Very high baseline HIV viremia impairs efficacy of non-nucleoside reverse transcriptase inhibitor-based ART: a long-term observation in treatment-naïve patients.

BACKGROUND: It is not completely clear whether a very high pre-therapy viral load (≥ 500 000 copies/ml) can impair the virological response. The aim of this study was to examine the influence of very high baseline HIV-RNA levels on long-term virological responses under one type of regimen. METHODS: A retrospective study was performed based on data from two multicenter cohorts in China from January to November 2009, and from May 2013 to December 2015. Untreated HIV infected adults between 18 and 65 years old were recruited before receiving non-nucleoside reverse transcriptase inhibitor-based regimen. All patients had baseline HIV-RNA levels over 500 copies/ml, good adherence, and were followed for at least 24 weeks. Virological suppression was defined as the first HIV-RNA < 50 copies/ml. Virological failure was defined as any of incomplete viral suppression (HIV-RNA ≥ 200 copies/ml without virological suppression within 24 weeks of treatment) and viral rebound (confirmed HIV-RNA level ≥ 50 copies/ml after virological suppression). Chi-square test, Kaplan-Meier analysis, Cox proportional hazards model and Logistic regression were used to compare virological response between each pretreated viral load stratum. RESULTS: A total of 758 treatment-naïve HIV patients in China were enlisted. Median follow-up time (IQR) was 144 (108-276) weeks. By week 48, rates of virological suppression in three groups (< 100 000, 100 000-500 000 and ≥ 500 000 copies/ml) were 94.1, 85.0, and 63.8%, respectively (P < 0.001). Very high baseline HIV viremia over 500 000 copies/ml were found to be associated with delayed virological suppression (≥ 500 000 vs <  100 000, adjusted relative hazard = 0.455, 95% CI: 0.32-0.65; P < 0.001) as well as incomplete viral suppression (≥ 500 000 vs < 100 000, adjusted odds ratio [aOR] = 6.084, 95% CI: 2.761-13.407; P < 0.001) and viral rebound (≥ 50 000 vs < 100 000, aOR = 3.671, 95% CI: 1.009-13.355, P = 0.048). CONCLUSIONS: Very high levels of pre-treatment HIV-RNA were related with delayed efficacy of NNRTI-based ART and increased risk of treatment failure. More potent initial regimens should be considered for those with this clinical character.

The effects of antiretroviral therapy initiation time on HIV reservoir size in Chinese chronically HIV infected patients: a prospective, multi-site cohort study.

BACKGROUND: The effect of ART initiation time on HIV-1 DNA reservoir in chronically infected individuals is not well understood. Determining the potential influencing factors associated with a low HIV-1 DNA level in chronic infection is an important step toward drug-free control. METHODS: A prospective study included 444 chronically HIV-infected adults was performed. Participants were divided into two groups: early initiation group (EIG) or delayed initiation group (DIG) based on their baseline CD4 count; 350 to 500 and < 350 cells/mm3, respectively. Total HIV-1 DNA was measured by quantitative PCR. Using the Mann-Whitney U test, the HIV-1 DNA level at week 48 was compared between the two groups. The influencing factors of the HIV-1 DNA and factors associated with achieving a low HIV-1 level at week 48 were analyzed. RESULTS: The HIV-1 DNA at week 48 in EIG was significantly lower than in DIG [2.12 (1.80-2.51) vs 2.58 (2.21-2.87) log10 copies/106peripheral blood mononuclear cells (PBMCs); p = 0.001]. Early ART initiation was positively associated with lower HIV-1 DNA at week 48 (p = 0.025). Similarly, baseline HIV-1DNA (p = 0.001) was positively associated with HIV-1DNA at week 48 and baseline CD4/CD8 ratio (p = 0.001) was inversely associated with HIV-1DNA at week 48. Early ART initiation (p = 0.003) and baseline HIV-1 DNA level (p < 0.001) were positively associated with achieving HIV-1 DNA < 100 copies/106 PBMCs at week 48. CONCLUSION: Early ART initiation is positively associated with a smaller size of viral reservoir and a higher possibility of achieving a low HIV-1DNA level at week 48 in Chinese chronically HIV-1 infected adult. TRIAL REGISTRATION: NCT01844297 ; Registered 1 May, 2013.

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.

Two-year prospective cohort study on quality of life outcomes among people living with HIV after initiation of antiretroviral therapy in Guangxi, China.

The long-term impact of antiretroviral therapy (ART) on quality of life (QOL) is not well understood in China. From 2007-2008, 332 treatment-naïve, HIV-infected adults from five hospitals in Guangxi were enrolled in a 2-year prospective cohort study. Information was collected at the time of ART initiation and during 6-, 12-, and 24-month follow-up visits. Significant improvements were observed across all QOL domains during the first 6 months on ART as measured using the WHOQOL-HIV BREF instrument. These were closely tracked by increases in CD4+ T cell counts, total lymphocyte counts, and the Karnofsky performance scores (p < .05). After 6 months, improvements were smaller and uneven across QOL domains; social relationships was the only domain to not significantly improve at 24 months compared to baseline. Poorer and socially isolated participants had lower QOL outcomes. Strengthening ART program interventions to increase social support for patients may increase QOL outcomes.

[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.

Common reservoirs for Penicillium marneffei infection in humans and rodents, China.

Human penicilliosis marneffei is an emerging infectious disease caused by the fungus Penicillium marneffei. High prevalence of infection among bamboo rats of the genera Rhizomys and Cannomys suggest that these rodents are a key facet of the P. marneffei life cycle. We trapped bamboo rats during June 2004-July 2005 across Guangxi Province, China, and demonstrated 100% prevalence of infection. Multilocus genotypes show that P. marneffei isolates from humans are similar to those infecting rats and are in some cases identical. Comparison of our dataset with genotypes recovered from sites across Southeast Asia shows that the overriding component of genetic structure in P. marneffei is spatial, with humans containing a greater diversity of genotypes than rodents. Humans and bamboo rats are sampling an as-yet undiscovered common reservoir of infection, or bamboo rats are a vector for human infections by acting as amplifiers of infectious dispersal stages.

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.