HIV DNA Reservoir Increases Risk for Cognitive Disorders in cART-Na?ve Patients

Objectives

Cognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART). Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14⁺ enriched monocytes predicted cognitive impairment and brain injury.

Methods

We enrolled 61 cART-naïve HIV-infected Thais in a prospective study and measured HIV DNA in CD14⁺ enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS) to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF).

Results

The mean (SD) age was 35 (6.9) years, CD4 T-lymphocyte count was 236 (139) and log₁₀ plasma HIV RNA was 4.8 (0.73). Twenty-eight of 61 met HAND criteria. The log₁₀ CD14⁺ HIV DNA was associated with HAND in unadjusted and adjusted models (p = 0.001). There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number). Plasma CD14⁺ HIV DNA was associated with plasma and CSF neopterin (p = 0.023) and with MRS markers of neuronal injury (lower N-acetyl aspartate) and glial dysfunction (higher myoinositol) in multiple brain regions.

Interpretation

Reservoir burden of HIV DNA in monocyte-enriched (CD14⁺) peripheral blood cells increases risk for HAND in treatment-naïve HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS.     

Drug Users in Amsterdam: Are They Still at Risk for HIV?

Background and Aims

To examine whether drug users (DU) in the Amsterdam Cohort Study (ACS) are still at risk for HIV, we studied trends in HIV incidence and injecting and sexual risk behaviour from 1986 to 2011.

Methods

The ACS is an open, prospective cohort study on HIV. Calendar time trends in HIV incidence were modelled using Poisson regression. Trends in risk behaviour were modelled via generalized estimating equations. In 2010, a screening for STI (chlamydia, gonorrhoea and syphilis) was performed. Determinants of unprotected sex were studied using logistic regression analysis.

Results

The HIV incidence among 1298 participants of the ACS with a total follow-up of 12,921 person-years (PY) declined from 6.0/100 PY (95% confidence interval [CI] 3.2–11.1) in 1986 to less than 1/100 PY from 1997 onwards. Both injection and sexual risk behaviour declined significantly over time. Out of 197 participants screened for STI in 2010–2011, median age 49 years (IQR 43–59), only 5 (2.5%) were diagnosed with an STI. In multivariable analysis, having a steady partner (aOR 4.1, 95% CI 1.6–10.5) was associated with unprotected sex. HIV-infected participants were less likely to report unprotected sex (aOR 0.07, 95% CI 0.02–0.37).

Conclusions

HIV incidence and injection risk behaviour declined from 1986 onwards. STI prevalence is low; unprotected sex is associated with steady partners and is less common among HIV-infected participants. These findings indicate a low transmission risk of HIV and STI, which suggests that DU do not play a significant role in the current spread of HIV in Amsterdam.     

Is HIV Infection a Risk Factor for Multi-Drug Resistant Tuberculosis? A Systematic Review

Background

Tuberculosis (TB) is an important cause of human suffering and death. Human immunodeficiency virus (HIV), multi-drug resistant TB (MDR-TB), and extensive drug resistant tuberculosis (XDR-TB) have emerged as threats to TB control. The association between MDR-TB and HIV infection has not yet been fully investigated. We conducted a systematic review and meta-analysis to summarize the evidence on the association between HIV infection and MDR-TB.

Methods and Results

Original studies providing Mycobacterium tuberculosis resistance data stratified by HIV status were identified using MEDLINE and ISI Web of Science. Crude MDR-TB prevalence ratios were calculated and analyzed by type of TB (primary or acquired), region and study period. Heterogeneity across studies was assessed, and pooled prevalence ratios were generated if appropriate. No clear association was found between MDR-TB and HIV infection across time and geographic locations. MDR-TB prevalence ratios in the 32 eligible studies, comparing MDR-TB prevalence by HIV status, ranged from 0.21 to 41.45. Assessment by geographical region or study period did not reveal noticeable patterns. The summary prevalence ratios for acquired and primary MDR-TB were 1.17 (95% CI 0.86, 1.6) and 2.72 (95% CI 2.03, 3.66), respectively. Studies eligible for review were few considering the size of the epidemics. Most studies were not adjusted for confounders and the heterogeneity across studies precluded the calculation of a meaningful overall summary measure.

Conclusions

We could not demonstrate an overall association between MDR-TB and HIV or acquired MDR-TB and HIV, but our results suggest that HIV infection is associated with primary MDR-TB. Future well-designed studies and surveillance in all regions of the world are needed to better clarify the relationship between HIV infection and MDR-TB.     

Retinal Arterioles Narrow with Increasing Duration of Anti-Retroviral Therapy in HIV Infection: A Novel Estimator of Vascular Risk in HIV?

Objectives

HIV infection is associated with an increased risk of age-related morbidity mediated by immune dysfunction, atherosclerosis and inflammation. Changes in retinal vessel calibre may reflect cumulative structural damage arising from these mechanisms. The relationship of retinal vessel calibre with clinical and demographic characteristics was investigated in a population of HIV-infected individuals in South Africa.

Methods

Case-control study of 491 adults ≥30 years, composed of 242 HIV-infected adults and 249 age- and gender-matched HIV-negative controls. Retinal vessel calibre was measured using computer-assisted techniques to determine mean arteriolar and venular diameters of each eye.

Results

The median age was 40 years (IQR: 35–48 years). Among HIV-infected adults, 87.1% were receiving highly active antiretroviral therapy (HAART) (median duration, 58 months), their median CD4 count was 468 cells/µL, and 84.3% had undetectable plasma viral load. Unadjusted mean retinal arteriolar diameters were 163.67±17.69 µm in cases and 161.34±17.38 µm in controls (p = 0.15). Unadjusted mean venular diameters were 267.77±18.21 µm in cases and 270.81±18.98 µm in controls (p = 0.07). Age modified the effect of retinal arteriolar and venular diameters in relation to HIV status, with a tendency towards narrower retinal diameters in HIV cases but not in controls. Among cases, retinal arteriolar diameters narrowed with increasing duration of HAART, independently of age (167.83 µm <3 years of HAART vs. 158.89 µm >6 years, p-trend = 0.02), and with a HIV viral load >10,000 copies/mL while on HAART (p = 0.05). HIV-related venular changes were not detected.

Conclusions

Narrowing of retinal arteriolar diameters is associated with HAART duration and viral load, and may reflect heightened inflammatory and pro-atherogenic states of the systemic vasculature. Measurement of retinal vascular calibre could be an innovative non-invasive method of estimating vascular risk in HIV-infected individuals.     

Is Food Insecurity Associated with HIV Risk? Cross-Sectional Evidence from Sexually Active Women in Brazil

Background

Understanding how food insecurity among women gives rise to differential patterning in HIV risks is critical for policy and programming in resource-limited settings. This is particularly the case in Brazil, which has undergone successive changes in the gender and socio-geographic composition of its complex epidemic over the past three decades. We used data from a national survey of Brazilian women to estimate the relationship between food insecurity and HIV risk.

Methods and Findings

We used data on 12,684 sexually active women from a national survey conducted in Brazil in 2006–2007. Self-reported outcomes were (a) consistent condom use, defined as using a condom at each occasion of sexual intercourse in the previous 12 mo; (b) recent condom use, less stringently defined as using a condom with the most recent sexual partner; and (c) itchy vaginal discharge in the previous 30 d, possibly indicating presence of a sexually transmitted infection. The primary explanatory variable of interest was food insecurity, measured using the culturally adapted and validated Escala Brasiliera de Segurança Alimentar. In multivariable logistic regression models, severe food insecurity with hunger was associated with a reduced odds of consistent condom use in the past 12 mo (adjusted odds ratio [AOR] = 0.67; 95% CI, 0.48–0.92) and condom use at last sexual intercourse (AOR = 0.75; 95% CI, 0.57–0.98). Self-reported itchy vaginal discharge was associated with all categories of food insecurity (with AORs ranging from 1.46 to 1.94). In absolute terms, the effect sizes were large in magnitude across all outcomes. Underweight and/or lack of control in sexual relations did not appear to mediate the observed associations.

Conclusions

Severe food insecurity with hunger was associated with reduced odds of condom use and increased odds of itchy vaginal discharge, which is potentially indicative of sexually transmitted infection, among sexually active women in Brazil. Interventions targeting food insecurity may have beneficial implications for HIV prevention in resource-limited settings. Please see later in the article for the Editors'' Summary     

HIV Prevalence and Incidence in a Cohort of Women at Higher Risk for HIV Acquisition in Chókwè, Southern Mozambique

Background

Reliable HIV incidence estimates for Mozambique are limited. We conducted a prospective HIV incidence study as part of a clinical research site development initiative in Chókwè district, Gaza Province, southern Mozambique.

Methods

Between June 2010 and October 2012, we recruited women at sites where women at higher risk of HIV infection would likely be found. We enrolled and tested 1,429 sexually active women in the screening phase and 479 uninfected women in the prospective phase. Participants were scheduled for 12+ months follow-up, when they underwent face-to-face interviews, HIV counseling and testing, and pregnancy testing. We observed a total of 373.1 woman-years (WY) of follow-up, with mean (median) of 9.4 (9.7) women-months per participant.

Results

The prevalence of HIV was 29.4% (95% confidence interval [CI]: 27.0–31.8%). In multivariable logistic regression analysis, factors that remained significantly associated with prevalent HIV were: older age (OR: 0.6; 95% CI: 0.4–0.7), lower educational level (OR: 0.4; 95% CI: 0.3–0.7), and using hormonal contraception (OR: 0.6; 95% CI: 0.4–0.7) or condoms (OR: 0.5; 95% CI: 0.3–0.7). We observed an HIV incidence rate of 4.6 per 100 WY (95% CI: 2.7, 7.3). The HIV incidence was 4.8 per 100 WY (95% CI: 2.5, 8.3) in women aged 18–24 years, 4.5 per 100 WY (95% CI: 1.2, 11.4) in women aged 25–29 years and 3.2 per 100 WY (95% CI: 0.1, 18.0) in the 30–35 years stratum. None of the demographic factors or time-varying behavioral factors examined was significantly associated with incident HIV infection in bivariable analysis at p≤0.10.

Conclusions

We found a high HIV incidence among sexually active young women in Chókwè, Mozambique. HIV prevention programs should be strengthened in the area, with more comprehensive reproductive health services, regular HIV testing, condom promotion, and messaging about multiple sexual partners.     

Soil Microbial Communities and Ecological Risk Assessment: Risk Assessors’ Perspective

In the past, ecological risk assessments (ERAs) have generally overlooked the soil microbial community when evaluating the impacts of contaminants in soil. However, the soil microbial community, which includes bacteria and fungi, performs functions necessary for overall ecosystem health, including nitrogen fixation, nutrient cycling, and even degradation of contaminants. The incorporation of the soil microbial community into ERA requires the compilation of adequate toxicity data to complete the hazard assessment phase of the risk assessment. A variety of soil microbial toxicity tests exist that provide rapid and inexpensive results. Surveys of the microbial community at a contaminated site may also provide insight as to their functioning in the presence of contaminants. This paper explores the use of toxicity tests and surveys to evaluate chemical toxicity to microbes. However, many questions related to the best methodological approach to an ERA of the soil microbial community have yet to be answered.     

HIV Incidence and Risk Factors in Chinese Young Men Who Have Sex with Men—A Prospective Cohort Study

Objectives

To assess HIV incidence and its associated risk factors among young men who have sex with men (YMSM) in urban areas, China.

Design

The study used a prospective cohort study design and standard diagnostic tests.

Methods

A twelve-month prospective cohort study was conducted among YMSM (18–25 years old) in 8 large cities in China. The participants were recruited via snowball sampling. A total of 1102 HIV-negative YMSM completed baseline assessment, 878 YMSM participants completed 6-month follow-up, and 902 completed 12-month follow-up. HIV was screened by an enzyme-linked immunosorbent assay and confirmed with Western Blot. Syphilis was screened via rapid plasma reagent and confirmed by treponema pallidum particle agglutination assay.

Results

78 HIV seroconversions were identified within 1168.4 person-year observations yielding an incidence rate of 6.7 per 100 person-years. HIV seroconversion was associated with non-student status (RR = 2.61, 90% CI = 1.3–5.26), low HIV transmission knowledge (RR = 8.87, 90% CI = 2.16–36.43), and syphilis infection (RR = 5.04, 90% CI = 2.57–9.90).

Conclusions

Incidence of HIV among YMSM is high in urban areas of China. Interventions measures are required to contain the HIV epidemic within this population.     

Nanotechnology—Life-Cycle Risk Management

Scientists, risk practitioners, and regulators have debated the need to be proactive in assessing the potential health and environmental risks and benefits of unregulated nano-scale technologies. Many nanotech-based products and applications are already in use or development. Application of a proactive risk-based approach that considers the life cycle of the product, rather than a precautionary principle approach that would likely restrict the progress and advance of nanoscience, will be useful in helping to assess the unknown and unpredictable risks associated with nano-products, nanotoxicity, and nanopollution.

This article summarizes what is currently known regarding the potential toxicity and hazards of nanomaterials. A life-cycle perspective is used to identify important areas for further consideration and research. A conceptual framework is proposed for linking the strategies of life cycle and risk analysis within the same toolbox. This approach allows for prevention and treatment of a material's life-cycle risks, which can be considered in an integrated manner, thereby promoting continuous improvement, proactive risk reduction, and a flexible and adaptive approach to evaluating nanotechnology without stifling innovation.     

HIV Incidence in a Cohort of Women at Higher Risk in Beira,Mozambique: Prospective Study 2009–2012

Background

HIV is prevalent in Sofala Province, Mozambique. To inform future prevention research, we undertook a study in the provincial capital (Beira) to measure HIV incidence in women at higher risk of HIV and assess the feasibility of recruiting and retaining them as research participants.

Methods

Women age 18–35 were recruited from schools and places where women typically meet potential sexual partners. Eligibility criteria included HIV-seronegative status and self-report of at least 2 sexual partners in the last month. History of injection drug use was an exclusion criterion, but pregnancy was not. Participants were scheduled for monthly follow-up for 12 months, when they underwent face-to-face interviews, HIV counseling and testing, and pregnancy testing.

Results

387 women were eligible and contributed follow-up data. Most were from 18–24 years old (median 21). Around one-third of participants (33.8%) reported at least one new sexual partner in the last month. Most women (65.5%) reported not using a modern method of contraception at baseline. Twenty-two women seroconverted for a prospective HIV incidence of 6.5 per 100 woman-years (WY; 95% confidence interval (CI): 4.1–9.9). Factors associated with HIV seroconversion in the multivariable analysis were: number of vaginal sex acts without using condoms with partners besides primary partner in the last 7 days (hazard ratio (HR) 1.7; 95% CI: 1.2–2.5) and using a form of contraception at baseline other than hormonal or condoms (vs. no method; HR 25.3; 95% CI: 2.5–253.5). The overall retention rate was 80.0% for the entire follow-up period.

Conclusions

We found a high HIV incidence in a cohort of young women reporting risky sexual behavior in Beira, Mozambique. HIV prevention programs should be strengthened. Regular HIV testing and condom use should be encouraged, particularly among younger women with multiple sexual partners.     

Repeat Cardiovascular Risk Assessment after Four Years: Is There Improvement in Risk Prediction?

Background

Framingham risk equations are widely used to predict cardiovascular disease based on health information from a single time point. Little is known regarding use of information from repeat risk assessments and temporal change in estimated cardiovascular risk for prediction of future cardiovascular events. This study was aimed to compare the discrimination and risk reclassification of approaches using estimated cardiovascular risk at single and repeat risk assessments

Methods

Using data on 12,197 individuals enrolled in EPIC-Norfolk cohort, with 12 years of follow-up, we examined rates of cardiovascular events by levels of estimated absolute risk (Framingham risk score) at the first and second health examination four years later. We calculated the area under the receiver operating characteristic curve (aROC) and risk reclassification, comparing approaches using information from single and repeat risk assessments (i.e., estimated risk at different time points).

Results

The mean Framingham risk score increased from 15.5% to 17.5% over a mean of 3.7 years from the first to second health examination. Individuals with high estimated risk (≥20%) at both health examinations had considerably higher rates of cardiovascular events than those who remained in the lowest risk category (<10%) in both health examinations (34.0 [95%CI 31.7–36.6] and 2.7 [2.2–3.3] per 1,000 person-years respectively). Using information from the most up-to-date risk assessment resulted in a small non-significant change in risk classification over the previous risk assessment (net reclassification improvement of -4.8%, p>0.05). Using information from both risk assessments slightly improved discrimination compared to information from a single risk assessment (aROC 0.76 and 0.75 respectively, p<0.001).

Conclusions

Using information from repeat risk assessments over a period of four years modestly improved prediction, compared to using data from a single risk assessment. However, this approach did not improve risk classification.     

High Risks of HIV Transmission for Men Who Have Sex with Men — A Comparison of Risk Factors of HIV Infection among MSM Associated with Recruitment Channels in 15 Cities of China

Objective

While the HIV epidemic varies greatly by region and population group throughout China, the HIV incidence among men who have sex with men (MSM) continues to rise at an alarmingly fast pace. We seek to analyze the risk factors associated with HIV infection among MSM recruited from different channels in large urban centers across China, in an attempt to shed light on the design of future targeted intervention strategies.

Methods

A total of 33,684 MSM from 14 cities and one province were recruited from July to December 2011. Demographic (e.g. age, marital status, education) and behavioral (e.g. condom use, HIV testing history) data were collected using information collection cards. Blood samples were also collected to test for HIV and Syphilis.

Results

Participants were recruited from five different channels, and all demonstrated distinct characteristics. The overall rate of positive HIV screening was 6.27% and the rate of syphilis infection was 6.50%. Participants recruited from bathhouses had the highest HIV (11.80%) and syphilis infection rates (11.20%). Participants who were infected with syphilis had the highest HIV-positive screening rate (13.75%; 95% CI OR, 2.33-3.06). living in the southwest region of the country (11.64%; OR=2.76, 95%CI OR 2.19-3.47), Being >20 years of age (P<0.001), living in the southwest region of the country (OR=2.76, 95%CI 2.19-3.47), not having sex with female over the previous 3 months (OR=1.27, 95%CI 1.09-1.48), no condom use during the last anal intercourse (OR=1.54, 95%CI 1.39-1.70) and other factors were all associated with a higher probability of having an HIV-positive test result.

Conclusion

Depending on the way they are recruited, more targeted interventions are required to prevent the spread of HIV/AIDS among MSM with different characteristics and behaviors. Results from this study could provide evidence for researchers to conduct further studies and policy-makers to establish more effective and strategic interventions for MSM in China.     

Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion

Objective

Investigation of the interplay between the CCR5 Δ32/wt genotype and demographic, epidemiological, clinical and immunological factors associated with mortality in the cART era.

Design

Longitudinal data from 507 HIV-infected patients following the Δ32 allele detection were analyzed.

Methods

Cumulative 15 years mortality was calculated using Kaplan-Meyer methodology. Hazard ratios were estimated using univariate Cox models. Basing on Akakie information criteria and statistical significance multivariate Cox model was constructed and effect plots presenting adjusted hazard ratio time-dependency were drawn. Analysis of the association of all-cause mortality and CCR5 Δ32/wt genotype prior to the antiretroviral treatment (cART) initiation (n = 507) and on the therapy (n = 422) was also performed.

Results

A mortality rate of 2.66 (CI 2.57–3.19) per 100 person-years was observed. Univariate analysis factors modifying the risk of death included the CCR5 genotype, gender, history of cART, AIDS diagnosis and also CD4 lymphocyte nadir, zenith, the latest CD4 count and stable levels >500 cells/µl. For multivariate analysis the following predictors were selected: CCR5 genotype (HR for wt/wt 2.53, CI 1.16–5.53, p = 0.02), gender (HR for males 1.91, 95%CI 1.1–3.36, p = 0.023), introduction of combined antiretroviral treatment (HR 4.85, CI 3.0–7.89, if untreated or treated <1 month, p<0.0001) CD4 count of 500 cells/µl for six months or more (HR 4.16, CI 1.95–8.88 if not achieved, p = 0.028), the latest CD4 count (HR 5.44, CI 3.39–8.74 for <100 cells/µl, p<0.0001) and history of AIDS (HR 1.69, CI 1.03–2.79, p = 0.039). Among untreated individuals the Δ32/wt genotype was associated with notably better survival (p = 0.026), while among cART treated individuals the Δ32 mutation did not correlate significantly with higher survival rates (p = 0.23).

Conclusions

The Δ32 CCR5 allele is associated with a reduction of the risk of all-cause mortality in HIV (+) patients alongside clinical and immunologic predictors such as AIDS, history of cART, lymphocyte CD4 cell count and gender.     

Is There an Increased Risk of Post-Operative Surgical Site Infection after Orthopaedic Surgery in HIV Patients? A Systematic Review and Meta-Analysis

Background

There is dilemma as to whether patients infected with the Human Immunodeficiency Virus (HIV) requiring implant orthopaedic surgery are at an increased risk for post-operative surgical site infection (SSI). We conducted a systematic review to determine the effect of HIV on the risk of post-operative SSI and sought to determine if this risk is altered by antibiotic use beyond 24 hours.

Methods

We searched electronic databases, manually searched citations from relevant articles, and reviewed conference proceedings. The risk of postoperative SSI was pooled using Mantel-Haenszel method.

Results

We identified 18 cohort studies with 16 mainly small studies, addressing the subject. The pooled risk ratio of infection in the HIV patients when compared to non-HIV patients was 1.8 (95% Confidence Interval [CI] 1.3–2.4), in studies in Africa this was 2.3 (95% CI 1.5–3.5). In a sensitivity analysis the risk ratio was reduced to 1.4 (95% CI 0.5–3.8). The risk ratio of infection in patients receiving prolonged antibiotics compared to patients receiving antibiotics for up to 24 hours was 0.7 (95% CI 0.1–4.2).

Conclusions

The results may indicate an increased risk in HIV infected patients but these results are not robust and inconclusive after conducting the sensitivity analysis removing poor quality studies. There is need for larger good quality studies to provide conclusive evidence. To better develop surgical protocols, further studies should determine the effect of reduced CD4 counts, viral load suppression and prolonged antibiotics on the risk for infection.     

狡猾的HIV

世界与我国艾滋病概况艾滋病病毒无疑是人类遇到的最强大的对手之一。到2004年全球累积艾滋病病毒感染者人数为7000多万。其中已经有3000多万人死亡,目前存活的感染者大约为3800万～4200万。由于大多数发达国家重视得比较早,采用宣传教育等干预措施及辅助药物治疗等手段,艾滋病在发达国家的流行势头比较低,而发展中国家则集中了绝大多数艾滋病病毒感染者。美国目前感染者大约为90万,俄罗斯大约为100万,而非洲大约有2000多万,印度约为500多万。     

HIV疫苗研究进展

自从1983年发现人类免疫缺陷病毒(Human immunodeficiency virus,HIV)以来,HIV一直以惊人的速度在全球蔓延,感染HIV的人数也日益增多.到目前为止,因患艾滋病死亡的人数已达到2500万,到2010年这一数字可能会突破8000万,因此研究预防和治疗艾滋病的药物也正日益迫切地摆在人们面前.