Impact of low-level viremia with drug resistance on CD4 cell counts among people living with HIV on antiretroviral treatment in China.

BACKGROUND: Maintaining plasma HIV RNA suppression below the limit of quantification is the goal of antiretroviral therapy (ART). When viral loads (VL) remain in low-level viremia (LLV), or between 201 and 999 copies/mL, the clinical consequences are still not clear. We investigated the occurrence of LLV with drug resistance and its effect on CD4 cell counts in a large Chinese cohort. METHODS: We analysed data of 6,530 ART-experienced patients (42.1 ± 10.9 years; 37.3% female) from the China's national HIV drug resistance (HIVDR) surveillance database. Participants were followed up for 32.9 (IQR 16.7-50.5) months. LLV was defined as the occurrence of at least one viral load (VL) measurement of 50-200 copies/mL during ART. Outcomes were drug resistance associated mutations (DRAM) and CD4 cell counts levels. RESULTS: Among 6530 patients, 58.0% patients achieved VL less than 50 copies/mL, 27.8% with VL between 50 and 999 copies/mL (8.6% experienced LLV), and 14.2% had a VL ≥ 1000 copies/mL. Of 1818 patients with VL 50-999 copies/mL, 182 (10.0%) experienced HIVDR, the most common DRAM were M184I/V 28.6%, K103N 19.2%, and V181C/I/V 10.4% (multidrug resistance: 27.5%), and patients with HIVDR had a higher risk of CD4 cell counts < 200 cells/µL (AOR 3.8, 95% CI 2.6-5.5, p < 0.01) comparing with those without HIVDR. Of 925 patients with VL ≥ 1000 copies/mL, 495 (53.5%) acquired HIVDR, the most common DRAM were K103N 43.8%, M184I/V 43.2%, M41L 19.0%, D67N/G 16.4%, V181C/I/V 14.5%, G190A/S 13.9% and K101E 13.7% (multidrug resistance: 75.8%), and patients with HIVDR had a higher risk of CD4 cell counts < 200 cells/µL (AOR 5.8, 95% CI 4.6-7.4, p < 0.01) comparing with those without HIVDR. CONCLUSION: Persistent with VL 50-999 copies/mL on ART is associated with emerging DRAM for all drug classes, and patients in this setting were at increased risk of CD4 cell counts < 200 cells/µL, which suggest resistance monitoring and ART optimization be earlier considered.

HIV drug resistance in patients in China's national HIV treatment programme who have been on first-line ART for at least 9 months.

BACKGROUND: The aim of this study was to assess trends in drug resistance and associated clinical and programmatic factors at a national level during the rapid scale up of ART. METHODS: Logistic regression was used to identify the factors associated with HIVDR. Variables associated with drug resistance in multivariable logistic regression were included in the Cochran-Armitage test for trend. RESULTS: A total of 11,976 patients were enrolled in the study. The prevalence of HIVDR among patients who received ART for 9-24 months during 2003-2008, 2009-2012, and 2013-2015 significantly decreased (15.5%, 6.3%, and 2.3%, respectively, P < 0.01). With respect to the class of antiretroviral, there were substantial increases in resistance to both non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) (2003-2008, 2009-2012, and 2013-2015: 49.7%, 58.9%, and 73.0%, respectively, P < 0.01). The prevalence of DR to protease inhibitors (PIs) was low, which supported their continued use as second-line therapy in China. CONCLUSIONS: Our results provide evidence for the effectiveness of China's "Treat All" approach to guide policy makers to improve training for healthcare providers and education on ART adherence among patients.

Blood pressure and noncommunicable diseases in middle-aged and older adults in China.

BACKGROUND: There are few studies examining the association between blood pressure (BP) and noncommunicable diseases (NCDs) in consideration of the new hypertension guidelines in China. METHODS: Data were drawn from the China Health and Retirement Longitudinal Study. 14 390 eligible participants (aged 45 years and older) were selected through four-stage, stratified, and cluster sampling. Hypertension was considered as a mean systolic blood pressure (SBP) of 130 mm Hg (old definition: 140 mm Hg) or higher, a mean diastolic blood pressure (DBP) of 80 mm Hg (old definition: 90 mm Hg) or higher or taking anti-hypertensive medication. Cochran-Armitage trend test and logistic regression analyses were conducted to test the association between BP level and NCDs. RESULTS: The prevalence of hypertension based on the latest definition was 56.35% (while by old definition: 42.75%). The awareness, treatment, and control among hypertensive participants were 38.62% (51.18%), 43.10% (56.81%), and 9.91% (13.06%), respectively. An increasing rate of NCDs (diabetes, heart disease, stroke, and memory-related disease) among participants were found with the ascending of BP level. After adjusted for demographics and behavioral risks, the following 3 NCDs had been shown to correlate with hypertension: diabetes (adjusted OR 1.15, 0.91-1.45 for elevated BP; 1.20, 0.97-1.49 for hypertension stage 1; 1.55, 1.28-1.86 hypertension stage 2), heart disease (0.94, 0.79-1.12; 1.05, 0.90-1.22; 1.28, 1.12-1.47), and stroke (1.77, 1.25-2.51; 1.32, 0.93-1.87; 1.85, 1.37-2.49). CONCLUSIONS: The association between hypertension and the risk of NCDs is of concern in China. The combined efforts on NCDs prevention and lowered blood pressure should be made by nationally integrated strategies, especially in middle-aged and older adults.

Hypertension and physical activity in middle-aged and older adults in China.

There are few studies examining the association between levels of physical activity and hypertension in middle-aged and older adults in China. Data were drawn from the Chinese Health and Retirement Longitudinal Study (using four-stage stratified probability-proportional-to-size sampling), involving 7113 individuals aged 45 years and older from 28 provinces of China. Hypertension was defined as a systolic BP ≥ 130 mm Hg, or diastolic BP ≥ 80 mm Hg, or self-reported use of anti-hypertensive medications. The awareness, treatment, and control among hypertensive participants were 53.12%, 43.37%, and 10.03%, respectively. The prevalence of hypertension was 56.12% among all the participants, higher in main city zones (58.68%) than villages (55.52%) and other areas (55.78%, p < 0.0001). Participants who were overweight (BMI ≥ 24: AOR 4.08, 95% CI 3.21-5.20, P < 0.0001; BMI ≥ 28: 10.03, 7.56-13.31, P < 0.0001), and drinking more than once a month (1.28, 1.12-1.46, P < 0.0001) were more likely to have hypertension. The decision tree model was established to analyze the importance of different levels of physical activity on hypertension prevention. Participants who usually participated in moderate-to-vigorous activity for more than 10 minutes (vigorous: 0.82, 0.73-0.91, P = 0.0004; moderate: 0.83, 0.75-0.92, P = 0.0006) were less likely to have hypertension. The results of the decision tree showed that the vigorous physical activity seemed to be more important than moderate and light activity to induce beneficial effects on prevention of hypertension. The strength of our study is in using the decision tree to clearly rank the importance of those key factors affecting hypertension.

Early antiretroviral therapy on reducing HIV transmission in China: strengths, weaknesses and next focus of the program.

Early antiretroviral therapy (ART) initiation is a recommended public health approach for the prevention of HIV-1 transmission. In this cohort study, we included 13132 serodiscordant couples. ART was initiated for patients with CD4+ T cell counts less than 200 cells/uL, 350 cells/uL, and 500 cells/uL respectively. This divided the ART treated couples into three groups. Univariate and multivariate intention-to-treat analyses were performed to examine the association between the study groups. Early-ART initiation was associated with a 45% lower risk of partner infection than was late-ART initiation (AHR 0.55, 95% CI, 0.37-0.81). Mid-ART initiation was associated with a 39% lower risk of partner infection than was late-ART initiation (AHR 0.61, 95% CI, 0.48-0.78). However, the risk reduction between the early and mid-ART groups was not significant. Drug compliance (AHR 1.55, 95% CI 1.03-2.35) and increased baseline viral load (AHR 1.41, 95% CI 1.33-1.51) were associated with an increased risk of infections among partners in the treatment. Prevention of HIV transmission as a result of early ART initiation was feasible on national and regional scales; however, many factors, such as the motivation to commence ART, adherence, and attrition, may affect the impact of this strategy in programmatic settings.

Adherence, virological outcome, and drug resistance in Chinese HIV patients receiving first-line antiretroviral therapy from 2011 to 2015.

Stavudine (D4T), zidovudine (AZT), and tenofovir (TDF) along with lamivudine (3TC) are the most widely used HIV treatment regimens in China. China's National Free Antiretroviral Treatment Programme (NFATP) has replaced D4T with AZT or TDF in the standard first-line regimens since 2010. Few studies have evaluated the adherence, virological outcome, and drug resistance in HIV patients receiving first-line antiretroviral therapy (ART) from 2011 to 2015 due to changes in ART regimen.From 2011 to 2015, 2787 HIV patients were examined, with 364, 1453, and 970 patients having initiated D4T-, AZT-, and TDF-based first-line ART regimens, respectively. The Cochran-Armitage test was used to examine the trends in clinical and virological outcomes during 2011 to 2015. Logistic regression was used to examine the effects of different regimens after 9 to 24 months of ART.From 2011 to 2014-2015, adverse drug reactions decreased from 18.9% to 6.7%, missed doses decreased from 9.9% to 4.6%, virological failure decreased from 16.2% to 6.4%, and drug resistance rates also significantly decreased from 5.4% to 1.1%. These successes were strongly associated with the standardized use of TDF- or AZT-based regimens in place of the D4T-based regimen. Poor adherence decreased from 11.3% in patients who initiated D4T-based regimens to 4.9% in those who initiated TDF-based regimens, adverse drug reactions decreased from 32.4% to 6.7%, virological failure reduced from 18.7% to 8.6%, and drug resistance reduced from 5.8% to 2.9%. Compared with patients who initiated AZT-based regimens, patients who initiated TDF-based regiments showed significant reductions in adherence issues, adverse drug reactions, virological outcomes, and drug resistance. Significant differences were also observed between those who initiated D4T- and AZT-based regimens.The good control of HIV replication and drug resistance was attributed to the success of China's NFATP from 2011 to 2015. This study provided real world evidence for further scaling up ART and minimizing the emergence of drug resistance in the "Three 90" era.

Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China.

BACKGROUND: HIV drug resistance is associated with faster clinical progression of AIDS. However, the effect of significant polymorphisms and mutational covariation on mortality among HIV/AIDS patients receiving long-term antiretroviral therapy (ART), have rarely been studied. METHODS: In this prospective cohort study from December 2003 to December 2014, we present a new computational modelling approach based on bioinformatics-based models and several statistical methods to elucidate the molecular mechanisms involved in the acquisition of polymorphisms and mutations on death in HIV/AIDS patients receiving long-term ART in China. RESULTS: This study involved 654 ART-treated patients, who had been followed for 5473.4 person-years, a median of 9.8 years, and 178 died (25.2%, 3.3/100 person-years). The first regimens included AZT/d4T + NVP+ ddI (78.9%) or AZT/d4T + NVP+ 3TC (20.0%). We calculated an individual Ka/Ks value for each specific amino acid mutation. Result showed that 20 polymorphisms (E6D, Q18H, E35D, S37N, T39A, K43E, S68N, L74I, I93L, K103N, V106A, E169D, Y181C, G190A, Q197K, T200V, T200E, T215I, E224D and P225H) were strongly associated with AIDS related deaths. Among them, 7 polymorphisms (L74I, K103N, V106A, Y181C, G190A, T215I and P225H) were known to be drug resistance mutations, 7 polymorphisms (E6D, E35D, S37N, I93L, E169D, T200V and T200E were considered to be potential drug resistance mutations, and 6 polymorphisms (T39A, K43E, S68N, Q197K, T200V and E224D) were newly found to have an association with drug resistance mutations, which formed a complex network of relationships. CONCLUSIONS: Some polymorphisms and mutational covariation may be the important influencing factors in the failure of treatment. Understanding these mechanisms is essential for the development of new therapies, designing optimal drug combinations, and determining effective clinical management of individual patients.