Early Stages Of HIV Infection Research Articles

Early HIV infection is associated with reduced proportions of gamma delta T subsets as well as high creatinine and urea levels.

Renal dysfunctions are major predictors of co-morbidities and mortality in HIV-infected individuals. Unconventional T cells have been shown to regulate kidney functions. However, there is dearth of information on the effect of HIV-associated nephropathies on γδ and DN T cells. It is also not clear whether γδ T cell perturbations observed during the early stages of HIV infection occur before immune activation. In this study, we investigated the relationship between creatinine and urea on the number of unconventional T cells in HIV-infected individuals at the early and chronic stages of infection. Persons in the chronic stage of infection were divided into treatment naïve and exposed groups. Treatment exposed individuals were further subdivided into groups with undetectable and detectable HIV-1RNA in their blood. Creatinine and urea levels were significantly higher among persons in the early HIV infection compared with the other groups. Proportions of γδ T, γδ+CD8, γδ+CD16 cells were also significantly reduced in the early stage of HIV infection (P<.01). Markers of immune activation, CD4+HLA-DR and CD8+HLA-DR, were also significantly reduced during early HIV infection (P<.01). Taken together, our findings suggest that high levels of renal markers as well as reduced proportions of gamma delta T cells are associated with the early stages of HIV infection. This event likely occurs before systemic immune activation reaches peak levels. This study provides evidence for the need for early HIV infection diagnosis and treatment.

In vitro replicative fitness of early Transmitted founder HIV-1 variants and sensitivity to Interferon alpha

Type I interferons, particularly interferon-alpha (IFN-α), play a vital role in the host's anti-viral defenses by interfering with viral replication. However, the virus rapidly evolves to exploit the IFN-α response for its replication, spread, and pathogenic function. In this study, we attempted to determine IFN-α susceptibility and productivity of infectious transmitted/founder (TF) (n = 8) and non-transmitted (NT) viruses (n = 8) derived from HIV-1 infected infants. Independent experiments were carried out to determine IFN-α resistance, replication fitness, and viral productivity in CD4+ T cells over a short period. In vitro studies showed that TF viruses were resistant to IFN-α during the very near moment of transmission, but in the subsequent time points, they became susceptible to IFN-α. We did not observe much difference in replicative fitness of the TF viruses in cultures treated with and without IFN-α, but the difference was significant in the case of NT viruses obtained from the same individual. Despite increased susceptibility to IFN-α, NT viruses produced more viral particles than TF viruses. Similar results were also obtained in cultures treated with maraviroc (MVC). The study identified unique characteristics of TF viruses thus prompting further investigation into virus-host interaction occurring during the early stages of HIV infection.

Bistable dynamics and Hopf bifurcation in a refined model of early stage HIV infection

Recent clinical studies have shown that HIV disease pathogenesis can depend strongly on many factors at the time of transmission, including the strength of the initial viral load and the local availability of CD4+ T-cells. In this article, a new within-host model of HIV infection that incorporates the homeostatic proliferation of T-cells is formulated and analyzed. Due to the effects of this biological process, the influence of initial conditions on the proliferation of HIV infection is further elucidated. The identifiability of parameters within the model is investigated and a local stability analysis, which displays additional complexity in comparison to previous models, is conducted. The current study extends previous theoretical and computational work on the early stages of the disease and leads to interesting nonlinear dynamics, including a parameter region featuring bistability of infectious and viral clearance equilibria and the appearance of a Hopf bifurcation within biologically relevant parameter regimes.

Interpreting HIV diagnostic histories into infection time estimates: analytical framework and online tool

BackgroundIt is frequently of epidemiological and/or clinical interest to estimate the date of HIV infection or time-since-infection of individuals. Yet, for over 15 years, the only widely-referenced infection dating algorithm that utilises diagnostic testing data to estimate time-since-infection has been the ‘Fiebig staging’ system. This defines a number of stages of early HIV infection through various standard combinations of contemporaneous discordant diagnostic results using tests of different sensitivity. To develop a new, more nuanced infection dating algorithm, we generalised the Fiebig approach to accommodate positive and negative diagnostic results generated on the same or different dates, and arbitrary current or future tests – as long as the test sensitivity is known. For this purpose, test sensitivity is the probability of a positive result as a function of time since infection.MethodsThe present work outlines the analytical framework for infection date estimation using subject-level diagnostic testing histories, and data on test sensitivity. We introduce a publicly-available online HIV infection dating tool that implements this estimation method, bringing together 1) curatorship of HIV test performance data, and 2) infection date estimation functionality, to calculate plausible intervals within which infection likely became detectable for each individual. The midpoints of these intervals are interpreted as infection time ‘point estimates’ and referred to as Estimated Dates of Detectable Infection (EDDIs). The tool is designed for easy bulk processing of information (as may be appropriate for research studies) but can also be used for individual patients (such as in clinical practice).ResultsIn many settings, including most research studies, detailed diagnostic testing data are routinely recorded, and can provide reasonably precise estimates of the timing of HIV infection. We present a simple logic to the interpretation of diagnostic testing histories into infection time estimates, either as a point estimate (EDDI) or an interval (earliest plausible to latest plausible dates of detectable infection), along with a publicly-accessible online tool that supports wide application of this logic.ConclusionsThis tool, available at https://tools.incidence-estimation.org/idt/, is readily updatable as test technology evolves, given the simple architecture of the system and its nature as an open source project.

Does sexual behaviour of people with HIV reflect antiretroviral therapy as a preventive strategy? A cross-sectional study among outpatients in Kenya

BackgroundThe World Health Organisation (WHO) advocates early initiation of HIV treatment as a prevention strategy among people living with HIV. There is strong evidence for the effectiveness of antiretroviral therapy (ART) as a preventive tool for HIV transmission. We aimed to determine the sexual behaviour of HIV outpatients and assess if it reflects the current preventive strategy for HIV transmission.MethodsWe conducted a cross-sectional study among adult (aged at least 18 years) patients with confirmed HIV diagnosis, and aware of their diagnosis, attending HIV outpatient care in Kenya. Data were gathered through self-report (using validated questionnaires) and file extraction. Multivariate logistic regression assessed the association between sexual risk taking behaviour controlling for gender, HIV clinical stage, HIV treatment status, Tuberculosis (TB) treatment status, and CD4 count.ResultsWe recruited n = 400 participants (n = 280[70%] female gender). The mean age was 39.4 (SD = 9.9) years. The mean CD4 count was 393.7 (SD = 238.2) and ranged from 2 to 1470 cells/mm3. N = 61 (15.64%) were on TB treatment. The majority (n = 366, 91.5%) were on ART. Just over half (n = 202, 50.5%) reported having a sexual partner. Of these n = 33 (16.1%) reported having unprotected sexual intercourse with a person of unknown HIV status in the previous 3 months.Multivariate analysis showed that participants not on ART (HIV treatment) were more likely to report unprotected sexual intercourse compared to those who were on ART (odds ratio .25, 95% CI .09 to .69; P = 0.007).Participants at early stage of HIV infection (stages 1/2) were more likely to report unprotected sexual intercourse compared to participants at advanced HIV infection (stages 3/4) (odds ratio .34, 95% CI .13 to .92; P = 0.035). Males participants were more likely to be involved in sexual risk taking behaviours compared to female participants (odds ratio .36, 95% CI .16 to .82; P = 0.015). TB treatment status, and CD4 count were not significantly associated with sexual risk taking.ConclusionParticipants not on ART have more unprotected sexual intercourse than those who are on ART. This calls for the need to scale up coverage and early ART initiation in order to reduce transmission of HIV.

Germinal centers B-cell reaction and T follicular helper cells in response to HIV-1 infection.

This review aims to summarize the recent findings on germinal center B-cell reaction and Tfh cells in HIV-1 infection, with particular emphasis on the spatial organization of the germinal center, follicular cell regulation, and cellular alterations resulting from HIV infection. HIV-specific bNAbs are generated by iterative cycles of B-cell maturation supported by GC environment. Recent observations underline that germinal center structural alterations at the earliest stages of HIV infection could impact Tfh cell and germinal center B-cell homeostasis, thus preventing the rise of efficient humoral immunity. Moreover, despite ART treatment, HIV-derived antigens persist, particularly in follicular CD4+ T cells. Antigenic persistence and variability lead to unregulated chronic stimulation. In this context, regulation of the germinal center appears of special interest. In addition to follicular T-regulatory cells (Tfr), new potent regulators of germinal center reaction, such as follicular CD8 T and NK cells have been recently identified. Altogether these new data provide a better understanding on how HIV infection severely impacts germinal center reaction. Here we propose several therapeutic approaches to promote the bNAb development in HIV-infected patients by improving the preservation of germinal center architecture and its regulation.

HIV-1 DNA sequence diversity and evolution during acute subtype C infection

Little is known about the genotypic make-up of HIV-1 DNA genomes during the earliest stages of HIV-1 infection. Here, we use near-full-length, single genome next-generation sequencing to longitudinally genotype and quantify subtype C HIV-1 DNA in four women identified during acute HIV-1 infection in Durban, South Africa, through twice-weekly screening of high-risk participants. In contrast to chronically HIV-1-infected patients, we found that at the earliest phases of infection in these four participants, the majority of viral DNA genomes are intact, lack APOBEC-3G/F-associated hypermutations, have limited genome truncations, and over one year show little indication of cytotoxic T cell-driven immune selections. Viral sequence divergence during acute infection is predominantly fueled by single-base substitutions and is limited by treatment initiation during the earliest stages of disease. Our observations provide rare longitudinal insights of HIV-1 DNA sequence profiles during the first year of infection to inform future HIV cure research.

Prevalence aetiology and clinical spectrum of abnormal adrenal functions in human immunodeficiency virus infection

Aim: To find Prevalence, Aetiology and Clinical Spectrum of abnormal adrenal functions in Human Immunodeficiency Virus infection. To diagnose and treat adrenal dysfunction in various stages of HIV infection and see the response to treatment if required.&#x0D; Material &amp; Methods: 100 patients with HIV infection being admitted to our hospital was evaluated for abnormal adreno cortical functions. Immune dysfunction was assessed with CD4 count. Statistical tests (chi squared test) were applied to the collected data to find out any significant correlations.&#x0D; Results: The overall prevalence of adrenocortical abnormalities in HIV positive patients was 14% which included hypocortisolemia in 3% and hypercortisolemia in 11% of patients. Frequency of hypocortisolemia was significantly associated with presence of HIV infection with opportunistic infections and low CD4 counts (less than 50cells). In patients having hypercortisolemia, ONDST (Over night dexamethasone suppression test) was done and it showed reduction of serum cortisol to expected level (suppressed to &lt;1.8 mcg/dl). Adjustment disorders and drugs mainly efavirnz more than nevirapine was incriminated in the same.&#x0D; Conclusion: HPA axis dysfunction is frequently encountered in HIV infected patients. The commonest dysfunction was hypercortisolemia probably due to elevated cytokines. Hypercortisolemia is a feature of early stage HIV infection. The likelihood of adrenal insufficiency increases as the disease advances and patient enters a more immunocompromised state. Hypocortisolemia should be treated regardless of the existence of associated symptoms. Hypercortisolemia in the absence of features of Cushing’s syndrome is common and should not promote treatment or specific studies.

High polymorphism rates in well-known T cell epitopes restricted by protective HLA alleles during HIV infection are associated with rapid disease progression in early-infected MSM in China.

T cell epitopes restricted by several protective HLA alleles, such as B*57, B*5801, B*27, B*51 and B*13, have been very well defined over the past two decades. We investigated 32 well-known T cell epitopes restricted by protective HLA molecules among 54 Chinese men who have sex with men (MSM) at the early stage of HIV-1 infection. Subjects in our cohort carrying protective HLA types did not exhibit slow CD4 T cell count decline (P = 0.489) or low viral load set points (P = 0.500). Variations occurred in 96.88% (31/32) of the known wild-type epitopes (rate 1.85-100%), and the variation rates of the strains of two CRF01_AE lineages were significantly higher than those of non-CRF01_AE strains (76.82% vs. 48.96%, P = 0.004; 71.27% vs. 8.96%, P = 0.025). Subjects infected with CRF01_AE exhibited relatively rapid disease progression (P = 0.035). Therefore, the lack of wild-type protective T cell epitopes restricted by classic protective HLA alleles in CRF01_AE HIV-1 strains may be one of the reasons why rapid disease progression is observed in Chinese MSM with HIV-1 infection.

ASSESSMENT OF TOXIC ACTION OF VARIOUS TREATMENT REGIMENS FOR TUBERCULOSIS IN PATIENTS WITH HIV INFECTION

The Russian Federation is among the countries with a high burden of tuberculosis and the worsening epidemiological situation of HIV. In patients with HIV infection mortality from TB reaches 43-89%. The incidence of tuberculosis in patients with HIV infection is 21-37 times higher than in people without HIV infection, and in some studies, the risk of developing tuberculosis in the early stages of HIV infection is 113 times higher. The aim of this work is to determine the toxic effect of different treatment regimens for tuberculosis in patients with HIV infection. Patients (total number 200) with tuberculosis and HIV infection with different treatment regimens for tuberculosis were examined. Clinical and laboratory data were studied. It was established that the first standard treatment of tuberculosis had a more pronounced toxic effect on patients, which was manifested by a decrease in appetite, nausea, in some cases vomiting and febrile feverish reaction; had a greater damaging effect on cell membranes, which led to an increase in the activity of alkaline phosphatase and lactate dehydrogenase. However, this regimen of chemotherapy contributes to a reduction in cough with mucus and mucopurulent sputum secretion, dyspnea with physical activity, pain in the chest during breathing that had a more pronounced therapeutic effect. Increase in the level of phosphatidylethanolamine can be considered as a proven marker of the toxic effect of tuberculosis treatment under the first standard regimen.

HIV rapid screening tests and self-tests: Be aware of differences in performance and cautious of vendors.

BackgroundRapid tests for HIV testing are essential tools to achieve the 90-90-90 target of the World Health Organization. Many tests are available, some directly from websites. Evaluation of the performance of rapid tests, under close to real-life usage, is therefore needed to ensure accurate diagnosis in the context of the recommendation for their more widespread use.MethodNine third- (3G) or fourth-generation (4G) rapid screening tests or self-tests (two bought on websites), were evaluated on an extensive panel of 200 HIV-negative and 312 HIV-positive samples, representative of a wide variety of clinical situations and HIV genetic diversity. A whole blood reconstitution protocol was designed to simulate real-life usage of these tests in community-based and private settings.FindingsThe specificity was high (98.5–100%) and sensitivity excellent (100%) for samples from patients chronically infected with the pandemic strains. The performance for infrequent situations with a major epidemiological and clinical impact, such as infection with divergent viruses or primary infection, was highly variable, depending on the test. One of the two 4G tests allowed detection of additional positive samples from early stages of infection, whereas the second (sold as a 4G test on a website) corresponded in reality to a 3G test.InterpretationOur study showed that not all tests are equal for the detection of major HIV variants or early stages of HIV infection; adding the detection of specific p24Ag improved the latter point. This study also showed, for the first time, that buying through web-based vendors can be risky, due to the varying performance of the tests and questionable sales practices. Our results are of particular importance in the context of the increasing use of rapid tests in an “outside laboratory” settings.FundSanté Publique France, COREVIH – Normandie, and Rouen University Hospital.

Modulation of epigenetic factors during the early stages of HIV-1 infection in CD4+ T cells in vitro

Several studies have related epigenetic mechanisms to HIV-1 latency. However, the epigenetic modifications of the host cell genome involved in the early stages of HIV-1 infection remain unclear. This study aimed to investigate epigenetic factors that are regulated at the beginning of HIV-1 infection in activated and resting CD4+ T cells. We analyzed the gene expression of 84 epigenetic targets, global DNA methylation, and HIV-1 replication kinetics for 36 h after infecting CD4+ T cells obtained from the blood of twelve healthy donors. The epigenetic targets aurora kinase B (AURKB), aurora kinase C (AURKC) and DNA methyltransferase 3B (DNMT3B), and the global DNA methylation profile are regulated during HIV-1 replication in CD4+ T cells, and this regulation can be influenced by the activation state of the cell at the time of infection. Approaches that affect the expression of these epigenetic targets could help current strategies to suppress HIV-1 replication.

Estimating the mutational fitness effects distribution during early HIV infection.

The evolution of HIV during acute infection is often considered a neutral process. Recent analysis of sequencing data from this stage of infection, however, showed high levels of shared mutations between independent viral populations. This suggests that selection might play a role in the early stages of HIV infection. We adapted an existing model for random evolution during acute HIV-infection to include selection. Simulations of this model were used to fit a global mutational fitness effects distribution to previously published sequencing data of the env gene of individuals with acute HIV infection. Measures of sharing between viral populations were used as summary statistics to compare the data to the simulations. We confirm that evolution during acute infection is significantly different from neutral. The distribution of mutational fitness effects is best fit by a distribution with a low, but significant fraction of beneficial mutations and a high fraction of deleterious mutations. While most mutations are neutral or deleterious in this model, about 5% of mutations are beneficial. These beneficial mutations will, on average, result in a small but significant increase in fitness. When assuming no epistasis, this indicates that, at the moment of transmission, HIV is near, but not on the fitness peak for early infection.

Occurrence of APOBEC3G variations in West Indian HIV patients

The genetic variations in APOBEC3G gene are correlated with HIV disease progression. These variations differ in different ethnic groups. The prevalence of APOBEC3G (-90C/G, −571G/C) variations have not been studied in Indian population. Hence, we assessed the occurrence of APOBEC3G polymorphisms in HIV patients and its association with acquisition of HIV and disease progression. Polymorphisms in APOBEC3G were genotyped in a total of 153 HIV patients, naïve to ARV and 156 healthy controls by PCR-RFLP method. In single locus model, the frequency of distribution of APOBEC3G −90CG, −571 GC genotypes were higher in HIV patients as compared to healthy controls (57.5% vs. 50.0%, OR = 1.22; 17.0% vs. 12.8%, OR = 1.39). In double locus model, the dominant −571 GC + CC genotype was distributed at a much higher frequency in HIV patients as compared to healthy controls (18.3% vs. 14.1%, OR = 1.50). The frequency of APOBEC3G −571CC and CC + GC genotypes were higher in early HIV disease stage as compared to healthy controls (23.9% vs. 12.8%, OR = 2.23, P = 0.08; 28.3% vs. 14.1%, OR = 2.40, P = 0.04). APOBEC3G-571 GC and GC + CC genotypes were more prevalent in HIV patients consuming tobacco and alcohol as compared to non-users (22.7% vs. 15.3%, OR = 1.71, P = 0.56; 27.3% vs. 16.5%, OR = 1.90, P = 0.39 and 31.6% vs. 13.6%, OR = 2.31, P = 0.08; 36.8% vs14.8%, OR = 2.49, P = 0.04, respectively). In conclusion, APOBEC3G-571G/C polymorphism was associated with the early stage of HIV infection and could potentially influence HIV disease progression in alcohol users. The distribution of APOBEC3G polymorphisms and its haplotypes were not significantly different between HIV patients and healthy controls.

J-102 Decreased levels of seroreactivity in individuals subjected to antiretroviral therapy early in acute HIV infection

WHO guidelines recommend antiretroviral treatment (ART) of all HIV infected individuals regardless of CD4 count. Early treatment minimizes the risk of HIV transmission, lowers the natural reservoir of the virus, and reduces subsequent serious AIDS related events, but may also disrupt emergence of HIV diagnostic markers. High-risk individuals at early stages of HIV infection, (HIV-1 RNA positive, Western Blot negative or indeterminate), were enrolled into an IRB approved study to examine the outcomes of early HAART initiation. Plasma samples collected at week 0, 2, 12, and 24 were tested by EIA 1/2 Plus O, HIV-1/2 Ag/Ab Combo, HIV-1/2 MultiSpot (MS), and HIV-1 Western Blot (WB) (all from Bio-Rad, Redmond, WA). HIV Viral Load was determined by Abbott m2000 HIV-1 RT PCR (Chicago, IL). Stage of HIV infection was based on the Fiebig staging system. Of individuals treated at Fiebig I and II, 63.6 and 59.1%, respectively, were antibody negative at 12 weeks. At week 12, MS was reactive in 18.2%, 53.7% and 35.0% of individuals treated at Fiebig I, II, and Fiebig III/IV, and decreased to 9.1%, 48.4% and 30.0%, respectively, by week 24. 52.9% of individuals treated at Fiebig III/IV were negative at week 24. In contrast, all untreated individuals were highly reactive by EIA, WB, MS and RNA by week 2–3 after infection and remained reactive thereafter. Absence of serological markers in individuals treated early in infection presents challenges in determining status of infection, as some individuals under therapy may test serologically non-reactive and RNA negative, but are infected. These findings may also have implications in monitoring individuals on Pre-exposure Prophylactics (PrEP) by serological tests alone.

Early HIV infection predictions: role of viral replication errors.

In order to prevent and/or control infections it is necessary to understand their early-time dynamics. However this is precisely the phase of HIV about which the least is known. To investigate the initial stages of HIV infection within a host we have developed a multi-type, continuous-time branching process model. This model is a stochastic extension of the standard viral dynamics model, under the assumption that the number of cell targets for viral infection is constant, biologically reasonable since, during the earliest stages of HIV infection, very few cells are infected relative to their total population size. We use our model to investigate three important clinical characteristics of early HIV infection following intravenous challenge: risk of infection, time to infection clearance (assuming failed infection), and time to infection detection. Our focus is on the impact of errors in viral replication that result in non-infectious virus production on these characteristics. Only a small fraction of circulating virus in any chronically infected individual is capable of infecting susceptible cells: estimates range from 1/104 - 1/103. Characterization and quantification of the processes by which virus becomes defective remains incomplete. We consider two mechanisms that result in defective virus: (1) Copying errors, i.e., lethal errors in reverse transcription, which introduce mutations into the HIV-1 proviral genome, some of which may cripple the viral genome produced, and (2) Packaging errors, i.e., errors during viral packaging, at the end of the viral replication cycle, which cause defective virus by packaging new virions without, for example, viral RNA or key proteins required for infectivity. We show that assumptions on mechanisms of defective virus production can significantly impact early HIV infection model predictions. For example, the risk of infection is orders of magnitude higher if all defective virus is associated with packaging errors, but infection is predicted to be detectable sooner following HIV exposure if all defective virus is associated with copying errors. Thus, in order to make reliable predictions of risk, clearance time, and detection time, better characterization of viral replication is required.

High Incidence of Pulmonary Tuberculosis in ART Naive Remunerated Blood Donors with Human Immunodeficiency Virus Type-1 Infection: Possible Role of Iron Overload

Iron overload is reported to be associated with immune alterations and increased susceptibility to infections. HIV infection is characterized by progressive immunodeficiency leading to invasion by opportunistic pathogens. It was of interest to find out if disease course in HIV type-1 infection could have any relation with alteration in body iron status among individuals with history of oral iron intake. A follow-up study of immunologic and virologic markers in relation to disease progression was undertaken on asymptomatic HIV-1 positive blood donors with history of oral iron intake (subgroup I) compared to those without such history (subgroup II). High serum iron was associated with elevated levels of Th2 category of cytokines, heightened immune activation, faster decline in CD4 + T lymphocyte count and higher viral set point. Pulmonary tuberculosis (PT) was the most common AIDS related illness (ARI) (>70%) recorded among subgroup I compared to non-PT category of ARI. Median ARI free duration (months) was shorter among those who developed PT compared to those developing non-PT category of ARI i.e. 30 (95% CI as 26,32) versus 67(95% CI as 60,71) in subgroup I and 47 (95% CI as 42,49) versus 80 (95% CI as 72,87) in subgroup II (P P < 0.001 for PT versus non-PT in both subgroups). The present study indicates that body iron overload resulting from excess intake of iron may be associated with qualitative defects in cell mediated immunity at early stage of HIV-1 infection that may facilitate subsequent acquisition of pulmonary tuberculosis, shorter ARI free duration and reduced survival.

Early HIV infection among persons referred for malaria parasite testing in Nigeria

Persons in the early stages of HIV infection are the major drivers of new infections. These individuals may also develop renal dysfunctions at this time. Nigeria, as other African countries, has one of the highest prevalenceof newly diagnosed HIV infections. Despite this, limited information exists on early HIV detection in the continent. This may berelated to difficulties in providing early HIV diagnosis and treatment. Patients referred for malaria testing may provide a unique opportunity for early HIV detection. In this study, a method for identifying early HIV-infected individuals was assessed. HIV-1 subtype and renal function biomarkers were also analyzed in these persons. To identify early HIV infection, over a period of 18months blood samples were collected from persons referred by clinicians for malaria parasite tests in Nigeria. A total of 671 samples were collected and analyzed for HIV antigen/antibody and subtypes. 101 of these samples were categorized into one of four groups: early HIV, chronic HIV, malaria infection and control groups for renal function analysis. 29% of HIV infected individuals were at the early stages of infection. The predominant subtype detected was CRF02_AG (57.14%). The early HIV group had the highest mean serum creatinine (95µmol/L) and urea (5.7mmol/L) values across all groups with the difference significant at P<0.05. There was no significant difference between the circulating subtype and the stage of HIV infection. Our results show the feasibility of screening persons referred for malaria tests for early HIV. This can be used to control new HIV infections in sub-Saharan Africa.

Association of age and time of disease with HIV-associated neurocognitive disorders: a Japanese nationwide multicenter study.

There is no detailed information on the association between age, time of disease, and HIV-associated neurocognitive disorders (HAND). In this prospective study involving 17 medical facilities across Japan, we recruited HIV-infected patients to complete a 14-test neuropsychological battery that assess eight neurocognitive domains. HAND were diagnosed by the Frascati criteria. Of 1399 recruited patients, 728 were enrolled. The prevalence of HAND was 25.3% [13.5% asymptomatic neurocognitive impairment, 10.6% mild neurocognitive disorder (MND), and 1.2% HIV-associated dementia (HAD)]. Tests that assess executive and visuospatial functions showed better diagnostic accuracy than other tests for HAND. Multivariate analysis identified age (≥50years) and incomplete virological suppression as risk factors for MND and HAD and current ART as a protective factor. The prevalence of MND and HAD was low in the early stage of infection (6.3% in ≥2 to <6years), then increased in the later stage [17.3% in ≥11years, p=0.001 (vs. ≥2 to <6years)], independent of age or treatment. Older patients were more likely to show MND or HAD in the early stage of HIV infection (26.7 vs. 8.7% for <2years and 17.4 vs. 3.1% for ≥2 to <6years, p=0.040 and 0.004, respectively) compared to younger ones. In conclusion, MND and HAD were more commonly found in later years since diagnosis of HIV infection and older patients are at risk of neurocognitive impairment at the early stage of HIV infection. Tests for executive and visuospatial functions seem more sensitive than other tests for diagnosing HAND.

Reduced intraepidermal nerve fiber density in early stage of HIV infection

Small fiber neuropathic pain is one of the clinical manifestations which usually develop in late stage of HIV infection. Research on small fiber neuropathic pain in early stage HIV infection has not been established. Lack of small fiber neuropathic pain in early stage of HIV infection data proves the need of more study. This can be proven by Intraepidermal Nerve Fiber (IENF) density skin biopsy examination.