Acute HIV Infection Research Articles

Impact of antiretroviral therapy in primary HIV infection on natural killer cell function and the association with viral rebound and HIV DNA following treatment interruption.

Natural Killer (NK) cells play a key role in controlling HIV replication, with potential downstream impact on the size of the HIV reservoir and likelihood of viral rebound after antiretroviral therapy (ART) cessation. It is therefore important to understand how primary HIV infection (PHI) disrupts NK cell function, and how these functions are restored by early ART. We examined the impact of commencing ART during PHI on phenotypic and functional NK cell markers at treatment initiation (baseline), 3 months, 1 year, and 2 years in seven well-characterised participants in comparison to HIV seronegative volunteers. We then examined how those NK cell properties differentially impacted by ART related to time to viral rebound and HIV DNA levels in 44 individuals from the SPARTAC trial who stopped ART after 48 weeks treatment, started during PHI. NK cell markers that were significantly different between the seven people with HIV (PWH) treated for 2 years and HIV uninfected individuals included NKG2C levels in CD56dim NK cells, Tim-3 expression in CD56bright NK cells, IFN-γ expressed by CD56dim NK cells after IL-12/IL-18 stimulation and the fraction of Eomes-/T-bet+ in CD56dim and CD56bright NK cells. When exploring time to viral rebound after stopping ART among the 44 SPARTAC participants, no single NK phenotypic marker correlated with control. Higher levels of IL-12/IL-18 mediated NK cell degranulation at baseline were associated with longer times to viral rebound after treatment interruption (P=0.028). Additionally, we found higher fractions of CD56dim NK cells in individuals with lower levels of HIV DNA (P=0.048). NKG2A and NKp30 levels in CD56neg NK cells were higher in patients with lower HIV DNA levels (p=0.00174, r=-0.49 and p=0.03, r= -0.327, respectively) while CD27 levels were higher in those with higher levels of HIV DNA (p=0.026). These data show NK cell functions are heterogeneously impacted by HIV infection with a mixed picture of resolution on ART, and that while NK cells may affect HIV DNA levels and time to viral rebound, no single NK cell marker defined delayed viral rebound.

Rapid Loss of CD4 T Cells by Pyroptosis during Acute SIV Infection in Rhesus Macaques.

ABSTRACTThe mechanisms underlying depletion of CD4 T cells during acute HIV-1 infection are not well understood. Here we show that caspase-1-induced pyroptosis, a highly inflammatory programmed cell death pathway, is the dominant mechanism responsible for the rapid depletion of CD4 T cells in gut-associated lymphatic tissue (GALT), spleen, and lymph nodes during acute simian immunodeficiency virus (SIV) infection in rhesus macaques. Upregulation of interferon-gamma inducible factor 16, a host DNA sensor that triggers pyroptosis, was also observed in tissue-resident CD4 T cells and correlated with viral loads and CD4 T cell loss. In contrast, caspase-3-mediated apoptosis and viral cytotoxicity only accounted for a small fraction of CD4 T cell death. Other programmed cell death mechanisms, including mitochondria-induced caspase-independent cell death, necroptosis, and autophagy, did not significantly contribute to CD4 T cell depletion. These data support a model in which caspase-1-mediated pyroptosis is the principal mechanism that results in CD4 T cell loss in the GALT and lymphoid organs and release of proinflammatory cytokines. These findings contribute to our understanding of the pathogenesis of acute SIV infection and have important implications for the development of therapeutic strategies.IMPORTANCE Different mechanisms for CD4 T cell depletion during acute HIV-1 infection have been proposed. In this study, we demonstrate that in early simian immunodeficiency virus infection, depletion of CD4 T cells is primarily due to pyroptosis. Other mechanisms may also contribute in a minor way to CD4 T cell depletion.

The first case of monkeypox virus and acute HIV infection: Should we consider monkeypox a new possible sexually transmitted infection?

Since May 2022, a Monkeypox virus (MPXV) outbreak has been ongoing in several non-endemic countries. MPXV is usually transmitted after intimate contact, through body fluids, close contact from active lesions or through respiratory droplets. The recent outbreak occurrent in people with multiple recent sexual intercourse suggests the sexual route as the main way of transmission. However, there is no sufficient evidence to consider MPXV as a new sexually transmitted infection (STI), even though we believe that a link between MPXV and other STIs may exist with a possible facilitating action on their spreading. Herein, we illustrate the first case described during the current outbreak of a young man with both MPXV and acute HIV infection in a non-endemic country.

Understanding the role of traditional healers in the HIV care cascade: Findings from a qualitative study among stakeholders in Mwanza, Tanzania.

Tanzania is HIV-endemic, with 5% prevalence. However, less than half of Tanzanians are aware of their HIV status, and only 75% of adult Tanzanians living with HIV are on antiretroviral therapy (ART). Informal healthcare providers, such as traditional healers, frequently serve as the first line of healthcare in Tanzania. How traditional healers interact with people living with HIV (PLWH) remains unknown. This study sought to understand gaps in HIV care and explore how traditional healers interface with PLWH along the HIV care cascade. We conducted a qualitative study in Mwanza, Tanzania, between November 2019 and May 2020. We invited 15 traditional healers, 15 clients of traditional healers, 15 biomedical healthcare facility staff, and 15 PLWH to participate in a single qualitative interview. Two community focus groups were held with eight male and eight female participants. Participants were 18 years of age or older. Individual experiences with traditional healers and biomedical healthcare facilities, as well as perceptions of traditional healers with respect to HIV care, were explored through interviews. Using a content-analysis approach, codes were grouped into a framework that characterized how traditional healers engage with PLWH throughout the HIV care cascade. PLWH engaged with traditional healers throughout the HIV care cascade, from pre- to post-HIV diagnosis. Traditional healers were described in some cases as facilitating HIV testing, while others were described as delaying testing by providing traditional treatments for HIV symptoms. Traditional medications were frequently used concurrently with ARTs by PLWH. There was concern that healers contributed to ART nonadherence as some PLWH used traditional therapies in search of a "cure" for HIV. Our findings suggest that traditional healers interact with PLWH throughout the HIV care continuum and that collaboration between traditional healers and biomedical healthcare professionals and facilities is needed to improve HIV treatment outcomes.

Burden of sexually transmitted infections from acute HIV infection among women in South Africa: Evidence from a prospective cohort study

PurposeHIV and other sexually transmitted infections (STIs) often co-occur. However, less evidence exists on the long-term STI dynamics among persons living with HIV in sub-Saharan Africa to inform interventions. We investigated the incidence, prevalence and factors associated with STIs, starting from acute HIV infection in a cohort of South African women. MethodsThe CAPRISA002 study enrolled women with acute HIV infection and performed STI testing and treatment 1-2 times annually from 2004-2020. We estimated STI incidence, re-infection, and prevalence trends before and after antiretroviral treatment (ART). We fitted Cox regression models to identify factors associated with STIs. ResultsWe followed up 235 women (median age = 25 years, IQR 22-29) for 7.5 years (IQR 5.7-10.8). New STI and re-infection cases per 100 person-years (PYs) were 5.1 and 9.5 for Neisseria gonorrhoeae (NG), 7.4 and 14.7 for Chlamydia trachomatis (CT), 8.0 and 26.6 for Trichomonas vaginalis (TV), 7.7 and 16.7 for Mycoplasma genitalium (MG) and 25.2 and 37.3 for any STI. STI incidence, was associated with HIV log10 viral load (AHR = 1.24, 95% CI 1.06-1.44), active syphilis (AHR = 16.55, 95% CI 7.49-36.55), a positive HSV-2 PCR (AHR = 1.54, 95% CI 1.01-2.35), bacterial vaginosis (AHR = 1.48, 95% CI 1.01-2.18), recent regular sexual partners at enrolment (one vs none: AHR = 2.62, 95% CI 1.41-4.87; two plus vs none: AHR = 3.68, 95% CI 1.79-7.59) and age (5-year fold: AHR = 0.80, 95% CI 0.70-0.92). ConclusionThe persistent STI/HIV co-infection burden among South African women highlights that early HIV diagnosis and ART initiation needs to be combined with better STI care for women and their partners to prevent HIV and STI transmission.

The potential role of exosomal miRNAs and membrane proteins in acute HIV-infected people.

Exosomes play an important role during human immunodeficiency virus (HIV) acute infection. Yet, information regarding its cargo and its association with HIV rapid progressors (RPs) and typical progressors (TPs) remain largely unknown. In this study, exosomal miRNAs sequencing and mass cytometry were used to identify differential exosomal miRNAs and membrane proteins that participate in the pathogenesis of TPs and RPs. We discovered that miR-144-5p, miR-1180-3p, miR-451a, miR-362-5p, and miR-625-5p are associated with the TPs and miR-362-5p with the RPs. Decreased autophagy, amino acid metabolism, immune response, and IL-6 are closely related to RPs. In addition, SP1 was selected as the most significant transcription factor (TF) associated with disease progression. CD49D, CD5, CCR5, CD40, CD14, and CD86 were selected as the differential exosomal membrane proteins between TPs and RPs. This study provides valuable information for clarifying the mechanism in people with acute HIV infection.

FoxP3+ CD8 T-cells in acute HIV infection and following early antiretroviral therapy initiation.

ObjectivesBesides CD4 regulatory T-cells (Tregs), immunosuppressor FoxP3+ CD8 T-cells are emerging as an important subset of Tregs, which contribute to immune dysfunction and disease progression in HIV infection. However, FoxP3+ CD8 T-cell dynamics in acute HIV infection and following early antiretroviral therapy (ART) initiation remain understudied.MethodsSubsets of FoxP3+ CD8 T-cells were characterized both prospectively and cross-sectionally in PBMCs from untreated acute (n=26) and chronic (n=10) HIV-infected individuals, early ART-treated in acute infection (n=10, median of ART initiation: 5.5 months post-infection), ART-treated in chronic infection (n=10), elite controllers (n=18), and HIV-uninfected controls (n=21).ResultsAcute and chronic infection were associated with increased total, effector memory, and terminally differentiated FoxP3+ CD8 T-cells, while early ART normalized only the frequencies of total FoxP3+ CD8 T-cells. We observed an increase in FoxP3+ CD8 T-cell immune activation (HLADR+/CD38+), senescence (CD57+/CD28-), and PD-1 expression during acute and chronic infection, which were not normalized by early ART. FoxP3+ CD8 T-cells in untreated participants expressed higher levels of immunosuppressive LAP(TGF-β1) and CD39 than uninfected controls, whereas early ART did not affect their expression. The expression of gut-homing markers CCR9 and Integrin-β7 by total FoxP3+ CD8 T-cells and CD39+ and LAP(TGF-β1)+ FoxP3+ CD8 T-cells increased in untreated individuals and remained higher than in uninfected controls despite early ART. Elite controllers share most of the FoxP3+ CD8 T-cell characteristics in uninfected individuals.ConclusionsAlthough early ART normalized total FoxP3+ CD8 T-cells frequencies, it did not affect the persistent elevation of the gut-homing potential of CD39+ and LAP(TGF-β1)+ FoxP3+ CD8 T-cell, which may contribute to immune dysfunction.

Sexual Behavior Transition and Acute and Early HIV Infection Among Men Who Have Sex With Men: Evidence from an Open Cohort in China, 2011-2019.

The present study examined how sexual behaviors transit over time among men who have sex with men (MSM) and whether these transitions were associated with acute and early HIV (AEH) infection. An open cohort study was conducted using snowball sampling to recruit MSM via physical venues and Internet venues from 2011 to 2019, in China. Cox models were used to estimate the correlates of risk factors and AEH infection. We used Latent Transition Analysis (LTA) to describe behavioral profile and explore latent behavioral "trans-phenotypes," then examined the effect between different "trans-phenotypes" and AEH infection risk and explored the effect of characteristics as possible predictors of sexual behavior transition. Of 6502 MSM, a total of 1974 individuals with negative human immunodeficiency virus (HIV) tests at baseline and at least 2 visit records were included in the final analysis from 2011 to 2019. During an average 1.84years of follow-up, 64 AEH infections were documented. In the multivariable Cox model, the association between condom use in last anal sex (HR: 0.095, 0.038-0.205), fewer sexual partners (HR: 0.375, 0.205-0.712), low frequency of condom use (HR: 3.592, 1.186-11.272), and AEH acquisition were found. The percentage of MSM with "maintain/develop safety-profile," "consistent risky-profile," and "safety-profile to risky-profile" were 52.48, 40.17, and 7.35%, respectively. Compared with "maintain\develop safety-profile," "consistent or develop risky-profile" had an increasing likelihood of AEH infection. Meanwhile, male sex workers (MSWs) or older MSM were more likely to consist or transit in "risky-profile." Having middle education is a risk factor to transit in "risky-profile" for MSM with "safety-profile" at baseline. In addition, MSM who accept health services in the past year engaged in higher proportion of developing safety-profile. Approximately half of MSM maintain or develop risky behavior with the increasing likelihood of AEH acquisition in China, which suggested that targeted and intensive interventions should be prioritized to maintain safety-profile. Clinical Trial Number: ChiCTR2000039500.

Effective Treatment of Patients Experiencing Primary, Acute HIV Infection Decreases Exhausted/Activated CD4+ T Cells and CD8+ T Memory Stem Cells.

Several studies have identified main changes in T- and B-lymphocyte subsets during chronic HIV infection, but few data exist on how these subsets behave during the initial phase of HIV infection. We enrolled 22 HIV-infected patients during the acute stage of infection before the initiation of antiretroviral therapy (ART). Patients had blood samples drawn previous to ART initiation (T0), and at 2 (T1) and 12 (T2) months after ART initiation. We quantified cellular HIV-DNA content in sorted naïve and effector memory CD4 T cells and identified the main subsets of T- and B-lymphocytes using an 18-parameter flow cytometry panel. We identified correlations between the patients’ clinical and immunological data using PCA. Effective HIV treatment reduces integrated HIV DNA in effector memory T cells after 12 months (T2) of ART. The main changes in CD4+ T cells occurred at T2, with a reduction of activated memory, cytolytic and activated/exhausted stem cell memory T (TSCM) cells. Changes were present among CD8+ T cells since T1, with a reduction of several activated subsets, including activated/exhausted TSCM. At T2 a reduction of plasmablasts and exhausted B cells was also observed. A negative correlation was found between the total CD4+ T-cell count and IgM-negative plasmablasts. In patients initiating ART immediately following acute/early HIV infection, the fine analysis of T- and B-cell subsets has allowed us to identify and follow main modifications due to effective treatment, and to identify significant changes in CD4+ and CD8+ T memory stem cells.

Pregnancy rates and outcomes in a longitudinal HIV cohort in the context of evolving antiretroviral treatment provision in South Africa

BackgroundIn South Africa, women continue to face a high burden of Human Immunodeficiency Virus (HIV) infection and the possible complications thereof during pregnancy. We assessed pregnancy incidence rates and outcomes in a longitudinal HIV cohort study over a 15-year period.MethodsWe evaluated pregnancies among women ≥ 18 years between 2004 and 2019 in the CAPRISA 002 study. We analysed pregnancy rates following HIV acquisition, CD4 counts and HIV viral load dynamics and pregnancy outcomes. We used linear regression to assess if the mean CD4 and log10 viral load close to delivery increases or decreases linearly across three different timepoints.ResultsIn total 245 women enrolled into the HIV negative study phase, 225 into the HIV infection phase and 232 in the antiretroviral therapy (ART) phase. Median follow-up time was 2.0 years [Interquartile Range (IQR) 0.8–2.0] during the HIV negative phase, 2.6 years; (IQR) 1.2–4.8] during HIV infection and 3.7 years (IQR 1.8–5.0) on ART, with maximum follow-up time of 2, 10 and 6 years respectively. Overall, 169 pregnancies occurred in 140 women, of which 16 pregnancies were observed during acute or early HIV infection [Incidence Rate (IR) 8.0 per 100 women-years; 95% confidence interval (CI): 4.6—12.9], 48 during established infection [IR 9.3; (CI 6.8–12.3)] and 68 on ART [IR 8.9; (CI: 7.0 – 11.4)]. Birth outcomes from 155/169 (91.7%) pregnancies were 118 (76.1%) full term live births, 17 (10.9%) premature live births, 9 (5.8%) therapeutic/elective miscarriages, 8 (5.1%) spontaneous miscarriages and 3 (1.9%) spontaneous foetal deaths or stillbirths. Six mother-to-child transmission events occurred, with four documented prior to 2008. Over time, mean CD4 count in pregnant women increased from 395 cells/µL (2004—2009) to 543 cells/µL (2010–2014) and to 696 cells/µL (2015–2019), p < 0.001. Conversely, the viral load declined from 4.2 log10 copies/ml to 2.5 log10 copies/ml and to 1.2 log10 copies/ml (p < 0.001) for the corresponding periods.ConclusionsPregnancy rates following HIV acquisition were high, emphasising a need for timeous ART provision and contraception counselling in women recently diagnosed with HIV. CD4 count and HIV viral load trajectories reflect improvements in treatment guidance for pregnant women over time.

Neuropathogenesis of HIV-1: insights from across the spectrum of acute through long-term treated infection.

This review outlines the neuropathogenesis of HIV, from initial HIV entry into the central nervous system (CNS) to chronic infection, focusing on key advancements in the last 5years. Discoveries regarding acute HIV infection reveal timing and mechanisms of early HIV entry and replication in the CNS, early inflammatory responses, and establishment of genetically distinct viral reservoirs in the brain. Recent studies additionally explore how chronic HIV infection is maintained in the CNS, examining how the virus remains in a latent "hidden" state in diverse cells in the brain, and how this leads to sustained pathological inflammatory responses. Despite viral suppression with antiretroviral therapy, HIV can persist and even replicate in the CNS, and associate with ongoing neuropathology including CD8 + T-lymphocyte mediated encephalitis. Crucial investigation to advance our understanding of the immune mechanisms that both control viral infection and lead to pathological consequences in the brain is necessary to develop treatments to optimize long-term neurologic health in people living with HIV.

Acute HIV-1 infection viremia associate with rebound upon treatment interruption

Analytic treatment interruption (ATI) studies evaluate strategies to potentially induce remission in people living with HIV-1 but are often limited in sample size. We combined data from four studies that tested three interventions (vorinostat/hydroxychloroquine/maraviroc before ATI, Ad26/MVA vaccination before ATI, and VRC01 antibody infusion during ATI). The statistical validity of combining data from these participants was evaluated. Eleven variables, including HIV-1 viral load at diagnosis, Fiebig stage, and CD4+ Tcell count were evaluated using pairwise correlations, statistical tests, and Cox survival models. Participants had homogeneous demographic and clinical characteristics. Because an antiviral effect was seen in participants who received VRC01 infusion post-ATI, these participants were excluded from the analysis, permitting a pooled analysis of 53 participants. Time to viral rebound was significantly associated with variables measured at the beginning of infection: pre-antiretroviral therapy (ART) viral load (HR= 1.34, p= 0.022), time to viral suppression post-ART initiation (HR= 1.07, p<0.001), and area under the viral load curve (HR= 1.34, p= 0.026). We show that higher viral loads in acute HIV-1 infection were associated with faster viral rebound, demonstrating that the initial stage of HIV-1 infection before ART initiation has a strong impact on viral rebound post-ATI years later. This work was supported by a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the US Department of the Army (W81XWH-18-2-0040). This research was funded, in part, by the US National Institute of Allergy and Infectious Diseases (AAI20052001) and the I4C Martin Delaney Collaboratory (5UM1AI126603-05).

Individual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection.

ABSTRACTObjectiveWe examined individual differences in CD4/CD8 T-cell ratio trajectories and associated risk profiles from acute HIV infection (AHI) through 144 weeks of antiretroviral therapy (ART) using a data-driven approach.MethodsA total of 483 AHI participants began ART during Fiebig I–V and completed follow-up evaluations for 144 weeks. CD4+, CD8+, and CD4/CD8 T-cell ratio trajectories were defined followed by analyses to identify associated risk variables.ResultsParticipants had a median viral load (VL) of 5.88 copies/ml and CD4/CD8 T-cell ratio of 0.71 at enrollment. After 144 weeks of ART, the median CD4/CD8 T-cell ratio was 1.3. Longitudinal models revealed five CD4/CD8 T-cell ratio subgroups: group 1 (3%) exhibited a ratio >1.0 at all visits; groups 2 (18%) and 3 (29%) exhibited inversion at enrollment, with normalization 4 and 12 weeks after ART, respectively; and groups 4 (31%) and 5 (18%) experienced CD4/CD8 T-cell ratio inversion due to slow CD4+ T-cell recovery (group 4) or high CD8+ T-cell count (group 5). Persistent inversion corresponded to ART onset after Fiebig II, higher VL, soluble CD27 and TIM-3, and lower eosinophil count. Individuals with slow CD4+ T-cell recovery exhibited higher VL, lower white blood cell count, lower basophil percent, and treatment with standard ART, as well as worse mental health and cognition, compared with individuals with high CD8+ T-cell count.ConclusionsEarly HIV disease dynamics predict unfavorable CD4/CD8 T-cell ratio outcomes after ART. CD4+ and CD8+ T-cell trajectories contribute to inversion risk and correspond to specific viral, immune, and psychological profiles during AHI. Adjunctive strategies to achieve immune normalization merit consideration.

How could HIV-1 drug resistance impact preexposure prophylaxis for HIV prevention?

To review current laboratory and clinical data on the frequency and relative risk of drug resistance and range of mutations selected from approved and investigational antiretroviral agents used for preexposure prophylaxis (PrEP) of HIV-1 infection, including tenofovir disproxil fumarate (TDF)-based oral PrEP, dapivirine ring, injectable cabotegravir (CAB), islatravir, lenacapavir and broadly neutralizing antibodies (bNAbs). The greatest risk of HIV-1 resistance from PrEP with oral TDF/emtricitabine (FTC) or injectable CAB is from starting or continuing PrEP after undiagnosed acute HIV infection. By contrast, the dapivirine intravaginal ring does not appear to select nonnucleoside reverse transcriptase inhibitor resistance in clinical trial settings. Investigational inhibitors including islatravir, lenacapavir, and bNAbs are promising for use as PrEP due to their potential for sustained delivery and low risk of cross-resistance to currently used antiretrovirals, but surveillance for emergence of resistance mutations in more HIV-1 gene regions (gag, env) will be important as the same drugs are being developed for HIV therapy. PrEP is highly effective in preventing HIV infection. Although HIV drug resistance from PrEP use could impact future options in individuals who seroconvert on PrEP, the current risk is low and continued monitoring for the emergence of resistance and cross-resistance during product development, clinical studies, and product roll-out is advised to preserve antiretroviral efficacy for both treatment and prevention.

Pediatric AIDS-Therapeutic Successes Built on a Foundation of Pediatric Clinical Pharmacology with Pharmacokinetic-Pharmacodynamic Modeling.

Pediatric AIDS-Therapeutic Successes Built on a Foundation of Pediatric Clinical Pharmacology with Pharmacokinetic-Pharmacodynamic Modeling.

The Impact of Early Antiretroviral Treatment (ART) for HIV on the Sensitivity of the Latest Generation of Blood Screening and Point of Care Assays.

Introduction: Rapid initiation of antiretroviral therapy (ART) in early HIV infection is important to limit seeding of the viral reservoir. A number of studies have shown that if ART is commenced prior to seroconversion, the seroconversion may, or may not, occur. We aimed to assess whether seroreversion or no seroconversion occurs using samples collected during an early treatment study in South Africa. Methods: We tested 10 longitudinal samples collected over three years from 70 blood donors who initiated ART after detection of acute or early HIV infection during donation screening on fourth- and fifth-generation HIV antibody and RNA assays, and three point of care (POC) rapid tests. Donors were allocated to three treatment groups: (1) very early, (2) early, and (3) later. Longitudinal samples were grouped into time bins post-treatment initiation. Results: On all three high-throughput HIV antibody assays, no clear pattern of declining signal intensity was observed over time after ART initiation in any of the treatment initiation groups and 100% detection was obtained. The Abbott Determine POC assay showed 100% detection at all time points with no seroreversion. However, the Abbott ABON HIV1 and OraSure OraQuick POC assays showed lower proportions of detection in all time bins in the very early treated group, ranging from 50.0% (95% CI: 26.8–73.2%) to 83.1% (95% CI: 64.2–93.0%), and moderate detection rates in the early and later-treated groups. Conclusion: While our findings are generally reassuring for HIV detection when high-throughput serological screening assays are used, POC assays may have lower sensitivity for detection of HIV infection after early treatment. Findings are relevant for blood safety and other settings where POC assays are used.

Characteristics of recent HIV infection among individuals newly diagnosed as HIV-positive in South Korea (2008–2015)

Most HIV-positive individuals diagnosed in Korea are infected through sexual contact, with the time of HIV infection therefore often being unknown. The aim of this study was to investigate the characteristics of diagnosed patients near the time of HIV seroconversion to establish useful HIV intervention strategies. Cross-sectional study. Newly diagnosed HIV cases based on the national HIV surveillance system in South Korea, 2008–2015. To distinguish recent from long-standing HIV infection among 5898 nationwide HIV-positive specimens, limiting antigen avidity assays (Sedia HIV-1 LAg-Avidity EIA, cut-off = 1.5) were performed. Data on CD4+ T cell count at HIV diagnosis and death from AIDS within one year after first HIV diagnosis were used to distinguish recent HIV infections. Acute HIV infection is characterized by detectable HIV RNA or HIV p24 antigen levels, along with a negative or indeterminate antibody western blot result, but with the subject subsequently testing positive after a predetermined period. We analyzed the characteristics of recent and acute HIV infections by sex, age, nationality, HIV testing site, region, and reason for HIV testing. Recent and acute HIV infections were described as the proportion of recent and acute HIV infections among newly-diagnosed cases in a given year. Recent and acute HIV infections over the 8-year study period were 20.5% (1210/5898) and 9.5% (562/5898), respectively. Both infections were generally higher in the following groups: males, younger age, Koreans, individuals who were tested due to disease, residents of smaller city or rural area, and individuals diagnosed in recent calendar years. Acute infections were significantly higher among individuals tested in hospitals and due to suspected HIV infection. The recent and acute HIV infection in younger age groups (< 30 years) has been increasing in a given year. There was an increase in the proportion of young individuals with recent HIV infection, and we identified risk groups more at risk of HIV infection recently in Korea. Therefore, our results could prove useful for the development and assessment of national HIV prevention strategies in Korea and provide valuable data for further HIV research.

Dolutegravir in real life: Self-reported mental and physical health outcomes after transitioning from efavirenz- to dolutegravir-based antiretroviral therapy in a prospective cohort study in Lesotho.

HIV programmes across many countries in Africa have recently transitioned people living with HIV from efavirenz (EFV)- to dolutegravir (DTG)-containing antiretroviral therapy (ART). As both drugs are associated with neuropsychiatric adverse effects, this study assessed the mental health and HIV/ART-associated symptoms of people living with HIV before and after transition to DTG. The prospective DO-REAL cohort enrolled people starting DTG-based ART in Lesotho from February to December 2020. For this analysis within DO-REAL, we included adults changing from tenofovir disoproxil fumarate (TDF)/lamivudine (3TC)/EFV to TDF/3TC/DTG within first-line therapy. At transition and 16 weeks thereafter, participants completed the Patient Health Questionnaire-9 (PHQ-9; depression screening), the 12-item Short-Form Health Survey (SF-12; mental and physical health), and a modified HIV Symptom Index (mHSI; HIV/ART-related symptoms). We also assessed weight change. We used McNemar tests with Bonferroni corrections to assess binary outcomes. gov: NCT04238767. Among 1228 participants, 1131 completed follow-up. Of these, 60.0% were female, the median age was 46 years (interquartile range [IQR] 38-55), and the median time taking ART was 5.7 years (IQR 3.5-8.9). No change was observed for weight or overall PHQ-9 or SF-12 outcomes. However, three mHSI items decreased at follow-up: 'feeling sad/down/depressed' (bothered 6.0% vs. 3.3% of participants at least 'a little' before vs. after transition; adjusted p=0.048); 'feeling nervous/anxious' (7.4% vs. 3.4%; adjusted p=0.0009); and 'nightmares, strange/vivid dreams' (6.3% vs. 3.5%; adjusted p=0.027). Individual PHQ-9 or SF-12 items also improved. Being symptom free across all measures increased from 5.1% to 11.4% (p < 0.0001). We observed no negative impacts and potential moderate improvements with DTG, providing further support for the rollout of DTG.

Care engagement with healthcare providers and symptom management self-efficacy in women living with HIV in China: secondary analysis of an intervention study

BackgroundSymptom management self-efficacy is a prerequisite for individuals to fully manage their symptoms. The literature reports associations between engagement with healthcare providers (HCPs), internalized stigma, and types of self-efficacy other than symptom management. However, the factors of symptom management self-efficacy are not well understood. This study aimed to investigate the relationship among engagement with HCPs, internalized stigma, and HIV symptom management self-efficacy in Chinese women living with HIV (WLWH).MethodsThis current analysis was part of the original randomized control trial, we used data collected from 41 women living with HIV (WLWH) assigned to an intervention arm or a control arm from Shanghai and Beijing, China, at baseline, Week 4 and Week 12. The CONSORT checklist was used. The study was registered in the Clinical Trial Registry (#NCT03049332) on 10/02/2017.ResultsThe results demonstrate that HCPs should increase engagement with WLWH when providing care, thereby improving their symptom management self-efficacy. The results suggested that participants’ engagement with HCPs was significantly positively correlated with their HIV symptom management self-efficacy in the latter two time points. Internalized stigma was significantly negatively correlated with HIV symptom management self-efficacy only at the 4-week follow-up.ConclusionsThis study demonstrated the positive effect of engagement with HCPs on WLWHs’ symptom management self-efficacy as well as the negative effect of internalized stigma on symptom management self-efficacy. Future research can further test the relationship between the three key concepts, as well as explore interventions to decrease internalized stigma.

Immunological, Cognitive, and Psychiatric Outcomes After Initiating Efavirenz- and Dolutegravir-based Antiretroviral Therapy During Acute Human Immunodeficiency Virus Infection.

Efavirenz (EFV)- and dolutegravir (DTG)-based antiretroviral therapy (ART) is the former and current recommended regimen for treatment-naive individuals with human immunodeficiency virus type 1 (HIV-1). Whether they impact the immunological and neuropsychiatric profile differentially remains unclear. This retrospective analysis included 258 participants enrolled during acute HIV-1 infection (AHI). Participants initiated 1 of 3 ART regimens during AHI: EFV-based (n = 131), DTG-based (n = 92), or DTG intensified with maraviroc (DTG/MVC, n = 35). All regimens included 2 nucleoside reverse-transcriptase inhibitors and were maintained for 96 weeks. CD4+ and CD8+ T-cell counts, mood symptoms, and composite score on a 4-test neuropsychological battery (NPZ-4) were compared. At baseline, the median age was 26 years, 99% were male, and 36% were enrolled during Fiebig stage I-II. Plasma viral suppression at weeks 24 and 96 was similar between the groups. Compared with the EFV group, the DTG group showed greater increments of CD4+ (P < .001) and CD8+ (P = .015) T-cell counts but a similar increment of CD4/CD8 ratio at week 96. NPZ-4 improvement was similar between the 2 groups at week 24 but greater in the DTG group at week 96 (P = .005). Depressive mood and distress symptoms based on the Patient Health Questionnaire and distress thermometer were similar between the 2 groups at follow-up. Findings for the DTG/MVC group were comparable to those for the DTG group vs the EFV group. Among individuals with AHI, 96 weeks of DTG-based ART was associated with greater increments of CD4+ and CD8+ T-cell counts and improvement in cognitive performance.