HIV-1 superinfection can occur in the presence of broadly neutralizing antibodies

BackgroundSuperinfection of individuals already infected with HIV-1 suggests that pre-existing immune responses may not adequately protect against re-infection. We assessed high-risk female sex workers initially infected with HIV-1 clades A, D or A/D recombinants, to determine if HIV-1 broadly neutralizing antibodies were lacking prior to superinfection.MethodsSix superinfected female sex workers previously stratified by HIV-1 high-risk behavior, infecting virus clade and volunteer CD4 counts were evaluated at baseline (n = 5) and at 350 days post-superinfection (n = 6); one superinfected volunteer lacked pre-superinfection plasma. Retrospective plasmas were assessed for neutralization of a multi-clade panel of 12 HIV-1 viruses before superinfection, and then at quarterly intervals thereafter. Similarly stratified singly infected female sex workers were correspondingly assessed at baseline (n = 19) and 350 days after superinfection (n = 24). Neutralization of at least 50% of the 12 viruses (broad neutralization), and geometric means of the neutralization titers (IC₅₀) were compared before and after superinfection; and were correlated with the volunteer HIV-1 superinfection status, CD4 counts, and pseudovirus clade.ResultsPreexisting broad neutralization occurred in 80% (4/5) of the superinfected subjects with no further broadening by 350 days after superinfection. In one of the five subjects, HIV-1 superinfection occurred when broad neutralization was lacking; with subsequent broadening of neutralizing antibodies occuring within 9 months and plateauing by 30 months after detection of superinfection. Clade B and C pseudoviruses were more sensitive to neutralization (13; [87%]); and (12; [80%]) than the locally circulating clades A (10; [67%]) and D (6; [40%]), respectively (p = 0.025). Low antibody titers correlated with clade D viruses and with >500 CD4 T cell counts, but not with the superinfection status.ConclusionThese data demonstrate that HIV-1 superinfection can occur both in the presence, and in the absence of broadly neutralizing antibodies.     

Perceived Access and Actual Intake of Healthy Diets Among Households in Vulnerable Salvadoran Communities

ObjectiveThis study aimed to examine the dietary intake of Salvadoran households according to perceived access to healthy meals (PAHD), and to identify household characteristics associated with diet quality and PAHD.MethodsSecondary data analysis with a sample of 139 Salvadoran households from resource-poor communities in El Salvador. Chi-square tests and ANOVA were used to assess differences in dietary intake across households classified according to PAHD.ResultsHigh-PAHD households had higher women's education, household food security levels, overall diet quality, and variety, and higher intakes of animal products, fats, cholesterol, vitamin C, and sodium (P < .05). Diet quality was not associated with the household characteristics studied.Conclusions and ImplicationsOverall diet quality was associated with higher levels of PAHD, but some differences in intakes were not as expected, such as higher intakes in foods and nutrients associated with low-quality diets, among high PAHD households.     

Estimating primary care attendance rates for fever in infants after meningococcal B vaccination in England using national syndromic surveillance data

BackgroundIn September 2015, the United Kingdom became the first country to introduce the multicomponent group B meningococcal vaccine (4CMenB) into a national infant immunisation programme. In early clinical trials 51–61% of infants developed a fever when 4CMenB was administered with other routine vaccines. Whilst administration of prophylactic paracetamol is advised, up to 3% of parents may seek medical advice for fever following vaccination. We used research-level general practitioner consultations to identify any increase in attendances for all-cause fever in vaccine-eligible infants following 4CMenB introduction in England.MethodsConsultations for infant all-cause fever in the year following the vaccine introduction were identified from The Phoenix Partnership (TPP) ResearchOne general practice database using Read (CTV3) codes. Average daily consultation rates and incidence rate ratios (IRRs) were calculated for vaccine-eligible age groups and compared to the two years preceding vaccine introduction. The difference between pre- and post-vaccine all-cause fever consultations was estimated.ResultsAll-cause fever consultations in vaccine-eligible 7–10 week olds were 1.6-fold higher (IRR, 1.58; 95% CI, 1.22–2.05) compared to the two previous years and 1.5-fold higher (IRR 1.47; 95% CI, 1.17–1.86) in 15–18 week-olds. There were no significant differences in 0–6 or 11–14 week-olds. Applying the difference between pre- and post-vaccine consultation rates to the 4CMenB vaccine-eligible age groups across England estimated 1825 additional fever consultations in the year following 4CMenB introduction.ConclusionsWe found a small but significant difference in all-cause fever consultation rates in vaccine-eligible infants who would have received 4CMenB with other vaccines.     

北京市朝阳区暗娼艾滋病性病综合干预效果分析

目的 探求艾滋病在大城区、低流行状况下降低暗娼人群感染艾滋病和（或）性病风险的综合防治措施。方法 采用问卷调查的方式对辖区内8家娱乐场所暗娼（female sex workers,FSW）干预前226名及干预后187名进行调查,采用χ^2检验进行统计学分析。结果 接受调查的FSW年龄范围在17-40岁[（25．22±5．81）岁];高中及初中文化程度达203名（89．82％）;未婚为166名（73．45％）,职业中无业者达205名（90．70％）;来自外省市224名（99．12％）。调查前后对性病、艾滋病防治知识的知晓率由52．6％提升至75．4％（χ^2=22．701,P〈0．01）,使刷安全套的比率由治疗前22．12％提升至34．76％（χ^2=8．14,P〈0．05）。结论 北京市朝阳区通过综合干预措施对于暗娼防治艾滋病和（或）性病取得了较为显著的效果,综合干预措施值得在大城区、低流行状况下的暗娼人群艾滋病性病干预中广泛应用。     

1989-2015年云南省德宏州50岁及以上HIV感染者流行病学特征分析

目的 分析云南省德宏州1989-2015年50岁人群艾滋病疫情特征及流行趋势。方法 收集国家艾滋病防治综合信息系统中报告现住址为云南省德宏州,年龄50岁的临床诊断和实验室诊断艾滋病病毒感染者/艾滋病患者（HIV/AIDS）,截止日期为2015年12月31日,对其构成比、三间分布和趋势构成变化等进行分析。结果 现住址累计报告50岁HIV/AIDS病例1 193例,占累计报告数的7.98%;1 193例病例中,截止2015年底已死亡496例,病死率为41.58%。自2000年以来50岁HIV/AIDS的构成比逐年上升,从2000年的2.97%上升至2015年的19.94%。50岁HIV/AIDS在全州5县均有分布,芒市占当地报告HIV/AIDS构成比最高（占11.67%）。50岁HIV/AIDS人群分布以男性为主（64.79%,773/1 193）,平均年龄（58.316.96）岁,93.38%患者的文化程度为初中及以下,94.02%的职业为农民、待业和离退休人员。89.52%通过性接触传播,10.48%通过注射吸毒传播。女性、无配偶者、性接触传播者、农民和临床就诊检测发现者所占比例在不同时间段（1989-2003年、2004-2011年和2012-2015年）呈现上升趋势。结论 德宏州50岁人群艾滋病流行形式较为严峻,艾滋病防控工作应关注该年龄人群,结合艾滋病防治常规工作开展多元化的性健康教育应成为该人群艾滋病防治工作的重心。     

Cost-Effectiveness of the NIMH Multisite HIV Prevention Intervention

The objective of this study was to evaluate the cost-effectiveness of a state-of-the-art sexual-risk reduction intervention for high-risk men and women. The main intervention consisted of seven small-group sessions based on well-established principles of cognitive–behavioral therapy. This intervention was compared with a single-session video-based risk reduction intervention. The main outcome measure was the incremental cost–utility ratio, which equals the additional cost per additional quality-adjusted life year (QALY) saved by the cognitive–behavioral intervention, in comparison with the video intervention. A mathematical model of HIV transmission was used to translate reported sexual behavior changes into estimates of the number of HIV infections averted by the interventions, and associated savings in QALYs and averted HIV-related medical costs. For women, the incremental cost–utility ratio equaled $32,688 per QALY saved, which indicates that the cognitive–behavioral intervention was cost-effective compared to the video intervention. For men, the incremental cost–utility ratio was slightly negative, suggesting that the cognitive–behavioral intervention was highly cost-effective, or even cost-saving, compared to the video intervention. This analysis indicates that both brief and intensive sexual risk reduction interventions for high-risk populations can be cost-effective.     

Immune activation and induction of HIV-1 replication within CD14 macrophages during acute Plasmodium falciparum malaria coinfection

OBJECTIVES: To determine the impact of Plasmodium falciparum malaria coinfection and its treatment on cellular reservoirs of viral replication in HIV-1-infected persons and to relate this to changes in systemic immune activation. METHODS: Plasma samples were obtained from HIV-1-infected individuals (n = 10) at diagnosis of acute malaria, 4 weeks after parasite clearance and from HIV-infected aparasitemic controls (n = 10). Immunomagnetic HIV-1 capture analysis was used to determine the cellular origin of cell-free virus particles present in all 30 plasma samples and indices of immune activation were measured using enzyme-linked immunosorbent assays. RESULTS: Compared with controls, the detectable proportion of HIV-1 particles derived from CD14 macrophages and CD26 lymphocytes was increased in persons with acute malaria coinfection and correlated with markedly increased plasma concentrations of both proinflammatory cytokines and soluble markers of macrophage and lymphocyte activation. Parasite clearance following treatment with antimalarial drugs resulted in decreased detection of HIV-1 particles derived from the CD14 macrophage cell subset and correlated with a marked diminution in systemic immune activation. CONCLUSIONS: Acute P. falciparum malaria coinfection impacts virus-host dynamics in HIV-1-infected persons at the cellular level, notably showing a reversible induction of HIV-1 replication in CD14 macrophages that is associated with changes in immune activation.     

Non‐neutralizing epitopes induce robust hepatitis C virus (HCV)‐specific antibody‐dependent CD56+ natural killer cell responses in chronic HCV‐infected patients

Natural killer (NK) cell‐mediated antibody‐dependent cellular cytotoxicity (NK‐ADCC) is of considerable interest in viral infection. However, little is known about NK‐ADCC responses in chronic hepatitis C virus (HCV) infection. In this study, impaired non‐specific antibody‐dependent CD56⁺ NK cell responses were observed in chronic HCV infection, as shown by decreased degranulation (extracellular CD107a expression) and interferon (IFN)‐γ production in response to antibody‐bound P815 cells. A peptide pool composed of epitopes recognized by anti‐HCV‐E1/E2 antibodies could induce pronounced HCV‐specific antibody‐dependent NK cell responses in sera from approximately half the chronic HCV carriers. Additionally, HCV‐specific epitopes with the capacity to induce robust NK‐ADCC activity were identified. Five linear NK‐ADCC epitopes (aa211‐aa217, aa384‐aa391, aa464‐aa475, aa544‐aa551 and aa648‐aa659 of the HCV envelope) were identified and do not overlap with putative linear neutralizing epitopes. This study revealed the dysfunctional characteristics of antibody‐dependent CD56⁺ NK cell responses in chronic HCV carriers. The key non‐neutralizing NK‐ADCC epitopes identified in this study may act as new targets for immunological intervention.