Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study.

BACKGROUND: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. METHODS: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. RESULTS: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. CONCLUSIONS: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.

A new dual-targeting real-time RT-PCR assay for hepatitis D virus RNA detection.

In this study, a real-time reverse transcription-polymerase chain reaction (real time RT-PCR) assay targeting 2 genetic segments was established to detect HDV RNA. Utilizing the World Health Organization International Standard for Hepatitis D Virus RNA, the lower limit of detection was 575 IU/mL, and the linearity of quantification ranged from 575,000 IU/mL to 575 IU/mL. 384 HBsAg-positive samples collected from China were tested by this method and HDV antibody detection. Eleven samples were positive for anti-HDV IgG which may persist after HDV resolution, 6 samples were HDV RNA positive, and 5 samples were positive for anti-HDV IgM. This assay showed more sensitivity than the detection of anti-HDV IgM. These data demonstrate that the real-time RT-PCR assay for HDV RNA could be implemented in the clinical detection of HDV infection in chronic HBV-infected patients in China.

Efficacy and Safety of Tenofovir and Lamivudine in Combination with Efavirenz in Patients Co-infected with Human Immunodeficiency Virus and Hepatitis B Virus in China.

BACKGROUND: The prevalence of hepatitis B virus (HBV) infection is high among individuals infected with human immunodeficiency virus (HIV) in China. Both HIV and HBV can be treated with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC), so we evaluated the safety and efficacy of combination antiretroviral therapy (ART) that included TDF, 3TC, and efavirenz (EFV) among ART-naive individuals who were co-infected with HIV and HBV. METHODS: One hundred HIV/HBV co-infected ARV-naive individuals were started on the regimen of TDF, 3TC, and EFV, and the levels of plasma HBV DNA, HIV RNA, and biochemical evaluation related to the function of liver and kidney were analyzed. RESULTS: Concerning efficacy, this study found that by week 48, the vast majority co-infected participants receiving this ART regimen had undetectable HBV DNA levels (71%) and/or HIV RNA levels (90%). Concerning safety, this study found that the median estimated glomerular filtration rate of participants decreased from baseline (109 ml·min-1·1.73 m-2) to week 12 (104 ml·min-1·1.73 m-2) but was almost back to baseline at week 48 (111 ml·min-1·1.73 m-2). CONCLUSION: This combination ART regimen is safe and effective for patients with HIV/HBV co-infection. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01751555; https://clinicaltrials.gov/ct2/show/NCT01751555.

[Specific causes of death among 381 AIDS patients who died in hospitals].

OBJECTIVE: In this study, researchers investigated the demographic and clinical characteristics of AIDS patients who died in hospitals, analyzed the specific causes of death, and looked for the correlation between specific cause of death and their clinical characteristics. METHODS: Data of clinical characteristics of patients and their specific causes AIDS of death who died in the seven hospitals from 2009 to 2010 were collected retrospectively. All the specific causes of death were classified according to the Cause of Death (CoDe) project protocol. Univariate analysis and multivariate logistic regression analysis were used to find the association between some categorical variables and the risk for AIDS patients died from AIDS related illnesses. RESULTS: Clinical characteristics and the cause of death of the 381 deceased in seven hospitals in this study were collected. 82.4% were male, with priority as 30-45 years old. 123 (32.3%) death patients had received ART before death. In all death cases, the cause of death of 252 patients (66.1%) were due to AIDS related diseases, with opportunistic infections the most (92.4%). Tubercle bacillus, infection of Penicillium marneffei and Pneumocystis jiroveci were the three leading causes of opportunistic infection deaths. Of 129 patients who died of non-AIDS related disease, non-AIDS infection (29.5%), hepatitis (22.5%), and non-AIDS malignancy(10.1%)were the first three causes of death. The cause of death in patients who had injecting drug use behavior within one year, had not received ART or not long enough, with opportunistic infections, without hepatitis, with the last low CD4 cell counts before death etc. were tend to due to AIDS related disease. CONCLUSION: Opportunistic infections, non-AIDS related infections and hepatitis were the three leading causes of death in this study. The duration of time on ART had impact on the patient's cause of death. The HIV infected patients who had received ART before death had more risk to die of non-AIDS related disease, compared to patients who had not. The longer time they had accessed to ART, the less likely they would die on non-AIDS related illnesses.

Expansion of China's free antiretroviral treatment program.

BACKGROUND: In 2003, China's National Free Antiretroviral Treatment Program (NFATP) was initiated as a pilot, which covered only 100 HIV/AIDS patients. By 2011, the pilot had evolved into a nationwide program and had provided free treatment for over 150 000 patients. The objective of this study was to report and evaluate the progress of China's free antiretroviral treatment program. METHODS: The NFATP Database was systematically reviewed and a total of 150 692 HIV/AIDS patients were included in this study. Program progress indicators including the number of treated HIV/AIDS patients, follow-up visit rate, CD4 test rate, and viral load test rate were summarized and examined over a calendar year to evaluate the progress of NFATP quantitatively and qualitatively. RESULTS: By the end of 2011, a total of 150 692 HIV/AIDS patients had been treated through the NFATP and 122 613 of them were still on treatment. Of all patients, about 72% were enrolled during the past four years. The dominant transmission route was blood related in the early phase of the NFATP, but gradually changed to sexual contact. Besides quantitative improvements, progress indicators also demonstrated significant qualitative improvements that the program had made during the past 9 years. CONCLUSIONS: Great achievement has been made by China's NFATP. China's experience indicates the importance of a comprehensive response to the success of its treatment program. However, to ensure the quality and sustainability of treatment in the long term, more attention and resources should be paid towards program management.

Pregnancy outcomes and risk factors for low birth weight and preterm delivery among HIV-infected pregnant women in Guangxi, China.

BACKGROUND: Six provinces in China accounted for 70% - 80% of all reported HIV/AIDS cases in the country in 2009 and five provinces accounted for 78% of all reported mother-to-child transmission (MTCT) of HIV cases. Because Guangxi belonged to both groups, the Prevention of Mother-to-Child Transmission (PMTCT) Plus program was established there to understand better low birth weight (LBW) and preterm delivery (PD) birth outcomes and their associated risk factors better. METHODS: Pregnancy outcomes were examined among HIV-infected pregnant women who enrolled in the PMTCT Plus program from June 2006 to February 2009 in Guangxi, China. Multivariate Logistic regression analysis was used to explore the risk factors associated with LBW (< 2500 g) and PD (gestational age < 37 weeks). RESULTS: The prevalence of LBW and PD among 194 HIV-positive mothers was 19.6% (38/194) and 9.8% (19/194), respectively. Multivariate Logistic regression analysis showed that CD4 cell count < 100 cell/µl (multivariate-adjusted odds ratio (AOR) 5.52; 95%CI 1.11 - 25.55) and CD4 cell count 100 - 199 cells/µl (AOR 3.40; 95%CI 1.03 - 11.25, compared to CD4 cell count ≥ 350 cells/µl), gestational age < 37 weeks (AOR 4.38; 95%CI 1.29 - 14.82, compared to ≥ 37 weeks), maternal weight < 45 kg (AOR 5.64; 95%CI 1.09 - 29.07) and maternal weight 45 - 54 kg (AOR 3.55; 95%CI 1.31 - 9.60, compared to ≥ 55 kg) at enrollment, and HIV RNA ≥ 100 000 copies/ml at enrollment (AOR 4.22; 95%CI 1.24 - 14.32) and 20 000 - 99 999 (AOR 2.77; 95%CI 1.01 - 7.77, compared to < 20 000 copies/ml) were associated with a higher risk of LBW. For PD, only maternal injection drug use as the route of HIV transmission (AOR 5.30; 95%CI 1.33 - 21.14, compared to those infected with HIV through sexual transmission) was significantly associated with a higher risk of PD. CONCLUSIONS: Lower CD4 cell count and higher HIV RNA viral load at enrollment were associated with LBW. Optimal antenatal care, including earlier antenatal screening and HIV diagnosis, is critical to earlier PMTCT prophylaxis and/or HIV treatment to prevent transmission of HIV to the infant and also to prevent LBW pregnancy outcomes.

Engaging HIV-infected patients in antiretroviral therapy services: CD4 cell count testing after HIV diagnosis from 2005 to 2009 in Yunnan and Guangxi, China.

BACKGROUND: The initiation and expansion of China's national free antiretroviral therapy program has led to significant improvement of survival among its participants. Success of further scaling up treatment coverage rests upon intensifying HIV screening and efficient linkage of care. Timely CD4 cell count testing after HIV diagnosis is necessary to determine whether a patient meets criteria for antiretroviral treatment, and represents a crucial link to engage HIV-infected patients in appropriate care, which has not been evaluated in China. METHODS: We evaluated all patients ≥ 16 years who tested HIV positive from 2005 to 2009 in Yunnan and Guangxi. Multivariate Logistic regression models were applied to identify factors associated with lack of CD4 cell count testing within 6 months after HIV diagnosis. RESULTS: A total of 83 556 patients were included. Over the study period, 30 635 (37%) of subjects received a CD4 cell count within 6 months of receiving the HIV diagnosis. The rate of CD4 cell count testing within 6 months of HIV diagnosis increased significantly from 7% in 2005 to 62% in 2009. Besides the earlier years of HIV diagnosis, negative predictors for CD4 cell count testing in multivariate analyses included older age, not married or unclear marriage status, incarceration, diagnosis at sexual transmitted disease clinics, mode of HIV transmission classified as men who have sex with men, intravenous drug users or transmission route unclear, while minority ethnicity, receipt of high school or higher education, diagnosis at voluntary counseling and testing clinics, and having HIV positive parents were protective. CONCLUSIONS: Significant progress has been made in increasing CD4 testing among newly diagnosed HIV positive patients in Yunnan and Guangxi from 2005 - 2009. However, a sizable proportion of HIV positive patients still lack CD4 testing within 6 months of diagnosis. Improving CD4 testing, particularly among patients with identified risk factors, is essential to link patients with ART services and optimize treatment coverage.

[Expression of CD38 and HLA-DR on CD8+ T cells in pediatric AIDS patients receiving highly active antiretroviral therapy (HAART)].

OBJECTIVE: To study the expression of CD38 and HLA-DR on CD8(+) T cells in pediatric AIDS patients receiving highly active antiretroviral therapy (HAART) and the relationship of immune activation and disease progression. METHODS: A cross-section study of 194 pediatric AIDS patients receiving HAART was carried out and 52 age-matched healthy children were recruited as control. The percentage of CD4(+), CD8(+), CD8(+)/CD38(+) and CD8(+)/HLA-DR(+) T cells was tested using flow cytometry, and HIV-RNA in plasma was detected by quantitative RT-PCR. RESULTS: One hundred and ninety-four pediatric AIDS patients were divided into two groups according to the viral load: 59 patients with VL ≥ 400 copies/ml and 135 patients with VL < 400 copies/ml. The percentage of CD8(+)/CD38(+) and CD8(+)/HLA-DR(+) T cells of patients with VL ≥ 400 copies/ml was significantly higher than that of patients with VL < 400 copies/ml (P < 0.05). Of patients with VL < 400 copies/ml, the percentage of CD8(+)/CD38(+) T cells was nearly normal, and the percentage of CD8(+)/HLA-DR(+) T cells was higher than normal level (P < 0.05). There was a positive correlation between percentage of CD8(+)/CD38(+) and of CD8(+)/HLA-DR(+)T cells and viral load (R = 0.403, P = 0.03 for the former and R = 0.569, P = 0.09 for the later). CONCLUSIONS: Effective HAART could decrease immune activation of HIV-infected children significantly. And there was a positive correlation between percentage of CD8(+)/CD38(+) and of CD8(+)/HLA-DR(+)T cells and viral load, suggesting that the two indicators might be used as the substitution of viral load in resource-limited areas.

Diagnosis of pulmonary tuberculosis among asymptomatic HIV+ patients in Guangxi, China.

BACKGROUND: Pulmonary tuberculosis (PTB) among asymptomatic Chinese patients with HIV infection has not been investigated despite high tuberculosis burden in China. This study was aimed to evaluate the prevalence, risk factors and clinical outcomes of PTB among asymptomatic patients with HIV/AIDS in Guangxi to facilitate the development of diagnostic and treatment strategies. METHODS: All asymptomatic adult HIV-infected patients with CD4 < 350 cells/µl who attended four HIV clinics in Guangxi between August 2006 and March 2008 were evaluated for active PTB with physical examination, chest X-ray (CXR), sputum smear and/or sputum liquid culture. Data were described using median (interquartile range, IQR) and frequencies. Univariate and multivariate Logistic regression analyses were performed to identify risk factors associated with PTB. RESULTS: Among 340 asymptomatic subjects, 15 (4%) were diagnosed with PTB, with 4 (27%) sputum smear positive and 8 (53%) sputum culture positive. CXR has higher diagnostic sensitivity (87%) than sputum smear (25%) and sputum culture (67%), but lower specificity (56%) compared with sputum smear (99%) and culture (100%). In univariate analysis, injection drug user, body mass index (BMI) < 18 kg/m(2), CD4 < 50 cells/µl and presence of peripheral lymphadenopathy were associated with an increased risk of asymptomatic PTB, while in multivariate analysis only peripheral lymphadenopathy maintained statistical significance (OR = 7.6, 95%CI 1.4 - 40). Patients with negative smear and minor or no abnormalities on CXR had longer interval between screening and TB treatment. CONCLUSIONS: PTB was relatively common in this group of HIV(+) asymptomatic Chinese patients. Diagnosis is challenging especially where sputum culture is unavailable. These findings suggest that an enhanced evaluation for PTB needs to be integrated with HIV care in China and transmission prevention in China to control at both households and health care facilities, especially for patients with factors associated with a higher risk of PTB.

[Study on the quality of life and influencing factors among people living with AIDS].

OBJECTIVE: Studing the main influencing risk factors to provide evidence for improving the quality of life among people living with HIV. METHODS: The quality of life on 758 patients with HIV was evaluated by the Medical Outcomes Study Short-Form Health Survey (SF-36) and some potential risk factors as personal characteristics and disease condition were studied. Means and standard deviations of data were calculated and differences among groups and variances were tested using Student's t test, followed by step-wise multivariate regression. RESULTS: The SF-36 two summary scores of 758 patients with HIV appeared to be 45.34 +/- 8.77 and 41.92 +/- 12.01 respectively. The physical component summary scores (PCS) had a gradual decrease with the increase of age. However, mental component summary scores (MCS) had a gradual decrease with the increase of time receiving the treatment. Male patients reported having a better quality of life (QOL) than female, and patients who were infected through injecting drug use and sexual transmission reported to have had better QOL than patients who were infected through paid blood plasma donation. Compare to patients having low CD4+ count, those having higher CD4+ count reported to have better QOL. CONCLUSION: Patients being young, female, infected through paid blood plasma donation, having low CD+ count, or treated for longer period, would have unsatisfactory QOL.

Different plasma levels of interleukins and chemokines: comparison between children and adults with AIDS in China.

BACKGROUND: The immunological differences between children and adults with AIDS in China are not well documented. Th1/Th2 cytokines and chemokines are two types of immune factors intimately involved in disease progression of HIV-1 infection. This study aimed to identify changes in plasma levels of Th1/Th2 cytokines inerleukin (IL)-18, IL-16, IL-10 and chemokines regulated on activation, normal T cell expressed and secreted (RANTES), stromal cell-derived factor-1 (SDF-1) and monocyte chemoattractant protein-1 (MCP-1) in HIV-1-infected children and adults in China. METHODS: Seventy-five children with AIDS and 35 adult AIDS patients were recruited and clinical data were collected. CD4(+) T lymphocyte counts were measured by flow cytometery and plasma HIV RNA levels were measured by quantitative RT-PCR. Plasma levels of IL-18, IL-10, IL-16, RANTES, MCP-1, SDF-1alpha and SDF-1beta were quantified by enzyme-linked immunosorbent assay. The levels of beta2-microglobulin (beta2-MG) and soluble Fas (sFas) were measured to validate the level of humoral and cellular immune activation. RESULTS: The mean levels of all cytokines in pediatric and adult AIDS patients were significantly higher than in their healthy controls (P < 0.01). The mean levels of these cytokines were higher in pediatric patients than in adult patients (P < 0.05, except for SDF-1alpha and beta2-MG). Some of the cytokine levels in patients younger than 6 years old was higher than in older children and adults with AIDS (IL-10, IL-18, SDF-1alpha, MCP, RANTES and sFas, P < 0.05). Levels of IL-18, IL-10, RANTES and beta2-MG of pediatric patients increased as the levels of viral load increased (P < 0.05). CONCLUSIONS: Abnormal immune activation can be measured in Chinese pediatric and adult patients with AIDS, and is higher in children than in adult patients. The cytokines levels coincide with disease progression of AIDS, but have no direct relationship with total CD4(+) T cell count.

[Clinical features of 66 children with acquired immunodeficiency syndrome].

OBJECTIVE: To study the clinical features of pediatric acquired immunodeficiency syndrome(AIDS). METHODS: The epidemiological, clinical and laboratory data of 66 children with AIDS were retrospectively studied. RESULTS: Of the 66 patients, 46 (69.7%) were male and 20 (30.3%) were female, with a mean age of 8.7 years (ranged 2-16 years). The mean age at diagnosis was 7.7 years (ranged 2-15 years). Vertical transmission as the route of infection was documented in 48 cases (72.7%). Fourteen children (21.2%) were infected through blood or blood products. The route of infection could not be identified in 4 cases (6.1%). Body weight loss was noted in 43 cases (65.2%), anemia in 42 cases (63.7%), fever in 40 cases (60.6%), fatigue in 38 cases (57.6%), rash in 31 cases (47.0%), chronic cough in 28 cases (12.1%), chronic diarrhea in 24 cases (36.4%), CNS involvement in 16 cases (24.2%), oral thrush in 13 cases (19.7%), and hepatosplenomegaly in 12 cases (18.2%). Body height of 30 cases (45.4%) and body weight of 26 cases (39.4%) ranked the lower level. The immune system was severely suppressed in 59 cases (89.4%) and moderately suppressed in 7 cases (10.6%). CONCLUSIONS: Vertical transmission remained the most common route of pediatric HIV infection. There were various clinical manifestations in children with AIDS. The immune systems of the majority of children with this disorder were severely suppressed.

[A retrospective cohort study on reduction of AIDS mortality among patients enrolled in national-free antiretroviral treatment programme in two cities in China].

OBJECTIVE: To determine the effect of national free highly active antiretroviral treatment (HAART) on reduction of mortality and relevant risk factors among adult Acquired immunodeficiency syndrome (AIDS) patients. METHODS: A retrospective cohort study was conducted and all AIDS patients diagnosed before Aug. 30th, 2008 in Zhumadian, Henan province, and Fuyang, Anhui province were enrolled in this study, where HAART initiated in early time. The data and information were collected such as AIDS progress, diagnosis, treatment, death and et al. RESULTS: Among 10,394 AIDS patients, the mean age was (41.7 +/- 9.3) year-old, 50.3% (5233/10,394) were male, 85.0% (8808/10,394) were married, 95.1% (9880/10,394) were farmers, and 81.2% (8438/10,394) were former plasma donors (FPDs). The coverage of HAART increased from 5.2% in 2002 to 66.5% in 2008. Conversely, the overall mortality declined from 35.4/100 person-years in 2002 to 5.9/100 person-years in 2008. In a multivariate Cox proportional hazards analysis, the greatest risk factor for mortality was non-HAART, with a hazard ratio (HR) 4.3 (95%CI: 4.0 - 4.7). Among treated patients, compared with higher CD(4)(+) T cell counts (> 200 cells/microl), those initiating therapy with lower CD(4)(+) T cell counts, were at greater risk to death (< 50 cells/microl, HR = 7.9; 50 - 199 cells/microl, HR = 2.8). Number of opportunistic infections (OIs) was risk to mortality (HR = 2.1). In addition, other risk factors included male, age (>or= 50 years old), and other infection way except FPDs (HR were 1.4, 1.6 and 1.8). CONCLUSION: The national free treatment program has significantly reduced the AIDS mortality rate among HIV-infected FPDs through the use of generic antiretroviral drugs in rural clinical settings. The effective reduction of AIDS mortality could be realized through increased coverage of therapy.

[An ambispective cohort study of the natural history of HIV infection among former unsafe commercial blood and plasma donors].

OBJECTIVE: Discussing the natural history and the influencing factors of HIV infection among former commercial blood and plasma donors engaged in unsafe blood donation practices in China. METHODS: Using ambispective cohort study, with data obtained from ten counties (districts) from six provinces in the National AIDS Control Demonstration Area. HIV/AIDS cases were found and confirmed prior to July 24, 2006 being former commercial blood. Plasma donors were selected and data regarding infection, incidence, death, and influencing factors was collected. Analysis was performed using SPSS 12.0 statistical analysis software. RESULTS: (1) In 7551 cases of HIV infection, there were 6533 typical progressors (86.52%, 4757 cases of AIDS), 108 rapid progressors (1.43%), 910 long-term non-progressors (12.05%) with 4865 cases progressed to AIDS (64.43%). The median incubation period for HIV progression to AIDS was nine years (95% CI:8.96-9.04). (2) According to data, from a total of 1157 AIDS cases without ARV therapy (23.78% of total AIDS cases), there were 283 confirmed AIDS-related deaths, of which the median survival time was 6 months (95% CI:4-7) and the two and three year fatality rates were 95% and 99%, respectively. (3) The duration of HIV incubation period was irrespective to gender and age at the time of HIV infection (P > 0.05). Length of survival for untreated AIDS showed correlation to gender (P < 0.05) but no correlation with culture, marital status or age at the time of diagnosis of AIDS (P > 0.05). CONCLUSION: Compared with the UNAIDS theory regarding slow disease progressors among adults, our study showed a longer AIDS incubation period and shorter outlook for untreated survival, but a similar incubation period for other routes of HIV infection.