Background: The Public Health Agency of Canada reviewed sexual transmission of HIV between serodiscordant partners to support examination of the criminal justice system response to HIV nondisclosure by the Department of Justice of Canada. We sought to determine HIV transmission risk when an HIV-positive partner takes antiretroviral therapy, has a suppressed viral load or uses condoms. Methods: We conducted an overview and systematic review update by searching MEDLINE and other databases (Jan. 1, 2007, to Mar. 13, 2017; and Nov. 1, 2012, to Apr. 27, 2017, respectively). We considered reviews and studies about absolute risk of sexual transmission of HIV between serodiscordant partners to be eligible for inclusion. We used A Measurement Tool to Assess Systematic Reviews (AMSTAR) for review quality, Quality in Prognosis Studies (QUIPS) instrument for study risk of bias and then the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence across studies. We calculated HIV incidence per 100 person-years with 95% confidence intervals (CIs). We assigned risk categories according to potential for and evidence of HIV transmission. Results: We identified 12 reviews. We selected 1 review to estimate risk of HIV transmission for condom use without antiretroviral therapy (1.14 transmissions/100 person-years, 95% CI 0.56–2.04; low risk). We identified 11 studies with 23 transmissions over 10 511 person-years with antiretroviral therapy (0.22 transmissions/ 100 person-years, 95% CI 0.14–0.33; low risk). We found no transmissions with antiretroviral therapy and a viral load of less than 200 copies/mL across consecutive measurements 4 to 6 months apart (0.00 transmissions/100 person-years, 95% CI 0.00–0.28; negligible risk regardless of condom use). Interpretation: Based on high-quality evidence, there is a negligible risk of sexual transmission of HIV when an HIV-positive sex partner adheres to antiretroviral therapy and maintains a suppressed viral load of less than 200 copies/mL measured every 4 to 6 months. Sexual transmissions of HIV have occurred when viral load was more than 200 copies/mL with antiretroviral therapy or condoms alone were used, although the risk remains low. These findings will help to support patient and clinician decision-making, affect public health case management and contact tracing, and inform justice system responses to HIV nondisclosure.

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Risk of sexual transmission of human immunodeficiency virus with antiretroviral therapy, suppressed viral load and condom use: a systematic review

Specific Reactivation of Latent HIV-1 by dCas9-SunTag-VP64-mediated Guide RNA Targeting the HIV-1 Promoter

The introduction of the National Free Antiretroviral Therapy Program (NFATP) in 2003 by the China National Center for AIDS/STD Control and Prevention has led to dramatic increases in antiretroviral therapy (ART) coverage among HIV-infected Chinese patients. Despite limitations in the number of available free antiretroviral drugs, the overall mortality associated with HIV/AIDS has dropped from 39.3 per 100 person-years in 2002 to 3.1 in 2014. In this review, we summarize the challenges, responses, and achievements of antiretroviral therapy (ART) in China over the past 20 years. Continuous optimization of the Chinese National Guidelines for HIV/AIDS Diagnosis and Treatment has been guided by data from serial domestic multi-center studies aimed at evaluating efficacy and toxicity of available ART regimens among Chinese patients with HIV, with the goal of maximizing adherence, access, and efficacy. In addition, increasing attention has been focused on the importance of continuity in the HIV care cascade to promote linkage to care, and address the multidisciplinary chronic care needs HIV/AIDS patients on lifelong ART. Great progress has been achieved in the past 20 years in terms of access to and optimization of antiretroviral treatment in China. As the number of patients receiving long-term ART continues to grow, the focus of HIV/AIDS treatment has gradually transitioned from urgent care to the management of non-AIDS-related chronic complications and control of chronic inflammation.

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Optimizing Treatment for Adults with HIV/AIDS in China: Successes over Two Decades and Remaining Challenges.

Background 
Many HIV-infected patients demonstrate disability and lower aerobic capacity. The inclusion of resistance training combined with aerobic exercise in a single program is known as combined aerobic and resistance exercise (CARE) and seems to be an effective strategy to improve muscle weakness, as well as aerobic capacity in HIV-infected patients. We performed a meta-analysis to investigate the effects of CARE in HIV-infected patients.


Methods 
We searched MEDLINE, Cochrane Controlled Trials Register, EMBASE, CINAHL (from the earliest date available to august 2014) for controlled trials that evaluated the effects of CARE in HIV-infected patients. Weighted mean differences (WMD) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I2 test.


Results 
Seven studies met the study criteria. CARE resulted in improvement in Peak VO2 WMD (4.48 mL·kg-1·min-1 95% CI: 2.95 to 6.0), muscle strength of the knee extensors WMD (25.06 Kg 95% CI: 10.46 to 39.66) and elbow flexors WMD (4.44 Kg 95% CI: 1.22 to 7.67) compared with no exercise group. The meta-analyses also showed significant improvement in Health status, Energy/Vitality and physical function domains of quality of life for participants in the CARE group compared with no exercise group. A nonsignificant improvement in social function domain of quality of life was found for participants in the CARE group compared with no exercise group.


Conclusions 
Combined aerobic and resistance exercise may improve peak VO2, muscle strength and health status, energy and physical function domains of quality of life and should be considered as a component of care of HIV-infected individuals.

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Effects of Combined Aerobic and Resistance Exercise on Exercise Capacity, Muscle Strength and Quality of Life in HIV-Infected Patients: A Systematic Review and Meta-Analysis.

To estimate the nationwide and regional distribution of HIV-1 genotypes in China in the past three decades, province-specific HIV-1 molecular epidemiology data were derived from 260 independent studies of HIV molecular prevalence through searching PubMed, VIP Chinese Journal Database (VIP), China National Knowledge Infrastructure, and Wanfang Data from January 1981 to December 2015. The nationwide and regional distribution of HIV-1 genotypes was estimated by weighting the genotype distribution from each province- and risk-specific subpopulation with the number of reported cases in the corresponding subgroups in the relevant periods. A sharp transition of HIV-1 subtypes and recombinant distribution was observed in various risk groups and regions over time. CRF01_AE has rapidly surged among almost all risk groups and in all areas, and it has become dominant among men who have sex with men and heterosexuals. A wide variety of new circulating recombinant forms (CRFs) and unique recombinant forms (URF...

Nationwide Trends in Molecular Epidemiology of HIV-1 in China

Highly active antiretroviral therapy (HAART) has led to a dramatic decrease in AIDS-related morbidity and mortality [1, 2] through sustained suppression of human immunodeficiency virus (HIV) replication [3] and reconstitution of the immune response [4]. However, the eventual development of HIV drug resistance (DR) over time is largely inevitable at the population level, and HIV DR is one of the strongest predictors of treatment failure [5, 6]. It can render existing therapies ineffective [7–9], increasing the risk of viral rebound and opportunistic infections. Second-line drugs provide alternative therapeutic options to suppress resistant strains, but their high cost and limited availability in some areas make them a less viable option. As HIV DR prevalence increases at the population level, the secondary transmission of transmitted DR is also a major public health concern [10]. A better understanding of long-term HIV DR rates and emergence of drug-resistant mutations after HAART initiation will be crucial to the effective therapeutic and preventive use of HAART.

China's National Free Antiretroviral Treatment Program (NFATP) is now a decade old [11], having begun as a pilot program with just 100 enrollees in a rural region where most patients were infected through former plasma donation in the early 1990s [11, 12]. The program today is notable in terms of both scale and impact. As of 31 December 2009, a cumulative total of 82 540 patients received HAART through the program, during which time the HIV/AIDS-related mortality rate fell from 39.3 to 14.2 deaths per 100 person-years [13].

Owing to its early rapid scale-up, as well as evolving recommendations for treatment eligibility—in 2008 China's HAART initiation threshold increased from 200 to 350 CD4 cells/µL [14]—expansion of HAART access in China outpaced program development in the early stages. Routine laboratory screening is only available at a small portion of the >3700 HAART delivery sites across the county; between 2005 and 2008, only 30% of patients had received ≥1 viral load test a year [15]. Specialized training in AIDS care for local providers is also limited, and in rural areas many AIDS care physicians lack a formal medical education [16]. These factors, along with the limited drug regimen choice in the early years of the program, have all contributed to the emergence of HIV DR in the Chinese HAART population. Observational studies have shown that the prevalence of drug-resistant strains among treated HIV/AIDS patients in China ranges from 2.38% to 54.67% [17, 18] after 1 year of HAART. However, it is difficult to draw broader conclusions owing to the heterogeneity of study populations and sampling methods. Because few studies have traced trends of HIV DR emergence during longer durations of HAART exposure, the objective of this investigation was to conduct a systematic review and meta-analysis and generate pooled estimates of the emerging trends of HIV DR after first-line HAART initiation in Chinese patients with HIV/AIDS.

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Emerging trends of HIV drug resistance in Chinese HIV-infected patients receiving first-line highly active antiretroviral therapy: a systematic review and meta-analysis

The aim of this paper was to review cohort studies that analyze changes in the quality of life of people living with HIV/AIDS. We searched the PubMed and EmBase databases from inception to December 2012 for primary cohort studies of the quality of life of people living with HIV/AIDS after combination antiretroviral therapy (cART). Two independent reviewers screened and selected published studies of quality of life that had been followed up for more than 12 weeks after the beginning of cART. Data from the papers were analyzed to identify common characteristics of the effects of cART on the quality of life of HIV/AIDS patients. Eight cohort studies were found: only four were assessed as high quality and four were assessed as moderate quality. None of the studies described patient selection. Six studies followed the patients for one year or more, and the other studies for less than 6 months. Seven studies reported quality of life had been improved after initiation of cART, and one study reported no change. Previous research suggested that cART improved the quality of life of AIDS patients for a limited time, so further research for longer periods is needed to confirm this outcome.

A systematic review of cohort studies of the quality of life in HIV/AIDS patients after antiretroviral therapy.

BACKGROUND: Consistent and correct condom use and suppressive antiretroviral therapy for the infected partner are two of the primary strategies recommended for prevention of heterosexual HIV transmission in serodiscordant couples today. The applied effectiveness of treatment as a prevention strategy in China is still under investigation and much less is known about its effects in the presence of other prevention strategies such as consistent condom use. METHODS: We conducted a systematic search in PubMed and three Chinese language databases to identify relevant articles for the estimation of relative effectiveness of a) consistent condom use and b) ART use by index partners for preventing HIV transmission in serodiscordant couples. We also estimated the prevention effectiveness of ART stratified by condom use level and the prevention effectiveness of consistent condom use stratified by ART use level. RESULTS: Pooled results from the eleven eligible studies found a pooled HIV seroconversion incidence of 0.92 cases per 100 person years (PY) among HIV-negative spouses whose index partners were taking ART versus 2.45 cases per 100 PY in untreated couples. The IRR comparing seroconversion in couples where the index-partner was on ART versus not on ART was 0.47 (95%CI: 0.43 0.52) while stratified by condom use the IRR was 0.33(0.170.64). The IRR comparing incidence in couples reporting "consistent condom use" versus those reporting otherwise was 0.02(95%CI:0.010.04) after stratified by ART use level the IRR was 0.01(95%CI: 0.00 0.06). CONCLUSIONS: ART use by index partners could reduce HIV transmission in serodiscordant couples and the effectiveness of this prevention strategy could be further increased with consistent condom use.

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Effectiveness of ART and Condom Use for Prevention of Sexual HIV Transmission in Serodiscordant Couples: A Systematic Review and Meta-Analysis

Objective To provide information on the geographical distribution of HIV-1 genotypes and subtypes in the population of China. Methods A comprehensive search was carried out in China Hospital Knowledge Database（CHKD）,Wanfang（Chinese）,CBMDisc and PubMed databases to identify all studies published related to HIV-1 genotypes in China. All studies were grouped according to the sites,period and objects for analyzing the distribution of HIV genotypes. Results A total of 175 studies were included in this Meta-analysis,which contained 285 records. We found that the predominate genotypes in China were B’ subtype,CRF01_AE,CRF07_BC and CRF08_BC,but the subtype distribution of HIV-1 was different in the western and southern parts of the country. CRF01_AE had a significant increase while subtype B’ showed a decrease. There were various HIV-1 subtypes among individuals who acquired HIV through sexual contacts and CRF01_AE was most commonly identified in this group of people. Conclusion The distribution of HIV-1 genotypes in Chinese people significantly changed,together with high complexity of the HIV-1 epidemics noticed in China.

Key words: 
HIV- 1 ;  Genotype;  Systematic review

[Distribution of HIV-1 genotypes in China: a systematic review].

Since 2012, several human immunodeficiency virus (HIV) treatment guidelines have begun calling for immediate treatment of all HIV-infected persons regardless of CD4 cell count [1–3]. The guideline changes are attributable, in part, to results of a clinical trial showing that antiretroviral treatment (ART) can stop sexual HIV transmission [4], as well as evidence that earlier ART reduces HIV morbidity and mortality [5].

Supporters of rapid rollout of “treatment as prevention” strategies argue that the effect is already visible in areas where broader ART access has coincided with declines in measured sexual transmission of HIV [6, 7]. However exceptions to this pattern [8] and the potential risks of rapid rollout such as widespread emergence of drug resistance [9] or changes in risk behaviors [10], have tempered enthusiasm. In resource-poor settings, limited access to the resources required for durable viral suppression—optimal drug regimens and routine laboratory monitoring, for example—have prompted calls for research to inform treatment as prevention guidelines adapted to these locations [11].

Of about a dozen observational studies reporting on the real world effect of ART on sexual HIV transmission by following serodiscordant couples, in which only 1 partner is infected [12, 13], only 3 have followed those receiving routine care in resource-limited settings (the remainder tracked patients in wealthy countries or who received specialized care as part of scientific research studies). One of these 3 studies reported that ART prevented linked HIV transmission in couples from the southern Chinese province of Yunnan, though the uniqueness of the cohort—the initially infected (or “index”) partners were overwhelming male (78.7%), with about half reporting historic drug use (45.1%)—and high loss of follow-up among untreated couples, limited generalizability of the results [13]. Notably, the remaining 2 reports from Uganda [14] and Henan Province in China [15], both reported a lack of protective immunity attributable to the index partner's ART use. Follow-up of the Henan cohort has been ongoing, and an analysis of a later phase of follow-up showed that ART was instead highly protective against transmission [16], raising further questions about the relationship between ART exposure and HIV transmission in nontrial settings.

The Chinese government provides free HIV testing and universal ART through the existing healthcare system, in many cases managed by nonphysician clinicians [17], which provides a realistic version of proposed test and treat strategies [18]. The purpose of the current report is to investigate how well ART can work under such conditions so as to inform future programming for the use of treatment as prevention, particularly in resource poor settings.

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Lin Zhu

Papers

Emerging trends of HIV drug resistance in Chinese HIV-infected patients receiving first-line highly active antiretroviral therapy: a systematic review and meta-analysis

A systematic review of cohort studies of the quality of life in HIV/AIDS patients after antiretroviral therapy.

Effectiveness of ART and Condom Use for Prevention of Sexual HIV Transmission in Serodiscordant Couples: A Systematic Review and Meta-Analysis

[Distribution of HIV-1 genotypes in China: a systematic review].

Treatment to Prevent HIV Transmission in Serodiscordant Couples in Henan, China, 2006 to 2012