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Productively infected cells are generally thought to arise from HIV infection of activated [CD4.sup.+] T cells, and these infected activated cells are thought to be a recurring source of latently infected cells when a portion of the population transitions to a resting state. We discovered and report here that productively and latently infected cells can instead originate from direct infection of resting [CD4.sup.+] T cell populations in lymphoid tissues in Fiebig I, the earliest stage of detectable HIV infection. We found that direct infection of resting [CD4.sup.+] T cells was correlated with the availability of susceptible target cells in lymphoid tissues largely restricted to resting [CD4.sup.+] T cells in which expression of pTEFb enabled productive infection, and we documented persistence of HIV-producing resting T cells during antiretroviral therapy (ART). Thus, we provide evidence of a mechanism by which direct infection of resting T cells in lymphoid tissues to generate productively and latently infected cells creates a mechanism by which the productively infected cells can replenish both populations and maintain two sources of virus from which HIV infection can rebound, even if ART is instituted at the earliest stage of detectable infection., Introduction From the beginning of HIV research, HIV has been mainly propagated in vitro in tissue cultures of activated [CD4.sup.+] T cells (1), leading to the prevailing view that activated [...]

IntroductionLiver disease is a common cause of non-AIDS morbidity and mortality in people living with HIV (PLHIV), but the prevalence and significance of liver function test (LFT) abnormalities in early HIV infection is unknown. This study aimed to characterize LFTs in a large cohort of participants with acute HIV infection initiating immediate antiretroviral therapy (ART) and examine the association between LFTs and biomarkers of HIV infection and inflammation.MethodsWe measured LFTs at the time of HIV diagnosis and at 4, 12, 24 and 48 weeks after ART initiation in 426 Thai individuals with acute HIV infection from 2009 to 2018. A subset of individuals had data available at 96 and 144 weeks. We excluded individuals with concomitant viral hepatitis. Alanine aminotransferase (ALT) was the primary outcome of interest; values greater than 1.25 times the upper limit of normal were considered elevated. Analyses utilized descriptive statistics, non-parametric tests and multivariate logistic regression.ResultsSixty-six of the 426 individuals (15.5%) had abnormal baseline ALT levels; the majority (43/66, 65.5%) had Grade 1 elevations. Elevated baseline ALT correlated with Fiebig stages III to V (p = 0.001) and baseline HIV RNA >6 log10 copies/mL (p = 0.012). Baseline elevations resolved by 48 weeks on ART in 59 of the 66 individuals (89%). ALT elevations at 24 and 48 weeks correlated with Fiebig stages I to II at diagnosis (p 350 cells/μL (p = 0.03) and older age (p = 0.03). Individuals initiating efavirenz-based regimens were more likely to have elevated ALT levels at 48 weeks compared with those on non-efavirenz-based regimens (p = 0.003).ConclusionsOne in six people with acute HIV infection have elevated LFTs. Clinical outcomes with ART started in acute HIV are generally good, with resolution of ALT elevations within 48 weeks on ART in most cases. These results suggest a multifactorial model for hepatic injury involving a combination of HIV-associated and ART-associated processes, which may change over time.

BackgroundChronic immune activation in the blood and central nervous system is a consequence of human immunodeficiency virus (HIV) infection that contributes to disease morbidity and can occur despite virally suppressive antiretroviral therapy (ART). The trajectory of HIV-related inflammation may vary with the timing of ART initiation. We examined immune activation markers in cerebrospinal fluid (CSF) and blood specimens collected over 96 weeks from participants who initiated ART during acute HIV infection (AHI).MethodsRV254/SEARCH010 study participants with AHI underwent CSF (n = 89) and plasma (n = 146) sampling before initiating ART and at weeks 24 and 96 of treatment. A majority participants (64.4%) received a standard ART regimen (hereafter, "standard ART"), with some (34.7%) also receiving maraviroc and raltegravir for the first 24 weeks (hereafter, "ART plus"). We compared neopterin, CXCL10, CCL2, and interleukin 6 (IL-6) levels in the AHI group to those in 18 healthy, uninfected controls.ResultsFollowing 24 and 96 weeks of treatment, levels of all CSF markers normalized while levels of several plasma markers remained elevated in the AHI group (P < .001). Participants receiving the ART-plus regimen had lower median plasma CCL2 levels at week 24 and lower plasma neopterin levels at week 96.ConclusionsART initiation during AHI differentially impacts the brain compartment, with markers of inflammation returning to normal levels in the CSF, where they were sustained at week 96, but not in plasma.

This observational study of 123 Thai participants sought to determine the rate and severity of affective symptoms during acute HIV infection (AHI) and possible associations to disease mechanisms. At diagnosis, just prior to starting combination antiretroviral therapy (cART), AHI participants completed assessments of depression and anxiety symptoms that were repeated at 4, 12, and 24 weeks. Blood markers of HIV infection and immune activation were measured at study entry, with optional cerebrospinal fluid measures. A high frequency of participants reported symptoms that exceeded published thresholds supportive of depression (55.0%) and anxiety (65.8%) at diagnosis, with significant reductions after starting cART. Meeting a threshold for clinically relevant depressive symptoms at study entry was associated with higher baseline plasma HIV RNA (5.98 vs. 5.50, t = 2.46, p = 0.015), lower CD4 counts (328 vs. 436 cells/mm3, t = 3.46, p = 0.001), and higher plasma neopterin, a marker of macrophage activation (2694 vs. 1730 pg/mL, Mann-Whitney U = 152.5, p = 0.011). Controlling for plasma HIV RNA and CD4 count, higher baseline plasma neopterin correlated with worse initial depression and anxiety scores. Depression and anxiety symptoms are frequent in acute HIV infection, associate with plasma immune activation, and can improve concurrent with cART.

ObjectiveTo determine the incidence, timing, and severity of neurologic findings in acute HIV infection (pre-antibody seroconversion), as well as persistence with combination antiretroviral therapy (cART).MethodsParticipants identified with acute HIV were enrolled, underwent structured neurologic evaluations, immediately initiated cART, and were followed with neurologic evaluations at 4 and 12 weeks. Concurrent brain MRIs and both viral and inflammatory markers in plasma and CSF were obtained.ResultsMedian estimated HIV infection duration was 19 days (range 3-56) at study entry for the 139 participants evaluated. Seventy-three participants (53%) experienced one or more neurologic findings in the 12 weeks after diagnosis, with one developing a fulminant neurologic manifestation (Guillain-Barré syndrome). A total of 245 neurologic findings were noted, reflecting cognitive symptoms (33%), motor findings (34%), and neuropathy (11%). Nearly half of the neurologic findings (n = 121, 49%) occurred at diagnosis, prior to cART initiation, and most of these (n = 110, 90%) remitted concurrent with 1 month on treatment. Only 9% of neurologic findings (n = 22) persisted at 24 weeks on cART. Nearly all neurologic findings (n = 236, 96%) were categorized as mild in severity. No structural neuroimaging abnormalities were observed. Participants with neurologic findings had a higher mean plasma log10 HIV RNA at diagnosis compared to those without neurologic findings (5.9 vs 5.4; p = 0.006).ConclusionsAcute HIV infection is commonly associated with mild neurologic findings that largely remit while on treatment, and may be mediated by direct viral factors. Severe neurologic manifestations are infrequent in treated acute HIV.

Introduction: Up to 30% of individuals treated with antiretroviral therapy (ART) during chronic HIV fail to recover CD4 counts to >500 cells/[mm.sup.3] despite plasma viral suppression. We investigated the frequency and associations of suboptima CD4 recovery after ART started during acute HIV infection (AHI). Methods: Participants who started ART in Fiebig I to V AHI with [greater than or equal to]48 weeks of continuous documented HIV-RNA< 50 copies/mL were stratified by CD4 count at latest study visit to suboptimal immune recovery (SIR; CD4 < 350 cells/[mm.sup.3]), intermediate immune recovery (IIR; 350 [less than or equal to] CD4 < 500) and complete immune recovery (CIR; CD4 [greater than or equal to] 500). Clinical and laboratory parameters were assessed at pre-ART baseline and latest study visit. Additional inflammatory and neurobehavioral end-points were examined at baseline and 96 weeks. Results: Of 304 participants (96% male, median 26 years old) evaluated after median 144 (range 60 to 420) weeks of ART initiated at median 19 days (range 1 to 62) post-exposure, 3.6% (n = 11) had SIR and 14.5% (n = 44) had IIR. Pre-ART CD4 count in SIR compared to CIR participants was 265 versus 411 cells/[mm.sup.3] (p = 0.002). Individuals with SIR or IIR had a slower CD4 rate of recovery compared to those with CIR. Timing of ART initiation by Fiebig stage did not affect CD4 count during treatment. Following ART, the [CD8.sup.+]T cell count (p = 0.001) and CD4/CD8 ratio (p = 0.047) were lower in SIR compared to CIR participants. Compared to the CIR group at week 96, the combined SIR and IIR groups had higher sCD14 (p = 0.008) and lower IL-6 (p = 0.04) in plasma, without differences in neuropsychological or psychiatric indices. Conclusions: Despite immediate and sustained treatment in AHI, suboptimal CD4 recovery occurs uncommonly and is associated with low pre-ART CD4 count as well as persistent low CD8 count and CD4/CD8 ratio during treatment. Keywords: ARV; Asia; men who have sex with men; LMIC; immunology; HIV care continuum Additional information may be found under the Supporting Information tab for this article., 1 | INTRODUCTION In the era of potent antiretroviral therapy (ART), ongoing HIV replication is adequately suppressed to undetectable levels in appropriately treated individuals. However, up to 30% of ART-treated [...]

Early initiation of antiretroviral therapy (ART) in acute HIV infection (AHI) is effective at limiting seeding of the HIV viral reservoir, but little is known about how the resultant decreased antigen load affects long-term Ab development after ART. We report here that Env-specific plasma antibody (Ab) levels and Ab-dependent cellular cytotoxicity (ADCC) increased during the first 24 weeks of ART and correlated with Ab levels persisting after 48 weeks of ART. Participants treated in AHI stage 1 had lower Env-specific Ab levels and ADCC activity on ART than did those treated later. Importantly, participants who initiated ART after peak viremia in AHI developed elevated cross-clade ADCC responses that were detectable 1 year after ART initiation, even though clinically undetectable viremia was reached by 24 weeks. These data suggest that there is more germinal center (GC) activity in the later stages of AHI and that Ab development continues in the absence of detectable viremia during the first year of suppressive ART. The development of therapeutic interventions that can enhance earlier development of GCs in AHI and Abs after ART initiation could provide important protection against the viral reservoir that is seeded in individuals treated early in the disease., Introduction Initiation of antiretroviral therapy (ART) during acute HIV infection (AHI) is associated with multiple benefits, including decreased HIV reservoir size (1-6) and preservation of a homogenous viral reservoir with [...]

: Introduction: Dolutegravir (DTG) is recommended as part of first‐line antiretroviral therapy (ART) for people living with HIV(PLHIV). We sought to determine the rate of adverse events (AEs) and discontinuations among Thais treated during acute HIV infection (AHI) and switched to DTG‐based regimens. Methods: Thai participants in the SEARCH010/RV254 cohort who initiated ART during AHI and switched to DTG for at least 48 weeks were prospectively observed and included in the analysis. Rates and characteristics of DTG‐related AEs and discontinuations were described. Results: A total of 313 Thai participants were included in the analysis. The median age was 29 years, 96% were male, 64% had a Bachelor's degree or higher and 16% had a body mass index (BMI) Conclusions: DTG was well tolerated with few discontinuations in this cohort of young men. Incident hepatitis C virus infection was a driver of liver‐related AEs leading to discontinuations. In populations at risk, regular testing for hepatitis C virus during ART is recommended to anticipate possible AEs, guide management and improve safety., Introduction Dolutegravir (DTG) is a potent second generation HIV integrase strand transfer inhibitor (INSTI) with a favourable profile of efficacy, safety and tolerability in adults and adolescents. It has a [...]

Starting antiretroviral therapy (ART) in Fiebig 1 acute HIV infection limits the size of viral reservoirs in lymphoid tissues, but does not impact time to virus rebound during a treatment interruption. To better understand why the reduced reservoir size did not increase the time to rebound we measured the frequency and location of HIV RNA+ cells in lymph nodes from participants in the RV254 acute infection cohort. HIV RNA+ cells were detected more frequently and in greater numbers when ART was initiated in Fiebig 1 compared to later Fiebig stages and were localized to the T-cell zone compared to the B-cell follicle with treatment in later Fiebig stages. Variability of virus production in people treated during acute infection suggests that the balance between virus-producing cells and the immune response to clear infected cells rapidly evolves during the earliest stages of infection. Clinical Trials Registration: NCT02919306. [ABSTRACT FROM AUTHOR]

Introduction: Up to 30% of individuals treated with antiretroviral therapy (ART) during chronic HIV fail to recover CD4 counts to >500 cells/mm3 despite plasma viral suppression. We investigated the frequency and associations of suboptimal CD4 recovery after ART started during acute HIV infection (AHI). Methods: Participants who started ART in Fiebig I to V AHI with ≥48 weeks of continuous documented HIV‐RNA < 50 copies/mL were stratified by CD4 count at latest study visit to suboptimal immune recovery (SIR; CD4 < 350 cells/mm3), intermediate immune recovery (IIR; 350 ≤ CD4 < 500) and complete immune recovery (CIR; CD4 ≥ 500). Clinical and laboratory parameters were assessed at pre‐ART baseline and latest study visit. Additional inflammatory and neurobehavioral endpoints were examined at baseline and 96 weeks. Results: Of 304 participants (96% male, median 26 years old) evaluated after median 144 (range 60 to 420) weeks of ART initiated at median 19 days (range 1 to 62) post‐exposure, 3.6% (n = 11) had SIR and 14.5% (n = 44) had IIR. Pre‐ART CD4 count in SIR compared to CIR participants was 265 versus 411 cells/mm3 (p = 0.002). Individuals with SIR or IIR had a slower CD4 rate of recovery compared to those with CIR. Timing of ART initiation by Fiebig stage did not affect CD4 count during treatment. Following ART, the CD8+T cell count (p = 0.001) and CD4/CD8 ratio (p = 0.047) were lower in SIR compared to CIR participants. Compared to the CIR group at week 96, the combined SIR and IIR groups had higher sCD14 (p = 0.008) and lower IL‐6 (p = 0.04) in plasma, without differences in neuropsychological or psychiatric indices. Conclusions: Despite immediate and sustained treatment in AHI, suboptimal CD4 recovery occurs uncommonly and is associated with low pre‐ART CD4 count as well as persistent low CD8 count and CD4/CD8 ratio during treatment. [ABSTRACT FROM AUTHOR]

Introduction: Dolutegravir (DTG)-based antiretroviral therapy (ART) is currently the first-line treatment for people living with HIV. Neuropsychiatric adverse events (NP-AEs) have been reported with DTG but neuropsychiatric symptoms have not been systemically quantified using structured scales. This study examined mood and cognitive parameters before and after a planned transition from non-DTG to DTG-based ART within a longitudinal study of acute HIV infection (AHI). Methods: RV254 AHI cohort participants on ≥ 24 weeks of ART initiated at AHI underwent sequential assessments before and after the switch including: (1) Patient Health Questionnaire-9 (PHQ-9), a 9-item survey (scores 0–27) that evaluates somatic and affective/cognitive symptoms of depression; (2) a 2-Questions screening that has been validated locally for depression; (3) Distress Thermometer (scores 0–10); and 4) administration of a 4-test neurocognitive battery sensitive to HIV. Results: 254 individuals (95% male, median age 30) switched to a DTG-based regimen after a median 144 weeks of ART. Serial assessments were completed at a median of 19 weeks before and 37 weeks after DTG. There was a modest but statistically significant increase in PHQ-9 scores after DTG (pre-switch: 5 [IQR 1–7] vs. Post-switch: 5 [IQR 2–8], p = 0.009). The percentage of participants with at least moderate depression (PHQ-9 ≥ 10) increased from 10 to 16% (p = 0.006), but the frequency of moderate-severe depression (PHQ-9 ≥ 15) remained unchanged (3%). No volunteer reported NP-AEs within the study period. Somatic symptoms of depression increased more than cognitive/affective symptoms. Plasma viral suppression (HIV-1 RNA < 50; p = 0.005) and PHQ-9 ≥ 10 (p < 0.001) before switch were linked to lower PHQ-9 scores after DTG in multivariable analysis. Performance on all neuropsychological tests, except grooved pegboard test, improved modestly after DTG (all p < 0.05). Conclusion: After a median duration of 37 weeks of DTG use, there was a modest increase in the higher quartile of PHQ-9. This increase was associated with a rise in moderate depression symptoms but not the more severe forms of depression on PHQ-9. No clinically relevant NP-AEs were reported. Pre-existing depression was not associated with subsequent worsening of symptoms after DTG. Cognitive test performance improved post-DTG but could be due to practice effect. [ABSTRACT FROM AUTHOR]

HIV-associated neurocognitive disorder (HAND) remains a challenge despite antiretroviral therapy (ART), and has been linked to monocyte/macrophage (M/M) migration to the brain. Due to the potential impact of T cell effector mechanisms in eliminating activated/HIV-infected M/M, T cell activation may play a role in the development of HAND. We sought to investigate the relationship between cognition and both CD8+ T cell activation (HLA-DR+/CD38+) and HIV-specific CD8+ T cell responses at the time of HIV diagnosis and 12 months postinitiation of ART. CD8+ T cell activation was increased in HAND compared to cognitive normal (NL) individuals and correlated directly with plasma viral load and inversely with the cognitive status. In addition, Gag-specific cytolytic activity (CD107a/b+) was decreased in HAND compared with NL individuals and correlated with their neurological testing, suggesting a potential role of cytotoxic CD8+ T cells in the mechanism of HAND development. [ABSTRACT FROM AUTHOR]

Objective: To compare central nervous system (CNS) outcomes in participants treated during acute HIV infection with standard combination antiretroviral therapy (cART) vs. cART plus integrase inhibitor and CCR5 antagonist (cART+). Design: 24-week randomized open-label prospective evaluation. Method: Participants were evaluated then randomized to initiate cART (efavirenz, tenofovir, and either emtricitabine or lamivudine) vs. cART+ (cART plus raltegravir and maraviroc) during acute HIV and re-evaluated at 4, 12 and 24 weeks. We examined plasma and CSF cytokines, HIV RNA levels, neurological and neuropsychological findings, and brain MRS across groups and compared to healthy controls. Results: At baseline, 62 participants were in Fiebig stages I-V. Randomized groups were similar for mean age (27 vs. 25, p = 0.137), gender (each 94% male), plasma log10 HIV RNA (5.4 vs. 5.6, p = 0.382), CSF log10 HIV RNA (2.35 vs. 3.31, p = 0.561), and estimated duration of HIV (18 vs. 17 days, p = 0.546). Randomized arms did not differ at 24 weeks by any CNS outcome. Combining arms, all measures concurrent with antiretroviral treatment improved, for example, neuropsychological testing (mean NPZ-4 of -0.408 vs. 0.245, p<0.001) and inflammatory markers by MRS (e.g. mean frontal white matter (FWM) choline of 2.92 vs. 2.84, p = 0.045) at baseline and week 24, respectively. Plasma neopterin (p<0.001) and interferon gamma-induced protein 10 (IP-10) (p = 0.007) remained elevated in participants compared to controls but no statistically significant differences were seen in CSF cytokines compared to controls, despite individual variability among the HIV-infected group. Conclusions: A 24-week course of cART+ improved CNS related outcomes, but was not associated with measurable differences compared to standard cART. [ABSTRACT FROM AUTHOR]

HIV-1 disseminates to a broad range of tissue compartments during acute HIV-1 infection (AHI). The central nervous system (CNS) can serve as an early and persistent site of viral replication, which poses a potential challenge for HIV-1 remission strategies that target the HIV reservoir. CNS compartmentalization is a key feature of HIV-1 neuropathogenesis. Thus far, the timing of how early CNS compartmentalization develops after infection is unknown. We examined whether HIV-1 transmitted/founder (T/F) viruses differ between CNS and blood during AHI using single-genome sequencing of envelope gene and further examined subregions in pol and env using next-generation sequencing in paired plasma and cerebrospinal fluid (CSF) from 18 individuals. Different proportions of mostly minor variants were found in six of the eight multiple T/F-infected individuals, indicating enrichment of some variants in CSF that may lead to significant compartmentalization in the later stages of infection. This study provides evidence for the first time that HIV-1 compartmentalization in the CNS can occur within days of HIV-1 exposure in multiple T/F infections. Further understanding of factors that determine enrichment of T/F variants in the CNS, as well as potential long-term implications of these findings for persistence of HIV-1 reservoirs and neurological impairment in HIV, is needed. [ABSTRACT FROM AUTHOR]

Clinical research regularly includes required, nontherapeutic procedures to answer research questions. Optional procedures usually offer minimal or no personal benefit and may involve harms and burdens. Members from the Bangkok SEARCH010/RV254 HIV research cohort of individuals acutely HIV-infected are recruited to six optional procedures varying in invasiveness: leukapheresis, genital secretions collection, lumbar puncture, brain MRI/MRS/DTI, colon biopsy, and lymph node biopsy. We surveyed cohort members about their first recruitment for each procedure to examine factors associated with decision making and attitudes about compensation. 406 members (68%) completed the survey. Reported procedure participation ranged from 71% (MRI) to 27% (lymph node biopsy). Respondents underwent 0-6 procedure types (median 3). Ordinal regression indicated that lower perceived HIV impact and HIV remission trial participation were associated with more procedures completed. Reports of decision difficulty varied, and feeling pressured by research staff was low overall. Notably, those who declined procedures and those who underwent more invasive procedures reported greater decision difficulty and perceived pressure. Most respondents felt compensation amounts were appropriate, although opinions differed by procedure, and for some procedures, between people who agreed and declined. There is limited literature regarding consent to and attitudes about optional research procedures. Researchers must consider how to best support voluntary decisions for procedures with little personal benefit, particularly in lower-income or marginalized populations. In this longitudinal research cohort, perceived pressure to participate may be a concern, although our finding of variation in participation rates corresponding to invasiveness is reassuring. Data from different research contexts would provide important comparators., (© 2022 The Authors.)

Background: Harnessing CD8 + T cell responses is being explored to achieve HIV remission. Although HIV-specific CD8 + T cells become dysfunctional without treatment, antiretroviral therapy (ART) partially restores their function. However, the extent of this recovery under long-term ART is less understood., Methods: We analyzed the differentiation status and function of HIV-specific CD8 + T cells after long-term ART initiated in acute or chronic HIV infection ex vivo and upon in vitro recall., Findings: ART initiation in any stage of acute HIV infection promoted the persistence of long-lived HIV-specific CD8 + T cells with high expansion (P<0·0008) and cytotoxic capacity (P=0·02) after in vitro recall, albeit at low cell number (P=0·003). This superior expansion capacity correlated with stemness (r=0·90, P=0·006), measured by TCF-1 expression, similar to functional HIV-specific CD8 + T cells found in spontaneous controllers. Importanly, TCF-1 expression in these cells was associated with longer time to viral rebound ranging from 13 to 48 days after ART interruption (r =0·71, P=0·03). In contrast, ART initiation in chronic HIV infection led to more differentiated HIV-specific CD8 + T cells lacking stemness properties and exhibiting residual dysfunction upon recall, with reduced proliferation and cytolytic activity., Interpretation: ART initiation in acute HIV infection preserves functional HIV-specific CD8 + T cells, albeit at numbers too low to control viral rebound post-ART. HIV remission strategies may need to boost HIV-specific CD8 + T cell numbers and induce stem cell-like properties to reverse the residual dysfunction persisting on ART in people treated after acute infection prior to ART release., Funding: U.S. National Institutes of Health and U.S. Department of Defense., Competing Interests: Declaration of interests All the other authors declare that they have no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Anemia is a potential adverse effect of phlebotomy during participation in research. Clinical studies of acute HIV infection (AHI) require frequent phlebotomy to maximize scientific yield, but this participant population may also be at increased risk for anemia and other adverse events., Objective: The objective of this study was to describe baseline and longitudinal hemoglobin changes among participants with AHI., Methods: Participants with AHI (n = 202) were enrolled in a prospective cohort study in Thailand. AHI was diagnosed using pooled nucleic acid testing and sequential HIV antibody immunoassays. Antiretroviral therapy was initiated on enrollment. During 48 weeks of study participation, a total of 629 mL of blood was drawn over 14 visits. Hemoglobin levels were measured serially, and abnormalities were graded using the Division of AIDS (National Institute of Allergy and Infectious Diseases) adverse event table., Results: AHI was diagnosed at a median of 18 days after infection. Mean hemoglobin at enrollment of male participants was 14.8 g/dL, and for females, it was 13.0 g/dL. Over 48 weeks, there was a mean increase of 0.2 g/dL among men (P = 0.01) and a decrease of 0.7 g/dL among women (P = 0.03). The overall prevalence of anemia was low, with 7 (3.5%) of 202 fulfilling grade 1 or 2 anemia criteria., Conclusions: Anemia was rare after frequent phlebotomy in research participants with AHI, before and after antiretroviral therapy. Given that the blood volume drawn from this study did not pose substantial clinical risk, increasing the volume of blood drawn for research purposes in acute HIV-infected research participants could be considered for future studies.