Early Antiretroviral Treatment Initiation Research Articles

Differences in neuroinflammation in people who started antiretroviral treatment during primary versus chronic HIV infection: an 18kDa Translocator protein (TSPO) positron emission tomography (PET) study.

Persistent inflammation is described in people with HIV (PWH) on antiretroviral treatment (ART). Early ART initiation is associated with reduced inflammation. We aimed to evaluate neuroinflammation, using translocator protein (TSPO) [11C]PBR28 PET neuroimaging in PWH who initiated ART during acute HIV (aPWH) versus chronic HIV infection (cPWH) versus a control population. This was a cross-sectional, observational study. All participants underwent [11C]PBR28 PET-CT neuroimaging. Using a two-tissue compartment model, total volume of distribution (VT) and distribution volume ratios (DVR) using cortical grey matter as a pseudo-reference region at 20 regions of interest (ROIs) were calculated. Differences in VT and DVR were compared between groups using the Kruskall-Wallis test. Seventeen neuro-asymptomatic male PWH on ART (9 aPWH, 8 cPWH) and 8 male control participants (CPs) were included. Median (interquartile range, IQR) age was 40 (30, 46), 44 (41, 47) and 21 (20, 25) years in aPWH, cPWH and CPs, respectively. Median (IQR) CD4 (cells/µL) and CD4:CD8 were 687 (652, 1014) and 1.37 (1.24, 1.42), and 700 (500, 720) and 0.67 (0.64, 0.82) in aPWH and cPWH, respectively. Overall, no significant difference in VT and DVR were observed between the three groups at any ROIs. cPWH demonstrated a trend towards higher mean VT compared with aPWH and CPs at most ROIs. No significant differences in neuroinflammation, using [11C]PBR28 binding as a proxy, were identified between cPWH, aPWH and CPs. A trend towards lower absolute [11C]PBR28 binding was seen amongst aPWH and CPs, suggesting early ART may mitigate neuroinflammation.

Factors associated with late initiation of antiretroviral therapy in Iran’s HIV/AIDS surveillance data

Early initiation of Antiretroviral Treatment (ART) in HIV patients is essential for effectively suppressing the viral load and prognosis. This study utilized National HIV/AIDS Surveillance Data in Iran to identify factors associated factors with the duration to initiate ART. This hybrid cross-sectional historical cohort study was conducted on Iran’s National HIV/AIDS Surveillance Data from 2001 to 2019. Sociodemographic characteristics, route of transmission, HIV diagnosis date, and ART initiation date were collected. Multivariable linear and quantile regression models were employed to analyze the duration to initiate ART by considering predictor variables. This study included 17,062 patients (mean age 34.14 ± 10.77 years, 69.49% males). Multivariate quantile regression coefficients varied across different distributions of the dependent variable (i.e., duration to initiate ART) for several independent variables. Generally, male gender, injecting drug use (IDU), and having an HIV-positive spouse were significantly associated with an increased duration to initiate ART (p < 0.05). However, a significant decrease was observed in older patients, those with a university level education, men who had sex with men (MSM), and patients diagnosed after 2016 (p < 0.05). Despite improvements in the duration to initiate ART after implementing the WHO’s 2016 program in Iran, various sociodemographic groups were still vulnerable to delayed ART initiation in the region. Therefore, programs including early testing, early ART initiation, active care, educational and cultural interventions, and appropriate incentives are required for these groups.

Analysis of Morbidity and Mortality Factors among HIV-Infected Children in the Communal Medical Centres of the Municipality of Ratoma

Introduction: The objective of this study was to analyse the morbidity and mortality factors of HIV-infected children. Material and Methods: This was a 10-year retrospective study from 1 January 2012 to 31 December 2021. All children aged 0-15 years with a positive HIV serological test or PCR under antiretroviral treatment and having a medical file were followed up in the two CMCs of the Ratoma commune. Results: We collected 183 records of HIV-infected children on antiretroviral treatment. The median age was 3 years with extremes of 2 months and 15 years. More than half (60.1%) were &lt;5 years old. More than half of the children (65.1%) were at WHO clinical stage (3 and 4). 60.8% had anemia with a median hemoglobin level of 10.7 g/dl. Respiratory diseases (39.34%) were the most common morbid events. Almost half (44.3%) were alive and followed up, 17.5% died, 23.5% lost to follow-up and 14.8% transferred. Anemia (18.75%) was the most common cause of death. Maternal non-education (p = 0.001), very low income (p = 0.0001), clinical screening (p = 0.0003), severe immunodepression (p = 0.002), tuberculosis (p = 0.007), clinical stage 3 (p = 0.0001) were the main risk factors associated with deaths. Conclusion: The application of the new WHO recommendations for medical management, which require early initiation of antiretroviral treatment, the improvement of PMTCT performance and the promotion of systematic screening are necessary to reduce the morbidity and mortality of HIV-infected children in our context.

Incidence, recurrence, and prevalence of bacterial vaginosis from acute to chronic HIV infection in a prospective cohort of women in South Africa

We investigated the incidence, recurrence, prevalence, and risk factors for bacterial vaginosis (BV) diagnosis starting from acute HIV infection among South African women. The Centre for the AIDS Programme of Research in South Africa 002 study tested and treated women for BV (Nugent score 7-10) once/twice annually from acute to chronic HIV infection (2004-2020). We estimated BV incidence as the number of new cases and recurrence as the number of subsequent diagnoses per 100 person-years (PYs). We fitted Anderson-Gil Cox-proportional-hazard regression models to determine factors associated with BV incidence or recurrence. Of 235 participants, the median age at enrollment was 25 years (Inter Quartile Range [IQR] 22-29). BV prevalence at enrollment was 50.6%. BV incidence was 23.9 cases per 100 PYs, and recurrence was 51.3 cases per 100 PYs. BV incidence/recurrence was associated with younger age (<25 years: adjusted hazard ratio [aHR] 1.70, 95% confidence interval [CI] 1.27-2.27), detectable HIV viral load (aHR 1.54, 95% CI 1.27-1.87) and lower CD4 count (<350 cells/μL: aHR 1.33, 95% CI 1.01-1.76). Our findings underscore the need for early antiretroviral treatment initiation with diagnostic BV and sexually transmitted infection care, especially among younger women.

HIV-1 reservoir evolution in infants infected with clade C from Mozambique

BackgroundThe persistence of HIV-1-infected cells during antiretroviral therapy is well documented but may be modulated by early initiation of antiretroviral therapy in infants. MethodsHere, we longitudinally analyzed the proviral landscape in nine infants with vertical HIV-1 infection from Mozambique over a median period of 24 months, using single-genome, near full-length, next-generation proviral sequencing. ResultsWe observed a rapid decline in the frequency of intact proviruses, leading to a disproportional under-representation of intact HIV-1 sequences within the total number of HIV-1 DNA sequences after 12-24 months of therapy. In addition, proviral integration site profiling in one infant demonstrated clonal expansion of infected cells harboring intact proviruses and indicated that viral rebound was associated with an integration site profile dominated by intact proviruses integrated into genic and accessible chromatin locations. ConclusionTogether, these results permit rare insight into the evolution of the HIV-1 reservoir in infants infected with HIV-1 and suggest that the rapid decline of intact proviruses, relative to defective proviruses, may be attributed to a higher vulnerability of genome-intact proviruses to antiviral immunity. Technologies to analyze combinations of intact proviral sequences and corresponding integration sites permit a high-resolution analysis of HIV-1 reservoir cells after early antiretroviral treatment initiation in infants.

Health Impact and Cost-Effectiveness of HIV Testing, Linkage, and Early Antiretroviral Treatment in the Botswana Combination Prevention Project.

Background:The Botswana Combination Prevention Project tested the impact of combination prevention (CP) on HIV incidence in a community-randomized trial. Each trial arm had ~55,000 people, 26% HIV prevalence, and 72% baseline ART coverage. Results showed intensive testing and linkage campaigns, expanded antiretroviral treatment (ART), and voluntary male medical circumcision (VMMC) referrals increased coverage and decreased incidence over ~29 months follow-up. We projected lifetime clinical impact and cost-effectiveness of CP in this population.Setting:Rural and peri-urban communities in Botswana.Methods:We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) model to estimate lifetime health impact and cost of 1) earlier ART initiation, and 2) averting an HIV infection, which we applied to incremental ART initiations and averted infections calculated from trial data. We determined the incremental cost-effectiveness ratio (ICER, US$/QALY) for CP vs. standard of care.Results:In CP, 1,418 additional people with HIV initiated ART and an additional 304 infections were averted. For each additional person started on ART, life expectancy increased 0.90 QALYs and care costs increased by $869. For each infection averted, life expectancy increased 2.43 QALYs with $9,200 in care costs saved. With CP, an additional $1.7 million were spent on prevention and $1.2 million on earlier treatment. These costs were mostly offset by decreased care costs from averted infections, resulting in an ICER of $79 per QALY.Conclusions:Enhanced HIV testing, linkage, and early ART initiation improves life expectancy, reduces transmission, and can be cost-effective or cost-saving in settings like Botswana.

Loss to follow-up among human immunodeficiency virus-positive postpartum women and its predictive factors: A retrospective study.

Antiretroviral treatment (ART) is essential in preventing mother-to-child transmission of human immunodeficiency virus (HIV), and postpartum discontinuation of ART is associated with adverse outcomes. This study identified factors associated with postpartum follow-up of HIV-positive women. This was a retrospective cohort study of 170 HIV-infected pregnant women who received regular obstetric examination and delivered successfully in Beijing between 2003 and 2020.The women's sociodemographic, clinical, treatment, obstetric, and gestational characteristics were analyzed. Cox proportional hazards models were used to estimate adjusted hazard ratios (AHRs) of loss to follow-up between levels of confounders. In the multivariable Cox proportional hazard models, women with a longer time from HIV diagnosis to delivery per year had a 1.4-timeshigher risk (AHR=1.433, 95% CI: 0.897-2.229) and a higher rate of loss to follow-up than the other women. Perinatal health care (AHR=0.003,95% CI: 0.000-0.105) and gestational age above 37weeks at delivery (AHR=0.294, 95% CI: 0.005-15.818) were associated with a longer follow-up of postpartum HIV-positive women, when compared to women who did not receive perinatal healthcare and who delivered before 37weeks of gestation, respectively. The longer time from HIV diagnosis to delivery, access to perinatal care, and full-term gestation at delivery improved postpartum ART adherence and follow-up among HIV-positive women. Early initiation of ART, integration of adult ART into prevention of mother-to-child transmission, combination ART with maternal healthcare, and enhanced pregnancy care will improve ART adherence among HIV-positive women after delivery.

Quantification of CD4 Recovery in Early-Treated Infants Living With HIV.

Perinatally HIV-acquired infants benefit from an early antiretroviral treatment initiation. Thanks to a short viral exposure time, their immune system can be maintained or reconstituted, allowing a "normal" immune development. In this study, we mathematically modeled and quantified individual CD4+ T-cell reconstitution of a subset of 276 children who started treatment within 6 months of age and achieved sustained viral suppression. Considering natural age differences in CD4+ T-cell dynamics, we fitted distances to age-matched healthy reference values with a linear model approaching an asymptote. Depleted CD4+ percentages (CD4%) and CD4+ counts (CD4ct) restored healthy levels during treatment. CD4ct recovered with a median rate of 4 cells/µL/d, and individual recovery rates were correlated negatively with their initial CD4ct. CD4 values at onset of treatment decrease with age, whereas recovery times and levels seem to be age-independent. CD4 recovery correlates positively with viral suppression, and the stabilization of CD4 levels usually occurs after viral suppression. CD4 levels stabilize within 3-13 months after treatment initiation. The recovery dynamics of the CD4% is comparable with those of the CD4ct. In early-treated children with successful viral suppression, the CD4 depletion is typically mild and CD4+ T cells tend to "fully" recover in numbers.

Epidemiology of Kaposi's Sarcoma.

Simple SummaryKaposi’s sarcoma is a rare tumor caused by human herpesvirus 8 in the context of immunodeficiency, such as that induced by HIV infection or immunosuppressive therapy. In patients living with HIV (PLHIV), thanks to potent antiretroviral treatment that efficiently restores immunity and allows a better control of HIV infection, the occurrence of KS has decreased dramatically over the past 25 years. However, KS is still one the most frequent cancers in PLHIV, in particular in men who have sex with men and in sub-Saharan Africa, where it is still endemic. Even in the context of restored immunity, the risk of KS is still more than 30 times higher in PLHIV than in the general population.Kaposi’s sarcoma is an angioproliferative tumor caused by human herpesvirus 8 in the context of immunodeficiency, such as that induced by HIV infection or immunosuppressive therapy. Its incidence has dramatically fallen in patients living with HIV (PLHIV) since the introduction of potent antiretroviral combinations 25 years ago due to the restoration of immunity and better control of HIV replication. However, KS is still one of the most frequently occurring cancers in PLHIV, in particular in men who have sex with men and in sub-Saharan Africa, where it is still endemic. Even in the context of restored immunity, the risk of KS is still more than 30 times higher in PLHIV than in the general population. Recent evidence indicates that early initiation of antiretroviral treatment, which is recommended by current guidelines, may reduce the risk of KS but it needs to be accompanied by early access to care. This review mainly focuses on the recent epidemiological features of KS in the context of HIV infection.

Evaluating maternal characteristics and DNA polymerase chain reaction birth testing of neonates born with HIV in a KwaZulu-Natal referral hospital – missed opportunities?

Background. Congenital HIV infection has declined in South Africa with an expanded programme to decrease perinatal HIV transmission. Understanding the challenges within this programme can identify opportunities for improvements. There is an opportunity with birth HIV DNA polymerase chain reaction testing to expedite very early treatment of neonates born with HIV in referral hospitals. Objectives. This study was aimed at describing the characteristics of mothers of neonates born with HIV as well as the evaluation of the access and availability of birth HIV DNA PCR results within a referral hospital. Method. This study was a retrospective chart review of all documented neonates born with HIV delivered between 1 January 2017 and 30 June 2019 at King Edward VIII Hospital, Durban, KwaZulu-Natal. The birth HIV DNA PCR results provided through institutional programmes were analysed, and the clinical characteristics of mothers of neonates born with HIV were described. Results. Review of hospital-based records, during the 30-month study period, identified 6 902 (40.02% of 17 243 total live births) birth HIV DNA PCR tests having been done. During the sample period, documented positive, rejected or indeterminate results were analysed. These results indicated only 37 (0.54%) of known HIV-exposed neonates who were tested, to have a documented positive birth HIV DNA PCR result. Fifty-nine neonates had either indeterminate or rejected results. Negative HIV DNA PCR results could not be verified. Analysis of the mothers of neonates with documented HIV-positive results indicated high mean viral loads of these mothers (52 343 copies/mL) and most were diagnosed in the current pregnancy or at delivery. Conclusion. Review of the characteristics of mothers of neonates born with HIV within a public referral hospital reiterates that late HIV diagnosis is common in this high-risk group. Birth HIV DNA PCR results may fail to adequately identify all positive neonates timeously for very early initiation of antiretroviral treatment.

Dynamics and epigenetic signature of regulatory T-cells following antiretroviral therapy initiation in acute HIV infection.

BackgroundHIV infection promotes the expansion of immunosuppressive regulatory T-cells (Tregs), contributing to immune dysfunction, tissue fibrosis and disease progression. Early antiretroviral treatment (ART) upon HIV infection improves CD4 count and decreases immune activation. However, Treg dynamics and their epigenetic regulation following early ART initiation remain understudied.MethodsTreg subsets were characterized by flow cytometry in 103 individuals, including untreated HIV-infected participants in acute and chronic phases, ART-treated in early infection, elite controllers (ECs), immunological controllers (ICs), and HIV-uninfected controls. The methylation status of six regulatory regions of the foxp3 gene was assessed using MiSeq technology.FindingsTotal Treg frequency increased overtime during HIV infection, which was normalized in early ART recipients. Tregs in untreated individuals expressed higher levels of activation and immunosuppressive markers (CD39, and LAP(TGF-β1)), which remained unchanged following early ART. Expression of gut migration markers (CCR9, Integrin-β7) by Tregs was elevated during untreated HIV infection, while they declined with the duration of ART but not upon early ART initiation. Notably, gut-homing Tregs expressing LAP(TGF-β1) and CD39 remained higher despite early treatment. Additionally, the increase in LAP(TGF-β1)+ Tregs overtime were consistent with higher demethylation of conserved non-coding sequence (CNS)-1 in the foxp3 gene. Remarkably, LAP(TGF-β1)-expressing Tregs in ECs were significantly higher than in uninfected subjects, while the markers of Treg activation and gut migration were not different.InterpretationEarly ART initiation was unable to control the levels of immunosuppressive Treg subsets and their gut migration potential, which could ultimately contribute to gut tissue fibrosis and HIV disease progression.FundingThis study was funded by the Canadian Institutes of Health Research (CIHR, grant MOP 142294) and in part by the AIDS and Infectious Diseases Network of the Réseau SIDA et maladies infectieuses du Fonds de recherche du Québec-Santé (FRQ-S).

Normalization of B Cell Subsets but Not T Follicular Helper Phenotypes in Infants With Very Early Antiretroviral Treatment.

Introduction: Infant HIV-1-infection is associated with high morbidity and mortality if antiretroviral treatment (ART) is not initiated promptly. We characterized development of circulating T follicular helper cells (cTfh) and their relationship to naïve/memory B cell subsets in a cohort of neonates initiating ART within the first week of life.Methods: Infants were diagnosed within 48 hours of birth and started ART as soon as possible. The frequency and phenotype of cTfh and B cells were analyzed at enrollment (birth −19 days) and at 4, 12, and 72 weeks of age in blood of 27 HIV-1-intrauterine-infected and 25 HIV-1 exposed uninfected (HEU) infants as part of a study in Johannesburg, South Africa. cTfh cells were divided into Tfh1, Tfh2, and Tfh17 subsets. B cell phenotypes were defined as naïve, resting memory, activated memory and tissue-like memory cells.Results: HIV-1-infected infants had higher frequencies of cTfh cells than HEU infants up to 12 weeks of age and these cTfh cells were polarized toward the Tfh1 subset. Higher frequencies of Tfh1 and lower frequencies of Tfh2 and Tfh17 correlated with lower CD4+ T cell percentages. Lower frequencies of resting memory, with corresponding higher frequencies of activated memory B cells, were observed with HIV-1 infection. Importantly, dysregulations in B cell, but not cTfh cell, subsets were normalized by 72 weeks.Conclusion: Very early ART initiation in HIV-1-infected infants normalizes B cell subsets but does not fully normalize perturbations in cTfh cell subsets which remain Tfh1 polarized at 72 weeks. It remains to be determined if very early ART improves vaccine antibody responses despite the cTfh and B cell perturbations observed over the time course of this 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.

Rhodococcus infection in HIV infected patients: Clinical presentation and diagnoses

Background: Rhodococcus Equi is a gram positive coryneform bacterium that causes zoonotic infections in the animal kingdom and ias been reported in immunocompromised humans as emerging opportunistic pathogens. Methods & Materials: Retrospective review of patients electronic records from y 2006 to 2011, that were microbiologically confirmed rhodococcus equi infection. Results: A total of 26 patients were HIV positive with a median CD4 ount of 14 cells/ul.Mode of hiv transmission were 40.7% injecting drug use (11 patients), 51.7% sexual contact and 7.6% were unknown. None of the patients had a known history of contact with any animal sources for rhodococcus. 70.4%(19) patients were antiretroviral naïve at the time of presentation, 48%(13) patients had other concurrent AIDS defining illnesses. Pulmonary involvement with confirmed bacteraemia was seen in 77.8% (21) cases.18.5% (5) had primary bacteraemia with no other source of infection. One patient had isolated right suppurative lymphadenitis. Cavitatory pneumonia were seen in majority of the cases. In comparison to the available literature data, we saw a similar sensitivity pattern for most of our isolates with a resistance towards penicillin and ampicillin. Most patients were treated with a combination of antibiotics Conclusion: Increase awareness of rhodococcus infection as an opportunistic pathoegn,prompt microbiological diagnosis and combined antimicrobial treatment seem to be the cornerstone pf effective treatment. Early initiation of antiretroviral treatment and adherence seem to be necessary to improve outcome.

Early ART Initiation Improves HIV Status Disclosure and Social Support in People Living with HIV, Linked to Care Within a Universal Test and Treat Program in Rural South Africa (ANRS 12249 TasP Trial).

We investigated the effect of early antiretroviral treatment (ART) initiation on HIV status disclosure and social support in a cluster-randomized, treatment-as-prevention (TasP) trial in rural South Africa. Individuals identified HIV-positive after home-based testing were referred to trial clinics where they were invited to initiate ART immediately irrespective of CD4 count (intervention arm) or following national guidelines (control arm). We used Poisson mixed effects models to assess the independent effects of (a) time since baseline clinical visit, (b) trial arm, and (c) ART initiation on HIV disclosure (n=182) and social support (n=152) among participants with a CD4 count>500 cells/mm3 at baseline. Disclosure and social support significantly improved over follow-up in both arms. Disclosure was higher (incidence rate ratio [95% confidence interval]: 1.24 [1.04; 1.48]), and social support increased faster (1.22 [1.02; 1.46]) in the intervention arm than in the control arm. ART initiation improved both disclosure and social support (1.50 [1.28; 1.75] and 1.34 [1.12; 1.61], respectively), a stronger effect being seen in the intervention arm for social support (1.50 [1.12; 2.01]). Besides clinical benefits, early ART initiation may also improve psychosocial outcomes. This should further encourage countries to implement universal test-and-treat strategies.

Immunological and virological efficacy of different antiretroviral regimens initiated during acute/recent HIV infection.

Antiretroviral treatment (ART) during acute/recent HIV infection decreases transmission and optimizes immune recovery but the optimal ART-regimen in this setting is unknown. The objectives were to analyze the virological efficacy, immunological reconstitution and tolerability of different ART-regimens at 3 years after starting ART during acute/recent HIV infection. Retrospective cohort study of consecutive acutely/recently infected patients who started ART within 6 months postinfection. We compared regimens based on protease-inhibitors (N = 28), integrase-strand-transfer-inhibitors (InSTI, N = 87) and nonnucleoside-reverse-transcriptase-inhibitors (N = 22). Virological suppression (viral load <50 copies/ml), immune reconstitution (CD4 T-cell count >900 cells/μl and CD4/CD8 ratio >1) and adverse events leading to ART discontinuation at 1 and 3 years were compared. Baseline characteristics were comparable among groups. Overall viral suppression at 1 (96%) and 3 years (99%) was comparable in all ART regimens and, InSTI group, comparable for dolutegravir and elvitegravir within InSTIs. CD4 T-cell counts at 1 year were comparable in all ART regimens. Overall proportion of patients reaching CD4 cell count more than 900 cells/μl and CD4/CD8 ratio more than 1 was 36% and 40% and 46% and 63% at 1 and 3 years, respectively with no differences among ART regimens. Starting ART during the earliest Fiebig stages (I-V vs. VI) was associated with higher rates of CD4 cell count more than 900 cells/μl at 3 years (P = 0.027). Discontinuation due to adverse events was more frequent with nonnucleoside-reverse-transcriptase-inhibitors compared with other ART classes. Viral suppression and immunological recovery were excellent, with no differences between ART regimens. Earlier ART initiation was associated with a higher proportion of long-term immunological recovery.

Effect of the Timing of Antiretroviral Treatment Initiation on Outcomes in Children Living With Human Immunodeficiency Virus Admitted With Severe Acute Malnutrition.

Delays in early infant diagnosis and antiretroviral treatment (ART) initiation in developing countries frequently result in malnutrition at initial presentation with associated higher mortality and delayed immune recovery. The optimal timing of ART initiation is yet to be established. Eighty-two children admitted with HIV and severe acute malnutrition (SAM) between July 2012 and December 2015 were enrolled. Patients were randomized to initiate ART within 14 days from admission (early arm) or delay ART initiation until nutritional recovery and >14 days after admission (delayed arm). All patients received a standardized treatment and feeding protocol and were followed to 48 weeks. The mean age of the patients at baseline was 23.3 months (standard deviation [SD], 27.9; range, 1.6-129 months). The mean time from admission to ART initiation was 5.6 days (SD, 4.4) in the early arm and 23 days (SD, 5.8) in the delayed arm (P < .001). There was no significant difference in mortality (P = .62), virologic response (P = .53), and anthropometric response (P = .57) between the 2 groups at 48 weeks. However, the rates of change in CD4, viral load, weight for age z score, and height for age z score occurred earlier and favored the delayed arm at early time points but were not significant at 24 and 48 months. Despite initial improved responses in the delayed arm, lack of difference in outcome at 48 weeks supports a pragmatic approach with earlier ART initiation in children living with HIV admitted with SAM.In this randomised controlled study of ART initiation in children admitted with HIV and severe acute malnutrition (SAM), despite initial improved responses in the delayed arm, lack of difference in outcome at 48 weeks supports a pragmatic approach with earlier ART initiation in children living with HIV admitted with SAM. PACTR 21609001751384.

Impact of Early Antiretroviral Treatment Initiation on Performance of Cross-Sectional Incidence Assays.

Antiretroviral therapy (ART) can impact assays used for cross-sectional HIV incidence testing, causing inaccurate HIV incidence estimates. We evaluated the relationship between the timing of ART initiation and the performance of two serologic HIV incidence assays. We analyzed 302 samples from 55 individuals from the RV217 cohort (Early Capture HIV Cohort Study). Participants were grouped by ART start time: ART started <1 year after infection (N = 9); ART started 1-3 years after infection (N = 12); and never received ART (N = 34). Samples were tested using the Sedia LAg-Avidity and Johns Hopkins modified Bio-Rad-Avidity assays. Results were compared with those from the Johns Hopkins HIV Cohort in which participants initiated ART an average of 10 years after infection (N = 17). Participants on ART were virally suppressed at the time of sample collection. The increase in normalized optical density (ODn) values was an average of 2.15 U/year lower in participants who started ART <1 year after infection than in those who did not start ART. Participants who started ART 1-3 years after infection had a decline in ODn values 0.90 U/year faster compared with those who started ART an average of 10 years after infection. Timing of ART initiation did not significantly impact results obtained with the Bio-Rad-Avidity assay. ART initiation <1 year after HIV infection was associated with persistently low limiting antigen (Lag)-Avidity values; this could lead to overestimation of HIV incidence. LAg-Avidity values declined more rapidly the earlier ART was initiated. Bio-Rad-Avidity values were not impacted by the timing of ART initiation.

Neural correlates of maintenance working memory, as well as relevant structural qualities, are associated with earlier antiretroviral treatment initiation in vertically transmitted HIV.

There is evidence of HIV affecting cognitive functioning across age groups, with adult studies showing related deficits in frontostriatal and hippocampal regional activity. Additionally, delayed initiation of antiretroviral treatment (ART) has been associated with poorer cognitive outcomes in HIV-infected youth. Little is known, however, of the neural correlates underlying such cognitive deficits in youth populations. We investigated maintenance working memory-related brain activity in South African HIV-infected youth and controls, and the effect of ART initiation age on underlying structures. Sixty-four perinatally infected youth (ages 9-12) and 20 controls (ages 9-13) underwent functional magnetic resonance imaging (fMRI) while completing 1-back and 0-back blocks of the N-back task. At an uncorrected p value threshold of 0.001, the HIV-infected group showed decreased activation in the left superior temporal gyrus, pre- and postcentral gyri, insula, and putamen as well as bilateral hippocampus, and mid cingulum. The HIV patients with delayed ART initiation showed less activation during processing conditions in the mid cingulum; left inferior parietal gyrus; and right inferior frontal, bilateral thalamic, and superior temporal regions. When these regions were tested for structural differences, the mid cingulum and right inferior frontal gyrus, insula, and thalamus were found to have less cortical thickness, surface area, or volume in the group with delayed ART initiation. Regional differences between HIV-infected youth and controls noted in the N-back task are consistent with impairments in structures involved in maintenance working memory. These data support earlier ART initiation in perinatally infected individuals.

Tuberculosis Antigen-Specific T-Cell Responses During the First 6 Months of Antiretroviral Treatment.

The reconstitution of Mycobacterium tuberculosis antigen-specific CD4 T cells in a cohort of HIV-infected persons starting antiretroviral treatment (ART) in a high tuberculosis endemic area is described. Restoration of the antigen-specific CD4 T-cell subsets mirrored the overall CD4 T-cell compartment. Activation (assessed by HLA-DR expression) decreased during ART but remained elevated compared to HIV-uninfected persons. Despite known M. tuberculosis sensitization determined by interferon-γ release assay, 12/23 participants had no M. tuberculosis-specific CD4 T cells detectable by flow cytometry, combined with overall elevated T-cell activation and memory differentiation, suggesting heightened turnover. Our data suggest early ART initiation to maintain polyfunctional immune memory responses.