps in HIV care continuum as infected (estimated), diagnosed, linked, retained, enrolled, receiving antiretroviral therapy (ART), and virally suppressed. Cumulative, 30-year performance, and biennial performance during the most recent 10 years were examined. Results: A total of 573529 persons diagnosed with HIV infection were included. Cumulatively, 94% were linked, 88% were retained, 73% were enrolled, 67% were receiving ART, and 44% were suppressed. Greatest attrition was observed for adolescents, minorities, and those who reported injecting drug use as their route of infection. Improvement was observed from 2005 to 2015. As of the end of 2015, 68% among those infected were diagnosed, 67% among diagnosed were receiving ART, and 65% among those receiving ART were virally suppressed. After adjusting for those without viral load testing, the proportion suppressed increased to 89%. Conclusions: Despite dramatic improvements, China faces serious challenges in achieving the Joint United Nations Programme on HIV/AIDS 90-90-90 targets, because of substantial attrition along its continuum of HIV care.

Cotrimoxazole prophylaxis and antiretroviral therapy: an observational cohort study in China.

OBJECTIVE: To assess if cotrimoxazole prophylaxis administered early during antiretroviral therapy (ART) reduces mortality in Chinese adults who are infected with human immunodeficiency virus (HIV). METHODS: We did a retrospective observational cohort study using data from the Chinese national free antiretroviral database. Patients older than 14 years who started ART between 1 January 2010 and 31 December 2012 and had baseline CD4+ T-lymphocyte (CD4+ cell) count less than 200 cells/µL were followed until death, loss to follow-up or 31 December 2013. Hazard ratios (HRs) for several variables were calculated using multivariate analyses. FINDINGS: The analysis involved 23 816 HIV-infected patients, 2706 of whom died during the follow-up. Mortality in patients who did and did not start cotrimoxazole during the first 6 months of ART was 5.3 and 7.0 per 100 person-years, respectively. Cotrimoxazole was associated with a 37% reduction in mortality (hazard ratio, HR: 0.63; 95% confidence interval, CI: 0.56-0.70). Cotrimoxazole in addition to ART reduced mortality significantly over follow-up lasting 6 months (HR: 0.65; 95% CI: 0.59-0.73), 12 months (HR: 0.58; 95% CI: 0.49-0.70), 18 months (HR: 0.49; 95% CI: 0.38-0.63) and 24 months (HR: 0.66; 95% CI: 0.48-0.90). The mortality reduction was evident in patients with baseline CD4+ cell counts less than 50 cells/µL (HR: 0.60; 95% CI: 0.54-0.67), 50-99 cells/µL (HR: 0.66; 95% CI: 0.56-0.78) and 100-199 cells/µL (HR: 0.78; 95% CI: 0.62-0.98). CONCLUSION: Cotrimoxazole prophylaxis started early during ART reduced mortality and should be offered to HIV-infected patients in low- and middle-income countries.

Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (2003-11): a national observational cohort study.

BACKGROUND: On the basis of the results of the randomised clinical trial HPTN 052 and observational studies, WHO has recommended that antiretroviral therapy be offered to all HIV-infected individuals with uninfected partners of the opposite sex (serodiscordant couples) to reduce the risk of transmission. Whether or not such a public health approach is feasible and the outcomes are sustainable at a large scale and in a developing country setting has not previously been assessed. METHODS: In this retrospective observational cohort study, we included treated and treatment-naive HIV-positive individuals with HIV-negative partners of the opposite sex who had been added to the national HIV epidemiology and treatment databases between Jan 1, 2003 and Dec 31, 2011. We analysed the annual rate of HIV infection in HIV-negative partners during follow-up, stratified by treatment status of the index partner. Cox proportional hazards analyses were done to examine factors related to HIV transmission. FINDINGS: Based on data from 38,862 serodiscordant couples, with 101,295·1 person-years of follow-up for the seronegative partners, rates of HIV infection were 2·6 per 100 person-years (95% CI 2·4-2·8) among the 14,805 couples in the treatment-naive cohort (median baseline CD4 count for HIV-positive partners 441 cells per µl [IQR 314-590]) and 1·3 per 100 person-years (1·2-1·3) among the 24,057 couples in the treated cohort (median baseline CD4 count for HIV-positive partners 168 cells per µl [62-269]). We calculated a 26% relative reduction in HIV transmission (adjusted hazard ratio 0·74, 95% CI 0·65-0·84) in the treated cohort. The reduction in transmission was seen across almost all demographic subgroups and was significant in the first year (0·64, 0·54-0·76), and among couples in which the HIV-positive partner had been infected by blood or plasma transfusion (0·76, 0·59-0·99) or heterosexual intercourse (0·69, 0·56-0·84), but not among couples in which the HIV-positive partner was infected by injecting drugs (0·98, 0·71-1·36). INTERPRETATION: Antiretroviral therapy for HIV-positive individuals in serodiscordant couples reduced HIV transmission across China, which suggests that the treatment-as-prevention approach is a feasible public health prevention strategy on a national scale in a developing country context. The durability and generalisability of such protection, however, needs to be further studied. FUNDING: Chinese Government's 12th Five-Year Plan, the National Natural Science Foundation of China, and the Canadian International Development Research Centre.

Incidence and associated factors of pulmonary tuberculosis in HIV-infected children after highly active antiretroviral therapy (HAART) in China: a retrospective study.

China is a country with high tuberculosis (TB) incidence but relatively low HIV prevalence. However, due to difficulties in diagnosis and reporting, true burden of HIV-associated TB in children is unknown. The objective of this study was to describe the incidence of pulmonary TB (PTB) after antiretroviral therapy (ART) and to study risk factors. A retrospective study was performed based on routinely collected data from China national pediatric free antiretroviral treatment database. A total of 3365 children under 15 years on ART from July 2005 to October 2012 were included. Multivariable logistic regression was used to detect associated factors. Two thousand nine hundred and ninety (89%) children got infected from HIV-positive mother, with median age of 6.7 (4.1, 10.0) years at highly active antiretroviral therapy (HAART) initiation in this program. Seventy-seven (2.3%) children were diagnosed with PTB after ART during 7.3 years cohort observation. Median time of occurrence was 212 (30-514) days. Overall incidence was 0.83 (0.65-1.01)/100 person-years (py), with the peak of 3.6/100 py in the first 3 months after antiretroviral treatment. WHO stage IV at baseline showed 2 (95% CI 1.0-6.8) times more risk for developing TB. Late clinical stage at ART initiation was shown to relate with TB incidence. PTB coinfection leads to higher mortality. Early diagnosis and treatment of HIV are highly required to reduce HIV-associated morbidity and mortality due to TB.

Mesoscience in Hollow Multi-Shelled Structures.

The prevalence of mesoscale complexity in materials science underscores the significance of the compromise in competition principle, which gives rise to the emergence of mesoscience. This principle offers valuable insights into understanding the formation process, characteristics, and performance of complex material systems, ultimately guiding the future design of such intricate materials. Hollow multi-shelled structures (HoMS) represent a groundbreaking multifunctional structural system that encompasses several spatial regimes. A plethora of mesoscale cases within HoMS present remarkable opportunities for exploring, understanding, and utilizing mesoscience, varying from the formation process of HoMS, to the mesoscale structural parameters, and finally the distinctive mass/energy transfer behaviors exhibited by HoMS. The compromise in competition between the diffusion and reaction contributes to the successful formation of multi-shells of HoMS, allowing for precise regulation of the structural parameters by dynamically varying the interplay between two dominances. Moreover, the distinct roles played by the shells and cavities within HoMS significantly influence the energy/mass transfer processes with the unique temporal-spatial resolution, providing guidance for customizing the application performance. Hopefully, the empirical and theoretical anatomy of HoMS following mesoscience would fuel new discoveries within this promising and complex multifunctional material system.

Rational Design of Coordination Polymers Composited Hollow Multishelled Structures for Drug Delivery.

Multifunctional drug delivery systems (DDS) are in high demand for effectively targeting specific cells, necessitating excellent biocompatibility, precise release mechanisms, and sustained release capabilities. The hollow multishelled structure (HoMS) presents a promising solution, integrating structural and compositional design for efficient DDS development amidst complex cellular environments. Herein, starting from a Fe-based metal-organic framework (MOF), amorphous coordination polymers (CP) composited HoMS with controlled shell numbers are fabricated by balancing the rate of MOF decomposition and shell formation. Fe-CP HoMS loaded with DOX is utilized for synergistic chemotherapy and chemodynamic therapy, offering excellent responsive drug release capability (excellent pH-triggered drug release 82% within 72 h at pH 5.0 solution with doxorubicin (DOX) loading capacity of 284 mg g-1). In addition to its potent chemotherapy attributes, Fe-CP-HoMS possesses chemodynamic therapy potential by continuously catalyzing H2O2 to generate ·OH species within cancer cells, thus effectively inhibiting cancer cell proliferation. DOX@3S-Fe-CP-HoMS, at a concentration of 12.5 µg mL-1, demonstrates significant inhibitory effects on cancer cells while maintaining minimal cytotoxicity toward normal cells. It is envisioned that CP-HoMS could serve as an effective and biocompatible platform for the advancement of intelligent drug delivery systems in the realm of cancer therapy.

Treatment failure and associated factors among people living with HIV on highly active antiretroviral therapy in mainland China: A systematic review and meta-analysis.

OBJECTIVE: Reducing the prevalence of treatment failure among people living with HIV (PLHIV) on highly active antiretroviral therapy (HAART) is crucial for improving individual health and reducing disease burden. This study aimed to assess existing evidence on treatment failure and its associated factors among PLHIV in mainland China. METHODS: We conducted a comprehensive search of PubMed, Web of Science, Cochrane Library, WanFang, China National Knowledge Infrastructure, and SinoMed databases. Relevant studies on treatment failure among PLHIV in mainland China until September 2022 were searched, including cross-sectional, case-control, and cohort studies. The primary outcome was treatment failure, and secondary outcomes were the potential influencing factors of treatment failure. We performed a meta-analysis to pool each outcome of interest, including meta-regression, subgroup, publication bias, and sensitivity analyses. RESULTS: A total of 81 studies were deemed eligible and included in the final meta-analysis. The pooled treatment failure prevalence among PLHIV in mainland China was 14.40% (95% confidence interval [CI]:12.30-16.63), of which the virological and immunological failure prevalence was 10.53% (95%CI:8.51-12.74) and 18.75% (95%CI:15.44-22.06), respectively. The treatment failure prevalence before and after 2016 was 18.96% (95%CI:13.84-24.67) and 13.19% (95%CI:10.91-15.64). Factors associated with treatment failure included good treatment adherence (odds ratio [OR] = 0.36, 95%CI:0.26-0.51), baseline CD4 counts>200 cells/µL (OR = 0.39, 95%CI:0.21-0.75), HAART regimens containing Tenofovir Disoproxil Fumarate (TDF) (OR = 0.70, 95%CI:0.54-0.92), WHO clinical stage III/IV (OR = 2.02, 95%CI:1.14-3.59) and age≥40 years (OR = 1.56, 95%CI:1.23-1.97). CONCLUSION: The prevalence of treatment failure among PLHIV receiving HAART in mainland China was low and tended to decline. Poor adherence, low baseline CD4 count, HAART regimens without TDF, advanced clinical stage, and old age were contributing factors for treatment failure. Relevant intervention programs are needed with increasing treatment adherence through behavioral intervention or precise intervention targeting older adults.

Changing Mortality and Patterns of Death Causes in HIV Infected Patients - China, 2013-2022.

What is already known about this topic?: The advent of antiretroviral therapy (ART) has markedly decreased mortality rates among patients infected with human immunodeficiency virus (HIV). Globally, there has been a 43% reduction in acquired immunodeficiency syndrome (AIDS)-related deaths from 2010 to 2022. Additionally, prior research indicates that the initiation of ART at an early stage within China has substantially lowered mortality rates. What is added by this report?: Over the previous decade, following the implementation of China's universal ART access strategy, the patterns of mortality causes among HIV-infected individuals across the country have undergone significant alterations. In 2022, the all-cause mortality rate among this population was reported at 2.7%, with the non-AIDS-related mortality rate at 1.8%. However, it is important to consider that the accuracy of death reporting could contribute to potential misclassification of the underlying causes of death. What are the implications for public health practice?: Efforts to enhance health outcomes should persist in emphasizing the advancement of ART strategies, with a particular focus on mitigating non-AIDS-related mortality in the future.

Hollow Nanomaterials in Advanced Drug Delivery Systems: From Single- to Multiple Shells.

Hollow-structured nanomaterials (HSNMs) have attracted increased interest in biomedical fields, owing to their excellent potential as drug delivery systems (DDSs) for clinical applications. Among HSNMs, hollow multi-shelled structures (HoMSs) exhibit properties such as high loading capacity, sequential drug release, and multi-functionalized modification and represent a new class of nanoplatforms for clinical applications. The remarkable properties of HoMS-based DDS can simultaneously satisfy and enhance DDSs for delivering small molecular drugs (e.g., antibiotics, chemotherapy drugs, and imaging agents) and macromolecular drugs (e.g., protein/peptide- and nucleic acid-based drugs). First, the latest research advances in delivering small molecular drugs are summarized and highlight the inherent advantages of HoMS-based DDSs for small molecular drug targeting, combining continuous therapeutic drug delivery and theranostics to optimize the clinical benefit. Meanwhile, the macromolecular drugs DDSs are in the initial development stage and currently offer limited delivery modes. There is a growing need to analyze the deficiency of other HSNMs and integrate the advantages of HSNMs, providing solutions for the safe, stable, and cascade delivery of macromolecular drugs to meet vast treatment requirements. Therefore, the latest advances in HoMS-based DDSs are comprehensively reviewed, mainly focusing on the characteristics, research progress by drug category, and future research prospects.

Monitoring HIV drug resistance using early warning indicators in China: results from a pilot survey conducted in 2008.

Robust programmatic monitoring of factors associated with the emergence of human immunodeficiency virus (HIV) drug resistance is an essential component of antiretroviral therapy (ART) program evaluation and treatment optimization. China piloted World Health Organization HIV drug resistance early warning indicators to assess the feasibility and usefulness of results. Overall, early warning indicator monitoring showed high levels of appropriate ART prescribing, low rates of loss to follow-up 12 months after ART initiation, and high rates of retention of first-line ART at 12 months. On-time drug pick-up, which may signal treatment interruptions, was identified as a challenge. HIV drug resistance early warning indicator monitoring provides a valuable assessment of ART service delivery, and its application will be scaled up throughout China.

Hollow structures as drug carriers: Recognition, response, and release.

Hollow structures have demonstrated great potential in drug delivery owing to their privileged structure, such as high surface-to-volume ratio, low density, large cavities, and hierarchical pores. In this review, we provide a comprehensive overview of hollow structured materials applied in targeting recognition, smart response, and drug release, and we have addressed the possible chemical factors and reactions in these three processes. The advantages of hollow nanostructures are summarized as follows: hollow cavity contributes to large loading capacity; a tailored structure helps controllable drug release; variable compounds adapt to flexible application; surface modification facilitates smart responsive release. Especially, because the multiple physical barriers and chemical interactions can be induced by multishells, hollow multishelled structure is considered as a promising material with unique loading and releasing properties. Finally, we conclude this review with some perspectives on the future research and development of the hollow structures as drug carriers.

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

OBJECTIVES: High 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. METHODS: We 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. RESULTS: Of 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]). CONCLUSIONS: The 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.

Some patient-related factors associated with late access to ART in China's free ART program.

Highly active antiretroviral therapy (HAART) has become widely available in China during the past seven years. However, many patients still initiate treatment at very late stages. To understand the distribution of baseline CD4 and factors associated with late antiretroviral therapy (ART) access, the National Free ART Database was retrospectively reviewed and a total of 49,321 HIV/AIDS patients were identified in this study based on the following inclusion criteria: (1) age ≥18; (2) initiated HAART between 1 July, 2006 and 31 December, 2009; (3) have recorded baseline CD4 cell count. This study showed that although both the median and mean baseline CD4 increased consistently over the study period, there were still about 30% of HIV/AIDS patients accessing ART at a very late stage (CD4 ≤ 50 µl) in 2009. Risk factors for late ART access included being male, single, having a short time interval between HIV diagnosis and treatment, and being infected through heterosexual contact. Being infected through injection drug use and homosexual contact were protective. Transmission route and marriage status showed different effects in a gender stratified analysis. A strengthened HIV testing and screening program is the key to improving the accessibility of ART and populations that are vulnerable to sexual transmission of HIV should be the primary target of the program.

Predictors of virologic failure in HIV-1-infected adults receiving first-line antiretroviral therapy in 8 provinces in China.

BACKGROUND: Despite poor primary health care systems, free antiretroviral therapy (ART) has been available in China for >5 years. Virologic outcomes in Chinese patients receiving ART have not been described on a national level. METHODS: A multistage cluster design was used in 8 provinces to randomly select patients who had been receiving first-line ART for at least 6 months, who were stratified into 3 treatment-duration groups. Viral load testing and patient interviews were conducted, and data were linked with national treatment database information. Collected data were analyzed for association with viral suppression by means of multivariate modeling. Adequate viral suppression was defined as a viral load of <400 copies/mL. RESULTS: Of 5256 patients receiving ART, 3894 met the eligibility criteria, among whom 1153 were analyzed. Overall, 72% demonstrated viral suppression, and 82%, 73%, and 67% of the participants receiving ART for 6-11, 12-23, and > or = 24 months, respectively, experienced viral suppression (P < .001). In a multivariate model, treatment given at locations other than county-level hospitals was less likely to achieve viral suppression, with greater odds for inadequate virologic response found at village clinics (odds ratio [OR], 5.4; 95% confidence interval [CI], 2.9-10.1), township health centers (OR, 3.1; 95% CI, 1.7-5.6), and public health clinics (OR, 3.1; 95% CI, 1.7-5.6). Patients receiving didanosine-based regimens were more likely to experience an inadequate virologic response than were those receiving lamivudine-based regimens (OR, 3.9; 95% CI, 2.7-5.7). CONCLUSIONS: China's national ART program is largely successful at suppressing viral load. Care received outside of hospitals and regimens containing didanosine were associated with less favorable virologic outcomes.