Early Antiretroviral Treatment Research Articles

Assessing the impact of autologous neutralizing antibodies on rebound dynamics in postnatally SHIV-infected ART-treated infant rhesus macaques.

The presence of antibodies against HIV in infected children is associated with a greater capacity to control viremia in the absence of therapy. While the benefits of early antiretroviral treatment (ART) in infants are well documented, early ART may interfere with the development of antibody responses. In contrast to adults, early treated children lack detectable HIV-specific antibodies, suggesting a fundamental difference in HIV pathogenesis. Despite this potential adverse effect, early ART may decrease the size of the latent reservoir established early in infection in infants, which can be beneficial in viral control. Understanding the virologic and immunologic aspects of pediatric HIV is crucial to inform innovative targeted strategies for treating children living with HIV. In this study, we investigate how ART initiation time sets the stage for trade-offs in the latent reservoir establishment and the development of humoral immunity and how these, in turn, affect posttreatment dynamics. We also elucidate the biological function of antibodies in pediatric HIV. We employ mathematical modeling coupled with experimental data from an infant nonhuman primate Simian/Human Immunodeficiency Virus (SHIV) infection model. Infant Rhesus macaques (RMs) were orally challenged with SHIV.C.CH505 375H dCT four weeks after birth and started treatment at different times after infection. In addition to viral load measurements, antibody responses and latent reservoir sizes were measured. We estimate model parameters by fitting viral load measurements to the standard HIV viral dynamics model within a nonlinear fixed effects framework. This approach allows us to capture differences between rhesus macaques (RMs) that develop antibody responses or exhibit high latent reservoir sizes compared to those that do not. We find that neutralizing antibody responses are associated with increased viral clearance and decreased viral infectivity but decreased death rate of infected cells. In addition, the presence of detectable latent reservoir is associated with less robust immune responses. These results demonstrate that both immune response and latent reservoir dynamics are needed to understand post-rebound dynamics and point to the necessity of a comprehensive approach in tailoring personalized medical interventions.

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.

Antiretroviral treatment for HIV infection and AIDS

Background: Antiretroviral therapy is the cornerstone treatment for people living with human immunodeficiency virus (HIV). Clinical practice guidelines for antiretroviral therapy have been developed.Current Concepts: After the introduction of zidovudine, more than 30 antiretroviral agents have been approved for the treatment of HIV infection. Since a controlled trial proved the efficacy and safety of combination antiretroviral therapy, virologic suppression, immune reconstitution, and long-term survival of people living with HIV have been achievable goals. Early antiretroviral treatment for all people living with HIV is an effective strategy to maintain individual health and prevent the transmission of HIV infection. Selecting an appropriate combination antiretroviral therapy requires careful consideration of various factors, including regimen characteristics, pretreatment viral load and CD4+ cell counts, comorbid conditions, and the anticipated level of compliance. Ongoing advances in antiretroviral treatment, such as the development of long-acting injectables and medications targeting multidrug-resistant HIV, address challenges in the treatment of HIV infection.Discussion and Conclusion: Although cure of HIV infection is impossible with current antiretroviral treatment, HIV infection has become a chronic disease with long-term survival. Hence, clinicians should have knowledge of antiretroviral treatment guidelines.

Cytomegalovirus infection among people living with HIV in Sweden: Case profiles, treatment strategies and patient outcomes at Karolinska University Hospital 2010-2020.

In countries with access to early antiretroviral treatment (ART), opportunistic infections caused by cytomegalovirus (CMV) in people living with HIV (PLWH) are becoming increasingly rare. As potential complications are severe, it is critical to remain aware of this important diagnosis. However, clinical characteristics and prognosis of CMV infection in PLWH in the era of modern ART have not been well described. Here, we compiled the clinical presentation, management and outcome of CMV infection in PLWH treated at the infectious diseases clinic of Karolinska University Hospital during 2010-2020. We identified 51 cases of active CMV infection, based on detection of CMV-DNA, mainly diagnosed in patients with CD4 T-cell count <200 cells/μL (86%). Median time from HIV diagnosis to detection of CMV infection was 16 days. In 20 cases (39%), CMV infection was symptomatic with retinitis identified as a manifestation in 70% of cases. Symptomatic CMV infection was treated for 73 (20-313) days upon diagnosis, mostly using valganciclovir. One-year mortality was 22% and was associated with longer time to ART initiation from HIV diagnosis and with comorbidities, but not with CMV-DNA levels or CD4 count. Immune reconstitution was not significantly compromised in patients with symptomatic CMV, although CD4/8 ratio tended to be lower in patients with systemic CMV infection. Retinitis remains the most common manifestation of symptomatic CMV infection in PLWH. Recognizing CMV infection is important, especially in the management of 'late presenters'. Adequate duration of antiviral therapy and appropriate follow-up must be ensured to avoid complications.

Therapeutic effectiveness on early and delayed treatment of antiretroviral in TB-HIV patients: a literature review

Introduction: Indonesia is one of the countries with a high TB-HIV prevalence. Antiretroviral treatment (ART) is only being administered to approximately 42% of TB-HIV patients. The low utilization of ART can be attributed, in part, to the delayed initiation of treatment. Nonetheless, starting ART in these people at an early stage poses risks, owing to the increased likelihood of drug-drug interactions and the manifestation of Immune Reconstitution Inflammatory Syndrome (IRIS) side effects when combined with anti-TB medication. Postponing ART, on the other hand, can hasten illness progression and increase the risk of death. Methods: A literature review was conducted to assess the effects of early ART (within four weeks of getting anti-TB) against delayed ART initiation (at least eight weeks after receiving anti-TB) in individuals co-infected with TB and HIV. The data was obtained by a comprehensive electronic search using the PubMed and Science Direct databases. Results: The findings of our study suggest that there was no statistically significant disparity in mortality rates between the early ART group and the delayed ART group. The initial ART cohort had a markedly elevated susceptibility to encountering an IRIS occurrence, particularly among individuals with a CD4 count below 50 cells per cubic millimeter. Conclusion: In summary, the strategy of delaying the initiation of ART in patients co-infected with TB-HIV is seen as preferable when compared to the approach of early treatment. The frequency of IRIS events is a significant determinant in determining the optimal timing of ART initiation in individuals co-infected with TB-HIV.

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.

Demographics of Youth With Newly Diagnosed Acute/Recent HIV Infection in Adolescent Trials Network 147: Early Treatment of Acute HIV Infection

PurposeGay, bisexual, and other cisgender men who have sex with men, and racial minority youth are at elevated risk of acquiring HIV infection. The Adolescent Trials Network 147 recruited youth with acute/recent HIV-infection for early antiretroviral treatment. The cohort make-up is described here. MethodsTreatment-naïve, recently identified HIV + youth, aged 12–24 years, from Los Angeles and New Orleans were recruited from community centers, clinics, social media, and a high-risk seronegative cohort (n = 1,727, the Adolescent Trials Network 149) using point-of-care assays. Acute HIV infection was determined by Fiebig staging. HIV RNA viral load (VL) and CD4 cell counts, along with demographic and behavioral data were assessed at enrollment. ResultsBetween July 2017 and July 2021, 103 newly diagnosed youth were enrolled, initiating antiretroviral treatment within a week. Mean age was 20.8 years (standard deviation: 2.4); 90.3% identified as cis male, 83.5% were single or in casual relationships, 71.8% were gay, bisexual, and other cisgender men who have sex with men; 60.2% were Black. One-fourth (24.3%) reported homelessness ever; 10.7% within last 4 months. At enrollment, median plasma VL was 37,313 HIV RNA copies/ml (interquartile range: 5,849–126,162) and median CD4 count 445.5 cells/mm3 (interquartile range: 357–613). 40% of youth reported acute retroviral symptoms before or at enrollment. Acutely infected, seroconverting youth had the highest VL. Sexually transmitted coinfections were present at enrollment in 56% of the cohort, with syphilis being most frequent (39%). DiscussionEarly identification and treatment of HIV can increase positive HIV outcomes. A high sexually transmitted infection burden was present in recently HIV-infected youth. Acute retroviral symptoms were not reported by most participants, demonstrating that broad universal HIV screening is needed for identification of recent infection in youth.

Broadly neutralizing antibodies: "The next thing" to treat children with HIV?

Monthly treatment with two neutralizing antibodies maintained HIV suppression in almost half of children who received early antiretroviral treatment (Shapiro etal.).

HIV Never Sleeps: Evidence to Support Early Antiretroviral Treatment.

This Pillars of Immunology article is a commentary on “HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease,” a pivotal article written by G. Pantaleo, C. Graziosi, J. F. Demarest, L. Butini, M. Montroni, C. H. Fox, J. M. Orenstein, D. P. Kotler, and A. S. Fauci, and published in Nature, in 1993. https://www.nature.com/articles/362355a0. The Journal of Immunology, 2023, 210: 1181–1182

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.

Cost-effectiveness of broadly neutralizing antibody prophylaxis for HIV-exposed infants in sub-Saharan African settings.

Infant HIV prophylaxis with broadly neutralizing anti-HIV antibodies (bNAbs) could provide long-acting protection against vertical transmission. We sought to estimate the potential clinical impact and cost-effectiveness of hypothetical bNAb prophylaxis programmes for children known to be HIV exposed at birth in three sub-Saharan African settings. We conducted a cost-effectiveness analysis using the CEPAC-Pediatric model, simulating cohorts of infants from birth through death in Côte d'Ivoire, South Africa and Zimbabwe. These settings were selected to reflect a broad range of HIV care cascade characteristics, antenatal HIV prevalence and budgetary constraints. We modelled strategies targeting bNAbs to only WHO-designated "high-risk" HIV-exposed infants (HR-HIVE) or to all HIV-exposed infants (HIVE). We compared four prophylaxis approaches within each target population: standard of care oral antiretroviral prophylaxis (SOC), and SOC plus bNAbs at birth (1-dose), at birth and 3 months (2-doses), or every 3 months throughout breastfeeding (Extended). Base-case model inputs included bNAb efficacy (60%/dose), effect duration (3 months/dose) and costs ($60/dose), based on published literature. Outcomes included paediatric HIV incidence and incremental cost-effectiveness ratios (ICERs) calculated from discounted life expectancy and lifetime HIV-related costs. The model projects that bNAbs would reduce absolute infant HIV incidence by 0.3-2.2% (9.6-34.9% relative reduction), varying by country, prophylaxis approach and target population. In all three settings, HR-HIVE-1-dose would be cost-saving compared to SOC. Using a 50% GDP per capita ICER threshold, HIVE-Extended would be cost-effective in all three settings with ICERs of $497/YLS in Côte d'Ivoire, $464/YLS in South Africa and $455/YLS in Zimbabwe. In all three settings, bNAb strategies would remain cost-effective at costs up to $200/dose if efficacy is ≥30%. If the bNAb effect duration were reduced to 1 month, the cost-effective strategy would become HR-HIVE-1-dose in Côte d'Ivoire and Zimbabwe and HR-HIVE-2-doses in South Africa. Findings regarding the cost-effectiveness of bNAb implementation strategies remained robust in sensitivity analyses regarding breastfeeding duration, maternal engagement in postpartum care, early infant diagnosis uptake and antiretroviral treatment costs. At current efficacy and cost estimates, bNAb prophylaxis for HIV-exposed children in sub-Saharan African settings would be a cost-effective intervention to reduce vertical HIV transmission.

"There Are Just Too Many Rooms Here!" Perception of Clients and Health Care Workers on the Implementation of Test and Treat Strategy at Area 25 Health Center in Lilongwe, Malawi.

Background: Malawi adopted World Health Organisation test-and-treat policy in 2016. The policy initiates early antiretroviral treatment to all clients diagnosed with HIV, irrespective of their CD4 count. However, some facilities record low linkage following the strategy. Perceptions of clients and health care workers on the implementation of test-and-treat strategy were explored in Malawi. Methods: A descriptive qualitative approach was conducted in which 21 in-depth interviews, 9 key informant interviews, and 15 non-participatory observations were conducted. Data were analyzed following thematic approach. Results: Most participants had positive perceptions of the test-and-treat strategy. However, negative perceptions stemmed from the fragmented structure of the facility with multiple rooms in which the client navigates through as well as limited privacy. Conclusion: Optimal implementation of the test-and-treat strategy will need to strengthen privacy and minimize unintended disclosure that is inherent in the organization of services.

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.

The effect of antiretroviral therapy initiation on vitamin D levels and four oral diseases among Kenyan children and adolescents living with HIV.

ObjectivesThe impact of antiretroviral treatment (ART) on the occurrence of oral diseases among children and adolescents living with HIV (CALHIV) is poorly understood. The aim of this study was to determine the effect of ART timing on vitamin D levels and the prevalence of four oral diseases (dry mouth, dental caries, enamel hypoplasia, and non-herpes oral ulcer) among Kenyan CALHIV from two pediatric HIV cohorts.MethodsThis nested cross-sectional study was conducted at the Kenyatta National Hospital, Nairobi, Kenya. CALHIV, 51 with early-ART initiated at <12 months of age and 27 with late-ART initiated between 18 months-12 years of age, were included. Demographics, HIV diagnosis, baseline CD4 and HIV RNA viral load data were extracted from the primary study databases. Community Oral Health Officers performed oral health examinations following standardized training.ResultsAmong 78 CALHIV in the study, median age at the time of the oral examination was 11.4 years old and median ART duration at the time of oral examination was 11 years (IQR: 10.1, 13.4). Mean serum vitamin D level was significantly higher among the early-ART group than the late-ART group (29.5 versus 22.4 ng/mL, p = 0.0002). Children who received early-ART had a 70% reduction in risk of inadequate vitamin D level (<20 ng/mL), compared to those who received late-ART (p = 0.02). Although both groups had similar prevalence of oral diseases overall (early-ART 82.4%; late-ART 85.2%; p = 0.2), there was a trend for higher prevalence of dry mouth (p = 0.1) and dental caries (p = 0.1) in the early versus late ART groups. The prevalence of the four oral diseases was not associated with vitamin D levels (p = 0.583).ConclusionsAfter >10 years of ART, CALHIV with early-ART initiation had higher serum vitamin D levels compared to the late-ART group. The four oral diseases were not significantly associated with timing of ART initiation or serum vitamin D concentrations in this cohort. There was a trend for higher prevalence of dry mouth and dental caries in the early-ART group, probably as side-effects of ART.

Thirteen cancers associated with HIV infection in a Black South African cancer patient population (1995-2016).

South Africa's HIV epidemic has evolved over time in terms of numbers of people living with HIV, access to antiretroviral treatment (ART) and age. These changes have profoundly influenced local cancer patterns. The Johannesburg Cancer Study has, over a period of 22 years (1995-2016), recruited over 20 000 incident black cancer patients who consented to provide answers to a questionnaire and blood samples (serum, DNA). This has presented a unique opportunity to examine the evolving association of HIV with cancer in Africa. We used logistic regression models to explore case-control associations between specific cancers and HIV, using participants with non-infection related cancers as controls. Using data of 20 835 cancer patients with confirmed HIV status, we found the following cancers to be associated with HIV: Kaposi's sarcoma (ORadj ; 95%CI): (99.1;72.6-135.1), non-Hodgkin lymphoma (11.3;9.3-13.6), cervical cancer (2.7;2.4-3.0), Hodgkin lymphoma (3.1;2.4-4.2), cancer of the eye/conjunctiva (18.7;10.1-34.7), anogenital cancers (anus [2.1;1.4-3.2], penis [5.4;2.7-10.5], vulva [4.8;3.5-6.4], vagina [5.5;3.0-10.2]), oropharyngeal cancer (1.6;1.3-1.9), squamous cell carcinoma of the skin (3.5;2.4-4.9), melanoma (2.0;1.2-3.5) and cancer of the larynx (1.7;1.3-2.4). Kaposi's sarcoma odds ratios increased from the pre-ART (1995-2004) to the early ART (2005-2009) period but declined in the late ART (2010-2016) period. Odds ratios for cancers of the eye/conjunctiva, cervix, penis and vulva continued to increase in recent ART periods. Our study confirms the spectrum of HIV-associated cancers found in other African settings. The odds ratios of conjunctival and HPV-related cancers continue to rise in the ART era as the HIV positive population ages.

Infants Receiving Very Early Antiretroviral Therapy Have High CD4 Counts in the First Year of Life.

NCT02140255.

The cost of providing hospital-based (early) antiretroviral treatment in Indonesia: what has changed in almost a decade?

ABSTRACT 17% of all people living with HIV in Indonesia who are in need of antiretroviral treatment (ART) actually receive the treatment. The cost of ART based on three CD4 cell count groups (e.g., 0–200, 201–350, >350 cells/mm3) in a main referral hospital in West Java, Indonesia, in 2011–2016 was compared to the results from a decade earlier in the same setting. Costs were estimated including resources used for opportunistic infection treatment, laboratory tests, and antiretroviral (ARV) drugs. For each group, we divided the costs into several periods: pre-ART, and every 6 months up to 24 months after onset of treatment. Before ART, costs were dominated by laboratory tests (>80%); ARV drugs were the main cost after treatment onset (>92%). Average cost of treatment per year was US$600 across all groups. Moreover, the patient cost to access ART (n = 49 patients) did not exceed 10% of their household monthly expenditures (i.e., 4%). The unit cost of providing ART per patient/year is half the cost under the previous treatment initiation guidelines. A lower ARV drug cost, more patients in higher CD4 cell-count groups, and lower viral load test cost characterize the current cost profile.

Time of the First Antiretroviral Treatment (ART) Default and Factors Associated to Early ART Default in the Test and Treat Context: Evidence from the West region of Cameroon

Antiretroviral Treatment (ART) retention continues to be a challenge in Sub-Saharan Africa. Understanding factors that contribute to default at the early stage of ART can contribute to avoid poor treatment outcomes. We conducted a retrospective cross-sectional study on adult patients who initiated ART treatment between October 2019 and September 2020 in 25 health facilities in the West region of Cameroon. Early ART default was defined as having default within the first three months of treatment. The mean age of the 2219 clients included in the analysis was 36.8 (SD:13.4), and 838 (36.5%) were male. The median time to the first ART default of the 629 (28.3%) participants who experienced at least one ART default within 12 months after their ART initiation was 5 months, and 41.2% of those defaults occurred within the first three months of ART. Male gender (AOR =1.3; 95%CI:1.1-1.7) and good health at initiation (AOR =1.7; 95%CI:1.3-2.2) were associated with a high risk of early default; while being followed up in a private facility (AOR =0.3; 95%CI:0.2-0.6) were associated with less risk of early default. The ART default at the early stage of HIV care is high in the West region of Cameroon and more frequent in the male gender and in patients with apparent good health at the time of ART initiation. Interventions should be identified and implemented to ensure continuity of ART treatment especially in males, in clients with good health at the time of ART initiation, and in clients on care in public health facilities.

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.

MiRNA Profile Based on ART Delay in Vertically Infected HIV-1 Youths Is Associated With Inflammatory Biomarkers and Activation and Maturation Immune Levels.

Early antiretroviral treatment (ART) in vertically acquired HIV-1-infection is associated with a rapid viral suppression, small HIV-1 reservoir, reduced morbimortality and preserved immune functions. We investigated the miRNA profile from vertically acquired HIV-1-infected young adults based on ART initiation delay and its association with the immune system activation. Using a microRNA panel and multiparametric flow cytometry, miRNome profile obtained from peripheral blood mononuclear cells and its association with adaptive and innate immune components were studied on vertically HIV-1-infected young adults who started ART early (EARLY, 0-53 weeks after birth) and later (LATE, 120-300 weeks). miR-1248 and miR-155-5p, were significantly upregulated in EARLY group compared with LATE group, while miR-501-3p, miR-548d-5p, miR-18a-3p and miR-296-5p were significantly downregulated in EARLY treated group of patients. Strong correlations were obtained between miRNAs levels and soluble biochemical biomarkers and immunological parameters including CD4 T-cell count and maturation by CD69 expression on CD4 T-cells and activation by HLA-DR on CD16high NK cell subsets for miR-1248 and miR-155-5p. In this preliminary study, a distinct miRNA signature discriminates early treated HIV-1-infected young adults. The role of those miRNAs target genes in the modulation of HIV-1 replication and latency may reveal new host signaling pathways that could be manipulated in antiviral strategies. Correlations between miRNAs levels and inflammatory and immunological markers highlight those miRNAs as potential biomarkers for immune inflammation and activation in HIV-1-infected young adults who initiated a late ART.