Acute HIV Infection Research Articles

A Longitudinal Analysis Reveals Early Activation and Late Alterations in B Cells During Primary HIV Infection in Mozambican Adults.

Primary HIV infection (PHI) and subsequent chronic infection alter B-cell compartment. However, longitudinal analysis defining the dynamics of B-cell alterations are still limited. We longitudinally studied B-cell subsets in individuals followed for 1 year after PHI (n = 40). Treated and untreated chronic HIV infected (n = 56) and HIV-uninfected individuals (n = 58) were recruited as reference groups at the Manhiça District in Mozambique. B cells were analyzed by multicolor flow-cytometry. Anti-HIV humoral response and plasma cytokines were assessed by ELISA or Luminex-based technology. A generalized activation of B cells induced by HIV occurs early after infection and is characterized by increases in Activated and Tissue-like memory cells, decreases in IgM-IgD- (switched) and IgM-only B cells. These alterations remain mostly stable until chronic infection and are reverted in part by ART. In contrast, other parameters followed particular dynamics: PD-1 expression in memory cells decreases progressively during the first year of infection, Transitional B cells expand at month 3–4 after infection, and Marginal zone-like B cells show a late depletion. Plasmablasts expand 2 months after infection linked to plasma viral load and anti-p24 IgG3 responses. Most of well-defined changes induced by HIV in B-cell activation and memory subsets are readily observed after PHI, lasting until ART initiation. However, subsequent changes occur after sustained viral infection. These data indicate that HIV infection impacts B cells in several waves over time, and highlight that early treatment would result in beneficial effects on the B-cell compartment.

Factors Associated with Medication Adherence for People Living with Acute HIV Infection in a Tertiary Chinese Hospital in Beijing.

Both the management and caregiving intervention of people living with HIV (PLWH), especially during acute HIV-1 infection, represent a public health issue and a form of social support. This current study analyzed the demographic and clinical factors associated with antiretroviral therapy (ART) adherence of PLWH from positive HIV diagnosis to ART initiation in a tertiary Chinese hospital in Beijing. A total of 200 participants diagnosed with acute HIV-1 infection were enrolled in this study. We collected demographic and clinical data by the use of a self-reported questionnaire. Bivariate and multivariate logistic regressions were used to determine associations between potential variables and outcomes. We found that medication adherence was impacted by years of ART and number of reminders (all P < 0.05). In addition, medication adherence was associated with viral load at 48 weeks (P = 0.035). Future studies are needed to investigate effective interventions that could facilitate ART adherence.

Ability of Alere™ HIV Combo to diagnose acute HIV infection is based mainly on HIV-1 p24 antigen detection.

Alere™ HIV Combo is the only rapid and sensitive point-of-care 4th generation (antigen/antibody) HIV test newly available in Thailand which is advantageous of differentiating between positivity of antigen or antibody or both, especially in acute HIV infection (AHI). AHI in this study was defined by positive machine-based 4th generation test with measurable HIV-RNA but negative 3rd generation (IgM/IgG antibody only) tests. To evaluate the performance characteristics of Alere™ HIV Combo. Fifty stored plasma samples of subjects diagnosed with AHI were used to evaluate Alere™ HIV Combo. Of the 50 AHI samples, Alere™ HIV Combo was positive in 37 (74%): 5 with antibody positive only (R1), 26 with p24 antigen positive only (R2), and 6 with both p24 antigen and antibody positive (R3). Mean sample/cut-off (S/ CO) ratios from machine-based 4th generation test of R1, R2 and R3 were 21.55, 148.38 and 72.97 respectively as compared to 7.57 for the 13 non-reactive (NR) samples. The corresponding median log10 HIV-RNA of NR, R1, R2 and R3 were 5.59, 5.86, 7.00 and 6.61 copies/mL respectively. R2 and R3 had significantly higher S/CO and HIV-RNA than NR and R1. Alere™ HIV Combo detected mainly p24 antigen in AHI as seen in 32/50 (64%) subjects and could detect 11/50 (22%) antibody in AHI samples which were missed by the two 3rd generation HIV tests used in our testing algorithm. Alere™ HIV Combo is the ideal screening test in a setting with high AHI where machine-based 4th generation test is not available.

Innate Immune Response Against HIV-1.

The innate immune system is comprised of both cellular and humoral players that recognise and eradicate invading pathogens. Therefore, the interplay between retroviruses and innate immunity has emerged as an important component of viral pathogenesis. HIV-1 infection in humans that results in hematologic abnormalities and immune suppression is well represented by changes in the CD4/CD8 T cell ratio and consequent cell death causing CD4 lymphopenia. The innate immune responses by mucosal barriers such as complement, DCs, macrophages, and NK cells as well as cytokine/chemokine profiles attain great importance in acute HIV-1 infection, and thus, prevent mucosal capture and transmission of HIV-1. Conversely, HIV-1 has evolved to overcome innate immune responses through RNA-mediated rapid mutations, pathogen-associated molecular patterns (PAMPs) modification, down-regulation of NK cell activity and complement receptors, resulting in increased secretion of inflammatory factors. Consequently, epithelial tissues lining up female reproductive tract express innate immune sensors including anti-microbial peptides responsible for forming primary barriers and have displayed an effective potent anti-HIV activity during phase I/II clinical trials.

Abnormal Shift in B Memory Cell Profile Is Associated With the Expansion of Circulating T Follicular Helper Cells via ICOS Signaling During Acute HIV-1 Infection

Abnormal Shift in B Memory Cell Profile Is Associated With the Expansion of Circulating T Follicular Helper Cells via ICOS Signaling During Acute HIV-1 Infection

Ethical considerations for HIV remission clinical research involving participants diagnosed during acute HIV infection

Ethical considerations for HIV remission clinical research involving participants diagnosed during acute HIV infection

Острая ВИЧ-инфекция и гиперактивация иммунной системы: клинический случай развития гемофагоцитарного синдрома

Острая ВИЧ-инфекция и гиперактивация иммунной системы: клинический случай развития гемофагоцитарного синдрома

Acute myocardial infarction and HIV infection: A case-based review

Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is a life-threatening condition. Cardiovascular (CV) complications are not uncommon and are one of the leading causes of death in patients suffering from this infection. This case report is of a patient, tested HIV positive who presented to the hospital with myocardial infarction (MI). The objective of this case review is to highlight CV complication such as MI in HIV/AIDS who did not have common cardiac risk factors such as diabetes mellitus, hypertension, or obesity. Acute MI may be presenting feature of HIV infection and may need timely intervention by combined specialist care.

Optimal treatment strategies to control acute HIV infection.

Various antiretroviral therapies (ART) are administered to symptomatic human immunodeficiency virus (HIV) infected individuals to improve their health. The treatment effectiveness may depend on suppressing development of drug resistance, reduce evolution of new viral strains, minimize serious side effects and the costs of drugs. This paper deals with some results concerning optimal drug administration scheme successful in improving patients' health especially in poorly resourced settings. The model under consideration describes the interaction between the uninfected cells, the latently infected cells, the productively infected cells, and the free viruses. Generally, in viral infection, the drug strategy aspects either the virus infectivity or reduce the virion production. The mathematical model proposed here, deals with both situations with the objective function based on a combination of maximizing benefit relied on T cells count (the white cells that coordinate activities of the immune system) and minimizing the systemic cost. The existence of the optimal control pair is established and the Pontryagin's minimum principle is used to characterize these two optimal controls. The optimality system is derived and solved numerically using the forward and backward sweep method (FBSM). Our results indicate that early initiation of treatment makes a profound impact in both improving the quality of life and reducing the economic costs of therapy.

1048. Weight Gain after Initiation of Anti-Retroviral Therapy in Acute HIV-1

BackgroundBackground: Excess weight gain with integrase strand transfer inhibitors (INSTIs) has been reported in some people with chronic HIV. In antiretroviral therapy (ART)-naïve people, greater weight gain over 18 months was reported with dolutegravir than other agents. We hypothesized that initiating an INSTI-based regimen during acute HIV infection (AHI) would result in more weight gain than a non-INSTI-based regimen, and INSTIs other than elvitegravir (EVG) would be associated with greater weight gain than EVG.MethodsMethods: We performed a retrospective, observational, single center chart review analysis of adults with AHI (Feibig Stages 1-5) who were initiated on ART and followed for 48 (+/- 12) weeks. Changes in weight between people on INSTI- vs non-INSTI regimens were compared, and in a subgroup analysis, EVG vs non-EVG and tenofovir alafenamide (TAF) vs non-TAF were compared. Chi-square, t-test, or Wilcoxon Rank Sum test were used, when appropriate.ResultsResults: Baseline characteristics of the 61 participants are shown in Table 1. Overall median (IQR) weight change was 4.53 (1.22-8.36; within-group P< 0.0001) kg (Figure 1). Median weight change in 58 people initiated on INSTI was 4.66 (1.22-8.43; P< 0.0001) kg vs 1.64 (-3.08-6.57; P=0.75) kg in 3 people not on INSTI (between-group P= 0.33). Median weight change on EVG was 4.40 (0.91-6.71; P< 0.0001) kg vs 7.10 (4.97-13.15; P= 0.0001) kg for non-EVG INSTIs (between-group P= 0.008, Figure 2). Median weight change on TAF (n=33) was 2.66 (0.81-7.53; P= 0.002) kg vs 5.31 (3.72-9.34; P < 0.0001) kg in non-TAF (n=25) recipients (between-group P= 0.06). Lower baseline CD4+ T cell count correlated with greater weight gain (P= 0.012). No association between weight gain and race (P= 0.930) or gender (P= 0.379) was noted.Baseline characteristics and median weight change (kg) from baseline Weight change in elvitegravir vs non-elvitegravir integrase inhibitor regimen. Overall weight gain seen over 48 weeks after initiation of antiretroviral therapy calculated using the Wilcoxon Rank Sum test. ConclusionPeople initiating ART during AHI gained weight over 48 weeks, with persons taking INSTIs gaining more weight, though this finding did not reach statistical significance due to small sample size. Amongst INSTI-treated persons, those not on EVG gained more weight than those on EVG. While the benefits of starting ART during AHI on immune system preservation and reservoir should not be underscored, risk and consequences of weight gain following ART initiation should be discussed when initiating ART during AHI.Disclosures Jordan Lake, MD, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator)

LB-6. Increased Diagnoses of Acute HIV Infection through Routine ED Screening and Rapid Linkage to Care and initiation of HAART During the COVID-19 Pandemic

BackgroundThe COVID-19 pandemic has negatively impacted routine HIV screening in healthcare settings. This has serious implications, especially for patients with acute HIV infection (AHI) presenting with symptoms suggesting COVID-19 infection. This is a high priority population for rapid linkage to care (LTC) and initiation of HAART.MethodsWe reviewed data from our eXpanded HIV Testing and LTC (X-TLC) Program, a collaboration effort between 13 healthcare centers on the South and West Sides of Chicago. Since 2016, most sites had 4th or 5th generation HIV Ag/Ab testing available.ResultsMost sites experienced reductions in HIV screens during the COVID-19 pandemic. Advanced planning by our ED incorporated blood draws for HIV screens as part of COVID-19 evaluations. UCM performed 19,111 HIV screens (11,133 in the ED) between 1/1/20 and 8/17/20, along with 100,635 COVID PCRs (14,754 in ED) between 3/17/20 and 8/17/20. Nine patients were diagnosed with AHI after the first case of COVID-19 in Chicago (1/24/20), and 7 were diagnosed after the first case of community transmission in Cook County (3/8/20). All cases of AHI were diagnosed in the ED. The rate of AHI was significantly higher in 2020 versus the prior 4 years (14.4 vs 6.8 per year, p < 0.05). AHI patients comprised 25.7 % (9/35) of all new diagnoses, the highest percent ever. There were 7 men (6 identified as MSM) and 2 cis-gender women, median age of 25 years (21 to 28 years). The median viral load was 6 million (115,000 to > 6 million) copies/mL. Eight of 9 patients presented with an illness indistinguishable from COVID-19, including 1co-infected patient. All were LTC and started on HAART from time of PCR result within a median of 1 day (0–38), but 3 days (range 1–41) from sample collection as a result of delayed reflex PCR confirmatory testing due to high demands on lab personnel and scarcity of reagents due to COVID-19 PCR volumes (since resolved).HIV Screening and COVID-19 Testing in the ED During COVID-19 ConclusionContinued HIV screening in our ED during the COVID-19 pandemic identified an increased number of patients with AHI. These individuals may be more likely to present for care due to fear of COVID-19 infection. We achieved rapid LTC and initiation of HAART without any incremental increases in resources. All HIV screening programs should incorporate blood-based HIV screening into their COVID-19 testing programs.Disclosures Moira McNulty, MD, MS, Gilead Sciences (Grant/Research Support)

Novel Criteria for Diagnosing Acute and Early Human Immunodeficiency Virus Infection in a Multinational Study of Early Antiretroviral Therapy Initiation.

Antiretroviral therapy (ART) initiation during acute and early human immunodeficiency virus infection (AEHI) limits HIV reservoir formation and may facilitate post-ART control but is logistically challenging. We evaluated the performance of AEHI diagnostic criteria from a prospective study of early ART initiation. AIDS Clinical Trials Group A 5354 enrolled adults at 30 sites in the Americas, Africa, and Asia who met any 1 of 6 criteria based on combinations of results of HIV RNA, HIV antibody, Western blot or Geenius assay, and/or the signal-to-cutoff (S/CO) ratio of the ARCHITECT HIV Ag/Ab Combo or GS HIV Combo Ag/Ab EIA. HIV status and Fiebig stage were confirmed by centralized testing. From 2017 through 2019, 195 participants were enrolled with median age of 27 years (interquartile range, 23-39). Thirty (15.4%) were female. ART was started by 171 (87.7%) on the day of enrollment and 24 (12.3%) the next day. AEHI was confirmed in 188 (96.4%) participants after centralized testing, 4 (2.0%) participants were found to have chronic infection, and 3 (1.5%) found not to have HIV discontinued ART and were withdrawn. Retrospectively, a nonreactive or indeterminate HIV antibody on the Geenius assay combined with ARCHITECT S/CO ≥10 correctly identified 99 of 122 (81.2%) Fiebig II-IV AEHI cases with no false-positive results. Novel AEHI criteria that incorporate ARCHITECT S/CO facilitated rapid and efficient ART initiation without waiting for an HIV RNA result. These criteria may facilitate AEHI diagnosis, staging, and immediate ART initiation in future research studies and clinical practice. NCT02859558.

968. The Impact of Opt-Out HIV Screening and Patient Navigator-Assisted Linkage to Care of Newly Diagnosed Persons with HIV in a High-Prevalence Emergency Department

BackgroundNewark is the epicenter of the HIV epidemic in New Jersey. University Hospital, the state’s only public safety net hospital, plays a critical role in identifying and linking newly diagnosed persons with HIV (PWH) to care. We previously showed that the emergency department (ED) is the most common setting for missed testing opportunities. Therefore, in 2015 we implemented a routine opt-out HIV screening and patient navigator (PN)-assisted linkage to care (LTC) protocol in the ED, and this project examined the LTC rates for newly diagnosed PWH.MethodsWe conducted an IRB-approved retrospective chart review of patients who tested positive for HIV in the ED between 2015 and 2018. Descriptive statistics were used to summarize demographic and clinical data. Univariate and multivariate regression were used to identify demographic and clinical factors associated with LTC for newly diagnosed PWH. Age, sex, and factors with p ≤ 0.10 in the univariate analysis were included in the final model.ResultsOf the 464 patients who screened positive, 123 (26.5%) were new diagnoses. The mean age was 41.0 years (SD = 13.8); 82 (67%) male; 74 (60%) black, 26 (21%) Hispanic, 7 (6%) white. The median CD4 count was 242 (IQR = 120 - 478) cells/µL, and 10 patients (8.1%) had acute HIV infection. Six patients (4.9%) died before LTC. Among the remaining 117 patients, PN outreach resulted in scheduled appointments at the Infectious Disease Practice for 102 (87.2%). In total, 79 (67.5%) were linked to care and 38 (32.5%) were referred to the state for linkage. Of the patients linked to care, 49 (62.0%) attended their first appointment and 30 (38.0%) required additional PN outreach. Men who have sex with men (MSM) (OR = 17.2, p = 0.002) and heterosexual contact (OR = 6.3, p < 0.001) were predictive of LTC.ConclusionOur protocol resulted in LTC for the majority of newly diagnosed PWH. Among those linked to care, over a third required additional PN outreach after missing their first appointment, highlighting the importance of PN follow-up. MSM and heterosexual contact, the two highest risk factors for HIV in New Jersey, were predictive of LTC. Their successful LTC may be explained, in part, by the fact that PNs were demographically similar and lessened perceived stigma associated with entry into care.Disclosures All Authors: No reported disclosures

Integrase Strand Transfer Inhibitors Play the Main Role in Greater Weight Gain Among Men With Acute and Early HIV Infection.

BackgroundThe predictors of weight gain remain unclear in people with acute and early HIV infection (AEH).MethodsEligible antiretroviral-naïve men diagnosed with AEH from January 1, 2000, to December 31, 2019, were enrolled in an observational cohort study at the University California, San Diego. The study used multivariable mixed-effect linear regression models to analyze differences in the rate of weight gain over time between participants receiving early vs deferred antiretroviral therapy (ART) treatment, low vs high baseline CD4 count and HIV RNA, and different classes of ART.ResultsA total of 463 participants were identified, with mean CD4 cell count of 507 cells/μL and log HIV RNA of 5.0 copies/mL at study entry. There was no difference in the rate of weight gain between participants who did and did not receive ART within 96 weeks of incident HIV infection. Neither a baseline CD4 count of <350 cells/μL nor a baseline HIV RNA of >100 000 copies/mL was a predictor of weight gain. Compared with persons taking non-nucleoside reverse transcriptase inhibitor–based regimens, those who received integrase strand transfer inhibitor (INSTI)–based regimens showed greater weight gain over time.ConclusionsNeither baseline CD4 count and HIV RNA nor early ART was associated with weight change in the first 96 weeks following incident HIV infection. Use of INSTI-based regimens represented a major driver of weight gain in men who initiated ART with relatively higher CD4 cell counts.

HIV as A Cause of Acute Liver Injury

While hepatitis is the most common infectious cause of acute liver injury, although rare, acute human immunodeficiency virus (HIV) infection should be considered in the workup for infectious causes of acute liver injury. We present a case of a 36 year old woman with no past medical history who presented to the hospital for 8 days of abdominal pain and nausea worsened with food. Labs were significant for lymphocytopenia, transaminitis, elevated alkaline phosphatase, and direct bilirubinemia. Viral hepatitis serologies were negative and imaging showed nonspecific gallbladder wall thickening, no gallbladder stones, no intra or extra-hepatic biliary ductal dilatation. No evidence of congestive heart failure. Serologies for cytomegalovirus (CMV), Epstein Barr virus (EBV), rickettsia, enterovirus, adenovirus, and parvovirus were negative. Workup for autoimmune liver disease was also negative. Liver biopsy was notable for a focus of granulomatous necrosis, suggestive of infectious or drug induced etiology. During this admission, patient was also found to have a new diagnosis of HIV with CD4 count of 235. Patient was started on bictegravir, emtricitabine, and tenofovir alafenamide with progressive improvement and eventual resolution of AST, ALT, alkaline phosphatase, and bilirubin elevation since starting anti-retroviral therapy.*++

Loss of memory B cells impairs maintenance of long-term serologic memory during HIV-1 infection

Circulating memory B cells are severely reduced in the peripheral blood of HIV-1-infected patients. We investigated whether dysfunctional serologic memory to non-HIV antigens is related to disease progression by evaluating the frequency of memory B cells, plasma IgG, plasma levels of antibodies to measles, and Streptococcus pneumoniae, and enumerating measles-specific antibody-secreting cells in patients with primary, chronic, and long-term nonprogressive HIV-1 infection. We also evaluated the in vitro production of IgM and IgG antibodies against measles and S pneumoniae antigens following polyclonal activation of peripheral blood mononuclear cells (PBMCs) from patients. The percentage of memory B cells correlated with CD4+ T-cell counts in patients, thus representing a marker of disease progression. While patients with primary and chronic infection had severe defects in serologic memory, long-term nonprogressors had memory B-cell frequency and levels of antigen-specific antibodies comparable with controls. We also evaluated the effect of antiretroviral therapy on these serologic memory defects and found that antiretroviral therapy did not restore serologic memory in primary or in chronic infection. We suggest that HIV infection impairs maintenance of long-term serologic immunity to HIV-1-unrelated antigens and this defect is initiated early in infection. This may have important consequences for the response of HIV-infected patients to immunizations.

Human immunodeficiency virus–related peripheral neuropathy: A systematic review and meta‐analysis

Human immunodeficiency virus (HIV)-associated neurological syndromes occur in affected individuals as a consequence of primary HIV infection, opportunistic infections, inflammation and as an adverse effect of some forms of antiretroviral treatment (ART). The aim of this systematic review was to establish the epidemiological characteristics, clinical features, pathogenetic mechanisms and risk factors of HIV-related peripheral neuropathy (PN). A systematic, computer-based search was conducted using the PubMed database. Data regarding the above parameters were extracted. Ninety-four articles were included in this review. The most commonly described clinical presentation of HIV neuropathy is the distal predominantly sensory polyneuropathy. The primary pathology in HIVPN appears to be axonal rather than demyelinating. Age and treatment with medications belonging in the nucleoside analogue reverse transcriptase class are risk factors for developing HIV-related neuropathy. The pooled prevalence of PN in patients naïve to ARTs was established to be 29% (95% CI: 9%-62%) and increased to 38% (95% confidence interval [CI]: 29%-48%) when looking into patients at various stages of their disease. More than half of patients with HIV-related neuropathy are symptomatic (53%, 95% CI: 41%-63%). Management of HIV-related neuropathy is mainly symptomatic, although there is evidence that discontinuation of some types of ART, such as didanosine, can improve or resolve symptoms. Human immunodeficiency virus-related neuropathy is common and represents a significant burden in patients' lives. Our understanding of the disease has grown over the last years, but there are unexplored areas requiring further study.

Longitudinal Analysis of Peripheral and Colonic CD161+ CD4+ T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation.

CD161 expression on CD4+ T cells is associated with a Th17 functional phenotype, as well as with an innate capacity to respond to interleukin (IL)-12 and IL-18 without T cell receptor (TCR) stimulation. Chronic HIV-1 infection is associated with loss of the CD161+ CD4 T cell population, and non-human primate studies suggest that their depletion is associated with disease progression. However, the dynamics of the CD161+ CD4+ T cell population during acute HIV-1 infection remains unknown. In this study, we characterize peripheral blood CD161+ CD4+ T cells in detail, and examine how they are affected during the earliest stages of HIV-1 infection. Unbiased surface proteome screening and principal component analysis indicated that CD161+ CD4+ T cells are relatively phenotypically homogeneous between donors, and are intermediates between conventional CD4 T cells and innate-like T cells. In acute untreated HIV-1 infection, the circulating CD161+ CD4+ T cell population decreased in frequency, as did absolute cell counts starting from peak viral load, with elevated levels of activation and exhaustion markers expressed throughout acute HIV-1 infection. The capacity of these cells to respond to stimulation with IL-12 and IL-18 was also reduced. Early initiation of anti-retroviral treatment (ART) during acute HIV-1 infection restored the functionality of peripheral blood CD161+ CD4+ T cells, but not their frequency. In contrast, early ART initiation prevented the decline of colonic CD161+ CD4+ T cells that otherwise started during acute infection. Furthermore, loss of peripheral and colonic CD161+ CD4+ T cells in untreated infection was associated with levels of viral load. These results suggest that acute HIV-1 infection has profound effects on the CD161+ CD4+ T cell population that could not be completely prevented by the initiation of ART.

Minimal detection of cerebrospinal fluid escape after initiation of antiretroviral therapy in acute HIV-1 infection.

Despite suppression of HIV-1 replication in the periphery by antiretroviral therapy (ART), up to 10% of treated individuals have quantifiable HIV-1 in the CSF, termed CSF escape. CSF escape may be asymptomatic but has also been linked to progressive neurological disease, and may indicate persistence of HIV in the central nervous system (CNS). CSF escape has not yet been assessed after initiation of ART during acute HIV-1 infection (AHI). Prospective cohort study. Major voluntary counseling and testing site in Bangkok, Thailand. Participants identified and initiated on ART during AHI who received an optional study lumbar puncture at pre-ART baseline or after 24 or 96 weeks of ART. Paired levels of CSF and plasma HIV-1 RNA, with CSF greater than plasma HIV-1 RNA defined as CSF escape. Two hundred and four participants had paired blood and CSF sampling in at least one visit at baseline, week 24, or week 96. Twenty-nine participants had CSF sampling at all three visits. CSF escape was detected in 1/90 at week 24 (CSF HIV-1 RNA 2.50 log10 copies/ml, plasma HIV-1 RNA <50 copies/ml), and 0/55 at week 96. Although levels of CSF HIV-1 RNA in untreated AHI are high, initiating treatment during AHI results in a very low rate of CSF escape in the first 2 years of treatment. Early treatment may improve control of HIV-1 within the CNS compared with treatment during chronic infection, which may have implications for long-term neurological outcomes and CNS HIV-1 persistence.

The V2 loop of HIV gp120 delivers costimulatory signals to CD4+ T cells through Integrin α4β7 and promotes cellular activation and infection

Acute HIV infection is characterized by rapid viral seeding of immunologic inductive sites in the gut followed by the severe depletion of gut CD4+ T cells. Trafficking of α4β7-expressing lymphocytes to the gut is mediated by MAdCAM, the natural ligand of α4β7 that is expressed on gut endothelial cells. MAdCAM signaling through α4β7 costimulates CD4+ T cells and promotes HIV replication. Similar to MAdCAM, the V2 domain of the gp120 HIV envelope protein binds to α4β7 In this study, we report that gp120 V2 shares with MAdCAM the capacity to signal through α4β7 resulting in CD4+ T cell activation and proliferation. As with MAdCAM-mediated costimulation, cellular activation induced by gp120 V2 is inhibited by anti-α4β7 monoclonal antibodies (mAbs). It is also inhibited by anti-V2 domain antibodies including nonneutralizing mAbs that recognize an epitope in V2 that has been linked to reduced risk of acquisition in the RV144 vaccine trial. The capacity of the V2 domain of gp120 to mediate signaling through α4β7 likely impacts early events in HIV infection. The capacity of nonneutralizing V2 antibodies to block this activity reveals a previously unrecognized mechanism whereby such antibodies might impact HIV transmission and pathogenesis.