Kathrine Meyers

High interest in a long-acting injectable formulation of pre-exposure prophylaxis for HIV in young men who have sex with men in NYC: a P18 cohort substudy.

Objective In the context of continued high rates of condomless anal intercourse and HIV-1 infection, young men who have sex with men (YMSM) need additional effective and desirable HIV prevention tools. This study reports on the willingness of a racially-ethnically diverse cohort of YMSM to use a new biomedical prevention approach, a long-acting injectable pre-exposure prophylaxis (LAI-PrEP) agent. Methods A cross-sectional study conducted between June-August 2013 recruited participants from an ongoing cohort study of YMSM in NYC. Participants included 197 YMSM, of whom 72.6% (n = 143) identified as men of color. Two outcomes were measured through computer-assisted self-interviews: 1) willingness to use long-acting injectable PrEP and 2) preference for route of administration of PrEP. In addition, concerns about perceived impacts of PrEP on health and risk behavior, access to health services, and stigma were investigated. Results Over 80% (n = 159/197, p<0.001) of participants stated they would be willing to use LAI-PrEP. With regards to preference for mode of delivery 79.2% (n = 156/197, p<0.001) stated they would prefer an injection administered every three months over a daily pill or neither one. Conclusions This study is the first to explore acceptability of LAI-PrEP in the US. A significant majority of participants expressed willingness to use LAI and the majority preferred LAI-PrEP. LAI-PrEP holds great promise in that it could circumvent the adherence challenges associated with daily dosing, especially if nested within appropriate psycho-behavioral support. Medical providers whose patients include YMSM at high risk for HIV infection should note the positive attitudes toward PrEP, and specifically LAI-PrEP.

A Case Series of 104 Women Infected with HIV-1 via Blood Transfusion Postnatally: High Rate of HIV-1 Transmission to Infants through Breast-Feeding

We investigated transmission of human immunodeficiency virus type 1 (HIV-1) via breast-feeding by 104 Chinese mothers who acquired the infection through blood transfusion postnatally. Of 106 children, 38 (35.8%) were infected. All children survived to age 5 years, and their survival curve was similar to that of their mothers. These findings suggest a high rate of HIV-1 transmission via breast-feeding when mothers were infected postnatally via blood transfusion, perhaps because of the higher viremia expected during the acute phase of infection. The course of disease among infected children was significantly less rapid than that among newborns infected perinatally, suggesting that a brief window of HIV-1-free life often enables the immune system of an infant to stave off rapid disease progression.

Prevention of mother-to-child transmission of HIV-1 using highly active antiretroviral therapy in rural Yunnan, China.

Objective:To demonstrate that the use of highly active antiretroviral therapy (HAART) to interrupt transmission of HIV-1 from mother to baby is effective, safe, and feasible in a remote rural region of China. Methods:Between November 2005 and May 2009, we enrolled 279 HIV-1-infected pregnant women to receive HAART to interrupt transmission of HIV-1 to their newborns across 16 counties in Yunnan. All women were started on triple combination therapy and submitted to regular blood draws to monitor CD4 T cells and viral load in their blood plasma. Infants received a single dose of nevirapine at birth and 1 or 4 weeks of zidovudine depending on the length of the mothers regimen. Exclusive formula feeding was recommended, and families were provided with 12-month supply of formula. Mothers and infant pairs were followed for 12-18 months postdelivery. Results:Of 279 enrolled HIV-infected women, 222 (79.6%) were identified and started treatment by 28 weeks of pregnancy. Viral load was undetectable at time of delivery for 62.4% (136 of 218) at delivery, with a mean 1.76 log viral load reduction between enrollment and delivery. Two of 193 babies (1.0%) who have already been tested became infected with HIV-1. Seven of 223 babies have died. By Kaplan-Meier analysis, cumulative one-year survival was 96.3%. Conclusions:The project demonstrated that HAART for all infected pregnant women is effective with a vertical transmission rate of ∼1%. Thus, this project provides a model for China to scale up its efforts to prevent mother-to-child transmission of HIV-1.

HIV burden in men who have sex with men: a prospective cohort study 2007–2012

We conducted a prospective cohort study among HIV-negative MSM aged 18 years or older between 2007 and 2012 in Beijing, China to measure the rates of incident HIV and identify risk factors for infection. Among 5,800 participants evaluated at enrollment, we identified 486 prevalent cases of HIV (8.4%). Among the 3,625 enrollees who were HIV-negative at enrollment and completed at least one follow-up interview, we identified 440 incident cases of HIV in the follow up period: this constituted an HIV incidence rate of 7.1 per 100 person-years (95% CI: 6.4–7.7). Early treatment of syphilis may have significantly reduced risk of HIV infection (RR: 1.45, 95% CI: 1.11–1.93), while MSM presenting perfect compliance in the cohort did not show reduction in HIV infection. Our study suggested that HIV incidence has been remained high in this sample of Chinese MSM during the intensive preventive intervention, suggesting that we need to find new strategies to prevent HIV infection in this population.

Planning ahead for implementation of long-acting HIV prevention: challenges and opportunities.

Purpose of review Broad-based access, uptake, and dissemination of daily oral HIV preexposure prophylaxis (PrEP) have been slow, despite strong evidence for efficacy. Effective and efficient implementation of long-acting HIV prevention products will require both analysis of the dynamics and determinants of daily oral PrEP implementation and identification of the distinct challenges and opportunities inherent in emerging technologies. Recent findings Evidence suggests the importance of addressing implementation issues at three levels: patient, provider, and system. Patient-level factors include targeted education and messaging, tailored supports to enhance acceptability and uptake, and effective strategies for promoting adherence/persistence and retention in care. Provider-level factors include engaging a broad mix of providers, while ensuring adequate training and support for patient assessment, counseling, and follow-up. Systems-level factors include optimal delivery modalities, resource allocation, and ensuring access to populations most in need of new prevention options. Summary Formative social/behavioral research must be undertaken proactively to prepare for and address future implementation challenges and reduce the gap between proving efficacy in clinical trials and assuring real-world effectiveness. Conceptualizing new HIV prevention technologies as behavioral interventions at the level of the patient, provider, and system will be paramount to effective and efficient implementation.

Predictors of elective pregnancy termination among women diagnosed with HIV during pregnancy in two regions of China, 2004–2010

Please cite this paper as: Liang K, Meyers K, Zeng W, Gui X. Predictors of elective pregnancy termination among women diagnosed with HIV during pregnancy in two regions of China, 2004–2010. BJOG 2013;120:1207–1214.

Cytokine cascade and networks among MSM HIV seroconverters: implications for early immunotherapy

The timing, intensity and duration of the cytokine cascade and reorganized interrelations in cytokine networks are not fully understood during acute HIV-1 infection (AHI). Using sequential plasma samples collected over three years post-infection in a cohort of MSM HIV-1 seroconvertors, we determined the early kinetics of cytokine levels during FiebigI-IV stages using Luminex-based multiplex assays. Cytokines were quantified and relationships between cytokines were assessed by Spearman correlation. Compared with HIV-negative MSM, HIV-infected individuals had significantly increased multiple plasma cytokines, including GM-CSF, IFN-α2, IL-12p70, IP-10 and VEGF, during both acute and chronic stages of infection. Furthermore, rapid disease progressors (RDPs) had earlier and more robust cytokine storms, compared with slow disease progressors (SDPs) (49.6 days vs. 74.9 days, respectively; 6.7-fold vs. 3.7-fold change of cytokines, respectively), suggesting the faster and stronger cytokine storm during AHI could promote disease progression. On the other hand, HIV-1 infection induced more interlocked cytokines network, establishing new strong correlations and imposing a higher rigidity. There were, respectively, 146 (44.9%) statistically significant correlations of cytokines in RDPs and 241 (74.2%) in SDPs (p < 0.001). This study suggests that immunomodulatory interventions aimed at controlling cytokine storm in AHI may be beneficial to slow eventual disease progression.

Extending access with long-acting antiretroviral therapy: the next advance in HIV-1 therapeutics and prevention.

DOI:10.1097/COH.0000000000000167 Approximately 20 years ago, the era of combination antiretroviral therapy (cART) was ushered in, made possible by the convergence of three pivotal discoveries: the understanding of the dynamic nature of HIV-1 replication in vivo that provided the scientific underpinning for the use of triple cART [1,2]; the identification and clinical development of novel agents that effectively and durably suppress viral replication [3–6]; and the discovery and availability of the viral load assay which allowed the rapid determination of drug efficacy and regimen durability [7]. Since then, 35 drugs in five classes (with four all-in-one combination tablets) have received approval for the treatment of HIV-1 infection. Over time, these regimens have become increasingly tolerable and convenient, and, when taken as prescribed, highly efficacious and durable. Clinical trials of cART routinely demonstrate regimen efficacy of 90% or higher, with virologic failure rates below 5% [8]. Furthermore, it has become clear that effective treatment of HIV-1 infection is overwhelmingly effective in preventing HIV-1 transmission among serodiscordant couples [9]. In recent years, orally administered antiretrovirals have entered the prevention field as chemoprophylaxis of HIV-1 infection [10–13]. Preexposure prophylaxis, or PrEP, has been shown to be extremely effective, reducing the risk of HIV-1 infection by up to 86% in the context of clinical trials [14,15], though effectiveness has been intimately linked to adherence to the prescribed regimen [16,17]. Despite these advances, the miracle of cART has yet to be experienced by all who need it, and the challenges of the current treatment paradigm, daily oral therapy, are great. In resource-rich and resource-limited settings, novel approaches to both treatment and prevention are needed – advances that are capable of overcoming current limitations such as nonadherence and treatment fatigue. The present edition of Current Opinions in HIV and AIDS features a comprehensive series of articles on the next additions to the treatment and

Burden of sleep disturbances and associated risk factors: A cross-sectional survey among HIV-infected persons on antiretroviral therapy across China

This study evaluated the prevalence and factors associated with sleep disturbance in a large cohort of HIV-infected patients across China. A cross-sectional study was conducted among HIV-infected patients on antiretroviral therapy at 20 AIDS clinics. The Pittsburgh Sleep Quality Index was self-administered by subjects. Socio-demographic characteristics, medical history and HIV-related clinical data were collected. 4103 patients had complete data for analysis. Sleep disturbances were observed in 43.1% of patients. Associated factors in multivariable analysis included psychological factors: anxiety (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.44–4.00; P < 0.001), depression (OR, 2.09; 95% CI, 1.70–2.57; P < 0.001), and both anxiety and depression (OR, 5.90; 95% CI, 4.86–7.16; P < 0.001); sociodemographic factors: MSM (OR, 1.26; 95% CI, 1.04–1.52; P = 0.018), being single (OR, 1.45; 95%CI 1.21–1.74; P < 0.001), higher education (OR, 1.25; 95% CI, 1.03–1.53; P = 0.025); and clinical factors: suboptimal adherence (OR,1.51; 95% CI,1.23–1.85; P < 0.001), regimen-switching (OR, 1.94; 95% CI, 1.12–3.35; P = 0.018), and antidepressant use (OR, 1.98; 95% CI, 1.47–2.67; P = 0.044). Prevalence of sleep disturbance is high in this large Chinese cohort. Associated factors appear related to psychological and social-demographic factors. Health workers may consider routinely assessing sleep disturbances among HIV-infected patients, especially in the first three months after HIV diagnosis, and referring for mental health services, which may positively impact adherence to treatment.

Early Initiation of ARV During Pregnancy to Move towards Virtual Elimination of Mother-to-Child-Transmission of HIV-1 in Yunnan China.

Objective To identify factors associated with mother-to-child-transmission and late access to prevention of maternal to child transmission (PMTCT) services among HIV-infected women; and risk factors for infant mortality among HIV-exposed infants in order to assess the feasibility of virtual elimination of vertical transmission and pediatric HIV in this setting. Design Observational study evaluating the impact of a provincial PMTCT program. Methods The intervention was implemented in 26 counties of Yunnan Province, China at municipal and tertiary health care settings. Log linear regression models with generalized estimating equations were used to identify unadjusted and adjusted correlates for late ARV intervention and MTCT. Cox proportional hazard models with robust sandwich estimation were applied to examine correlates of infant mortality. Results Mother-to-child- transmission rate of HIV was controlled to 2%, with late initiation of maternal ARV showing a strong association with vertical transmission and infant mortality. Risk factors for late initiation of maternal ARV were age, ethnicity, education, and having a husband not tested for HIV. Mortality rate among HIV-exposed infants was 2.9/100 person-years. In addition to late initiation of maternal ARV, ethnicity, low birth weight and preterm birth were associated with infant mortality. Conclusions This PMTCT program in Yunnan achieved low rates of MTCT. However the infant mortality rate in this cohort of HIV-exposed children was almost three times the provincial rate. Virtual elimination of MTCT of HIV is an achievable goal in China, but more attention needs to be paid to HIV-free survival.