Early Human Immunodeficiency Virus Research Articles

Diagnosis of Human Immunodeficiency Virus Infection

Early diagnosis and early treatment of human immunodeficiency virus (HIV) infection are essential for clinical and public health benefits. Diagnostic algorithms for early diagnosis are being emphasized, and rapid tests at the point of care have been expanded to improve voluntary testing rates. Despite advances in laboratory diagnostic tests, early HIV infection can still be missed due to window periods, and it is crucial to recognize the limitations of testing methods and the potential for false negative and false positive results.

Clinical characteristics, diagnosis, treatment and outcomes of patients living with HIV and co-infected with tuberculosis and histoplasmosis: a 5-y retrospective case series.

In Latin America, tuberculosis (TB) and histoplasmosis are two of the most frequent opportunistic infections affecting people living with human immunodeficiency virus (HIV). However, there are limited data on the clinical characteristics and outcomes of patients with concurrent TB and histoplasmosis infections. This was a retrospective observational study to describe the clinical, epidemiological and laboratory characteristics and outcomes of 21 patients living with HIV (PLHIV) who were diagnosed with concurrent histoplasmosis and TB between 2017 and 2021 in Guatemala City, Guatemala. Most patients were male and were newly diagnosed with HIV. All patients had advanced HIV disease (AHD). They presented with a median CD4 count of 20cells/µl. The most common symptoms reported by the patients were fever, weight loss, cough and diarrhoea. Twelve patients died within 6months of baseline evaluation, for a mortality rate of 57.1%. PLHIV with concurrent TB and histoplasmosis infections are characterised by AHD, predominantly presenting with disseminated forms of these infections and with unspecific symptoms and signs. This evidence calls for early HIV and opportunistic infection screening and insights into the challenges and opportunities for the efficient diagnostic and therapeutic management of patients with AHD with concurrent histoplasmosis and TB infections.

Positivity rate, trend and associated risk factors of mother-to-child transmission of HIV among HIV-exposed infants

BackgroundMother-To-Child-Transmission (MTCT) of Human Immunodeficiency Virus (HIV) occurs during pregnancy, delivery and breastfeeding, and cause infection among several new-borns. However, there is limited recent evidence on the burden of MTCT of HIV in Ethiopia from a large-scale data. Thus, this study aimed to determine the positivity rate, trend and associated risk factors of MTCT among HIV-exposed infants.MethodologyA cross-sectional study was conducted among 5,679 infants whose specimen referred to Ethiopian Public Health Institute HIV referral laboratory for Early Infant Diagnosis (EID) from January 01, 2016, to December 31, 2020. Data were extracted from the national EID database. Frequencies and percentages were used to summarize the data on characteristics of infants. Logistic regression analysis was employed to identify factors associated with positivity rate of MTCT of HIV. Level of significance was set at 5%.ResultsThe mean age of the infants was 12.6 (± 14.6) weeks with an age range of 4 to 72 weeks. Half of the infants (51.4%) were female. The positivity rate of MTCT decreased from 2.9% in 2016 to 0.9% in 2020 with five-year average positivity rate of 2.6%. HIV test after six weeks (Adjusted odds ratio (AOR) = 2.7; 95% confidence interval (CI): (1.8–4.0,)); p < 0.001), absence of prevention of mother-to-child-transmission (PMTCT) service (AOR = 4.6; 95% CI: (2.9–7.4)); p = 0.001), nevirapine prophylaxis not received (AOR = 2.0; 95% CI: (1.3–3.2)); p < 0.001), and unknown ART status of the mother at delivery (AOR = 11; 95% CI: (5.5–22.1)); p < 0.001) were significantly associated with MTCT of HIV.ConclusionThe positivity rate of MTCT of HIV was showing declining tendency gradually in the study period. Strengthening PMTCT service, early HIV screening and starting ART for pregnant women, and early infant diagnosis are required to reduce the burden of HIV infection among infants exposed to HIV.

Gene dysregulation in acute HIV-1 infection - early transcriptomic analysis reveals the crucial biological functions affected.

Transcriptomic analyses from early human immunodeficiency virus (HIV) infection have the potential to reveal how HIV causes widespread and lasting damage to biological functions, especially in the immune system. Previous studies have been limited by difficulties in obtaining early specimens. A hospital symptom-based screening approach was applied in a rural Mozambican setting to enrol patients with suspected acute HIV infection (Fiebig stage I-IV). Blood samples were collected from all those recruited, so that acute cases and contemporaneously recruited, uninfected controls were included. PBMC were isolated and sequenced using RNA-seq. Sample cellular composition was estimated from gene expression data. Differential gene expression analysis was completed, and correlations were determined between viral load and differential gene expression. Biological implications were examined using Cytoscape, gene set enrichment analysis, and enrichment mapping. Twenty-nine HIV infected subjects one month from presentation and 46 uninfected controls were included in this study. Subjects with acute HIV infection demonstrated profound gene dysregulation, with 6131 (almost 13% of the genome mapped in this study) significantly differentially expressed. Viral load was correlated with 1.6% of dysregulated genes, in particular, highly upregulated genes involved in key cell cycle functions, were correlated with viremia. The most profoundly upregulated biological functions related to cell cycle regulation, in particular, CDCA7 may drive aberrant cell division, promoted by overexpressed E2F family proteins. Also upregulated were DNA repair and replication, microtubule and spindle organization, and immune activation and response. The interferome of acute HIV was characterized by broad activation of interferon-stimulated genes with antiviral functions, most notably IFI27 and OTOF. BCL2 downregulation alongside upregulation of several apoptotic trigger genes and downstream effectors may contribute to cycle arrest and apoptosis. Transmembrane protein 155 (TMEM155) was consistently highly overexpressed during acute infection, with roles hitherto unknown. Our study contributes to a better understanding of the mechanisms of early HIV-induced immune damage. These findings have the potential to lead to new earlier interventions that improve outcomes.

Vertical Transmission Rate of Human Immunodeficiency Virus Exposed Twin Pregnancies and Associated Factors in West Bengal, India: a Retrospective Cohort Study.

Twin pregnancies are often associated with adverse obstetric outcomes. The mother-to-child transmission of the human immunodeficiency virus (HIV) in twin pregnancies has been less explored. Therefore, the present study aimed to determine the risk of vertical transmission of HIV in HIV-exposed twin pregnancies compared with that of singleton pregnancies and to explore the associated factors. We conducted a retrospective cohort study involving 348 HIV-exposed babies (58 twins and 290 singletons) through a systematic sampling from the program database of West Bengal, India, from April 2016 to March 2021. HIV vertical transmission rates were compared between single and twin live births. The effects of factors such as maternal age, timing of maternal HIV diagnosis, duration of antiretroviral treatment, mode of delivery, birth weight, and the sex of the baby were determined. The HIV transmission rate for twin pregnancies (15.5%) was significantly higher than that for single live births (5.5%) (adjusted odds ratio [OR] = 3.38 [1.17-9.69]). Among twin deliveries, maternal HIV diagnosis during the intrapartum and postpartum period was associated with HIV transmission (crude OR = 11.0, [2.2-54.9]). Perinatal HIV transmission is more common in twin pregnancies and is associated with the time of detection of maternal HIV. Therefore, early HIV detection and additional antiretroviral regimens should be considered for twin pregnancies.

Residual Central Nervous System Immune Activation Is Not Prevented by Antiretroviral Therapy Initiated During Early Chronic HIV Infection.

Antiretroviral therapy (ART) initiated during acute infection can potentially impact the central nervous system (CNS) reservoir, but the differential long-term effects of ART initiation during early or late chronic infection are unknown. We included neuroasymptomatic people with human immunodeficiency virus (HIV) with suppressive ART initiated during chronic (>1 year since transmission) HIV with archived cerebrospinal fluid (CSF) and serum samples after 1 and/or ≥3 years of ART from a cohort study. CSF and serum neopterin was measured using a commercial immunoassay (BRAHMS, Germany). In total, 185 people with HIV (median, 79 [interquartile range, 55-128] months on ART) were included. A significant inverse correlation was found between CD4+ T-cell count and CSF neopterin only at baseline (r = -0.28, P = .002), but not after 1 (r = -0.026, P = .8) or ≥3 (r -0.063, P = .5) years of ART. No significant differences were seen in CSF or serum neopterin concentrations between different pretreatment CD4+ T-cell strata after 1 or ≥3 (median, 6.6) years of ART. In people with HIV initiating ART during chronic infection, occurrence of residual CNS immune activation was not correlated with pretreatment immune status, even when treatment was initiated at high CD4+ T-cell counts, suggesting that the CNS reservoir, once established, is not differentially affected by the timing of ART initiation during chronic infection.

Assessment of Dermatological Manifestations of HIV in Primary Care

Abstract: HIV infection continues to be a significant problem. Infected patients with HIV/AIDS were the first to show skin infections in the 1980s. It was projected that 35 million individuals would be infected with the Human Immunodeficiency Virus (HIV) in 2013. Before illnesses like diabetes and COPD, skin disorders were considered the 4th most common non-fatal disease burden globally in terms of years lost owing to disability. HIV-related skin disorders have a significant burden on society, have an adverse effect on the quality of life, and are directly linked to death. Pathophysiology of the disease is based mainly on understanding the pathology of the skin's immune system, as CD4 lymphocytes are considered the main key to the immunological response of the dermis and serve to inhibit autoimmune diseases and control infections. Hence, a massive decline is noticed in CD4 lymphocytes in patients diagnosed with HIV/AIDS, as mostly CD4 counts below 200 cells per cubic millimetre, which reveals the absence of immunity in the patients Because HIV-related skin problems are challenging to manage and might even reoccur more frequently than in immunocompetent people in the absence of immunological reconstitution with cART, managing them effectively presents unique challenges. Early detection of skin problems linked to HIV offers the chance for early HIV identification and cART introduction, potentially improving overall survivability. Additionally, in environments with low resources, attention is brought to opportunistic infections that are more likely to be fatal, and skin disorders may go unnoticed. This review aims to summarise current knowledge of pathophysiology, causes, and treatment of HIV-related skin disorders with the objective of more qualitative resources for further research, which contributes to better understanding and reveals the points that need further research. Keywords:,,,, ,

Adaptation to HLA-associated immune pressure over the course of HIV infection and in circulating HIV-1 strains.

Adaptation to human leukocyte antigen (HLA)-associated immune pressure represents a major driver of human immunodeficiency virus (HIV) evolution at both the individual and population level. To date, there has been limited exploration of the impact of the initial cellular immune response in driving viral adaptation, the dynamics of these changes during infection and their effect on circulating transmitting viruses at the population level. Capturing detailed virological and immunological data from acute and early HIV infection is challenging as this commonly precedes the diagnosis of HIV infection, potentially by many years. In addition, rapid initiation of antiretroviral treatment following a diagnosis is the standard of care, and central to global efforts towards HIV elimination. Yet, acute untreated infection is the critical period in which the diversity of proviral reservoirs is first established within individuals, and associated with greater risk of onward transmissions in a population. Characterizing the viral adaptations evident in the earliest phases of infection, coinciding with the initial cellular immune responses is therefore relevant to understanding which changes are of greatest impact to HIV evolution at the population level. In this study, we utilized three separate cohorts to examine the initial CD8+ T cell immune response to HIV (cross-sectional acute infection cohort), track HIV evolution in response to CD8+ T cell-mediated immunity over time (longitudinal chronic infection cohort) and translate the impact of HLA-driven HIV evolution to the population level (cross-sectional HIV sequence data spanning 30 years). Using next generation viral sequencing and enzyme-linked immunospot interferon-gamma recall responses to peptides representing HLA class I-specific HIV T cell targets, we observed that CD8+ T cell responses can select viral adaptations prior to full antibody seroconversion. Using the longitudinal cohort, we uncover that viral adaptations have the propensity to be retained over time in a non-selective immune environment, which reflects the increasing proportion of pre-adapted HIV strains within the Western Australian population over an approximate 30-year period.

Effects of early human immunodeficiency virus infection on cerebral white matter blood flow autoregulation.

Blood flow autoregulation in cerebral white matter was measured before and after acute nicardipine-induced changes in mean arterial pressure of 10-21% in 21 treatment naïve HIV-positive adults and 32 controls. The autoregulatory index (-% cerebral blood flow change/% mean arterial pressure change) was not different at baseline ( P = 0.71) or after 1 year of treatment ( n = 11, P = 0.17). We found no autoregulatory defect to explain the increased stroke risk or the development of cerebral white damage in people with HIV.

HIV prevalence and associated factors among female sex workers in Iran: a bio-behavioral survey in 2020.

Despite the overall decline in human immunodeficiency virus (HIV) prevalence, it remains unacceptably high in key populations. This study aimed to estimate prevalence of HIV infection and high-risk behaviors among female sex workers (FSWs). This study was a cross-sectional survey of FSWs conducted between December 2019 and August 2020 in eight geographically diverse cities in Iran. After providing informed consent, participants completed a bio-behavioral questionnaire and after completion of the interview, rapid diagnostic tests (RDT) and dried blood spots (DBS) were collected to determine HIV and syphilis status as per national guidelines, if the women consented. All analyzes were based on RDS adjustment. Weighting was done according to Giles’SS estimator. Among the 1515 FSWs, the overall prevalence of HIV and syphilis were 1.6% (95% CI: 0.8–2.3) and zero, respectively. The highest HIV prevalence was observed in Shiraz (5.1%) and Khorramabad city (1.6%). In addition, HIV-positive FSWs had a higher mean age at first sexual contact than HIV-negative FSWs (21.4 ± 5.6 vs. 17.2 ± 4.2 years). Injection drug use and a history of arrest or incarceration were associated with an increased odds of HIV infection (OR = 6.25; 95% CI: 1.90-20.55 and OR = 4.57; 95% CI: 1.64–12.72, respectively). Based on the results, strategies to improve early HIV diagnosis, harm reduction, and use of testing and treatment strategies are needed to reduce and control HIV infections.

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.

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.

Analyses of Kaposi Sarcoma trends among adults establishing initial outpatient HIV care in Nigeria: 2006\u20132017

BackgroundThe incidence of Human Immunodeficiency Virus (HIV)-associated Kaposi Sarcoma (KS) in the pre-antiretroviral therapy (ART) population remains high in several countries in sub-Saharan Africa. We examined trends of KS prevalence in adults, establishing initial outpatient HIV care from 2006 to 2017 in Nigeria.MethodsWe analyzed data of 16,431 adults (age ≥ 18 years) enrolled for HIV care from January 1, 2006, to December 31, 2017, in a large clinic in Jos, Nigeria. KS at enrollment was defined as KS recorded in the electronic health record within 30 days of clinic enrollment. Time trends were compared among four periods: 2006–2008, 2009–2011, 2012–2014, and 2015–2017 using logistic regression models. Annual trends were analyzed using join point regression and restricted splines.ResultsThe study population had a mean age 35.1 (standard deviation, SD 9.5) years, and were 65.7% female (n = 10,788). The mean CD4 cell count was 220 (95% CI 117–223). The overall KS prevalence at entry was 0.59% (95% CI 0.48–0.72). Compared to 2006–2008, KS prevalence was significantly higher in 2009–2011 (adjusted odds ratio 5.07 (95% CI 3.12–8.24), p < 0.001), but remained unchanged in subsequent periods. Male sex and low CD4 T-cell count independently increased odds for KS.ConclusionsDespite ART expansion, KS at enrollment showed no significant decline. The low CD4 cell count, across all periods, indicates delay in enrollment for HIV care, which increases KS risk. Interventions aimed at early HIV diagnosis and linkage to ART is critical to KS risk reduction in this population.

Motivational interviewing retention counseling and adherence to early infant diagnostic HIV testing schedule in South Africa: The PAEDLINK randomized trial.

Introduction:We report the PAEDLINK randomized trial results on the effect of motivational interviewing (MI) retention counseling on the adherence of postpartum women to the early infant diagnostic human immunodeficiency virus (HIV) testing schedule.Methods:HIV positive women and their babies were enrolled 3 to 6 days after delivery at 4 midwife obstetric units in the Gauteng province of South Africa and randomized into (A) MI retention counseling and telephonic tracing, (B) biannual telephonic tracing, and (C) standard care. Mother–baby pairs were followed up for 18 months via medical records. The uptake of child HIV tests and maternal retention in the 0 to 6 and 7 to 18 month periods were modeled using Log-binomial regression.Results:Overall, 501/711 enrolled mother–baby pairs received a second HIV polymerase chain reaction test by 6 months (70.0%, 70.5%, and 70.0% in groups A, B, and C, respectively). A higher proportion of intervention children (60.9%) were tested at 7 to 90 days than group B (48.1%, adjusted risk ratio [aRR] 0.8 for B vs A, 95% confidence interval [CI]: 0.7–0.9) and group C children (52.7%, aRR 0.9 for C vs A, 95% CI: 0.9–1.0). Child testing between 7 and 18-months was also higher in group A than C (10.7% A, vs 5.5% C, RR 2.0, 95% CI: 1.0–3.7). However, maternal retention was similar across groups, with 41.6% and 16.3% retained during the 0 to 6 and the 7 to 18-months periods, respectively.Conclusion:MI retention counseling can reduce delays in the early infant diagnosis testing schedule for HIV-exposed infants. However, further support is necessary to maximize later HIV tests and maternal retention.

Factors associated with viral suppression among cisgender women living with human immunodeficiency virus in the United States: An integrative review.

Introduction:Women account for 23% of new human immunodeficiency virus diagnoses in the United States, yet remain understudied. Adherence to antiretroviral therapy and consequent viral suppression are keys to preventing human immunodeficiency virus transmission, reducing risk of drug resistance, and improving health outcomes.Objectives:This review identified and synthesized peer-reviewed studies in the United States describing factors associated with viral suppression among cisgender women living with human immunodeficiency virus.Methods:We searched five databases: Cumulative Index to Nursing and Allied Health (CINAHL), PubMed, Embase, Scopus, and PsycINFO, and reported the findings using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Eligible studies included: (1) peer-reviewed English-language articles published since 2010; (2) includes only cisgender women; (3) participants were at least 18 years of age; (4) reported metrics on viral loads; and (5) conducted in the United States.Results:Fourteen studies in total were reviewed. Eight studies had adult women living with human immunodeficiency virus, four recruited only pregnant women, and two included only racial minority women. The most commonly reported factors negatively associated with viral suppression were substance use (n = 4), followed by availability of health insurance, financial constraint, complexity of human immunodeficiency virus treatment regimen (n = 3), and intimate partner violence (n = 2). Other factors were depression, race, and age. In addition, all four studies that included only pregnant women reported early human immunodeficiency virus care engagement as a significant predictor of low viral loads pre- and post-partum.Conclusion:Substance use, financial constraint, lack of health insurance, human immunodeficiency virus treatment regimen type, intimate partner violence, and late human immunodeficiency virus care pre–post pregnancy were the most common factors negatively associated with viral suppression. There is a paucity of data on viral suppression factors related to transgender and rural populations. More human immunodeficiency virus research is needed to explore factors associated with human immunodeficiency virus treatment outcomes in transgender women and cisgender women in rural U.S. regions.

A Randomized Trial of Point-of-Care Early Infant Human Immunodeficiency Virus (HIV) Diagnosis in Zambia.

BackgroundPoint-of-care (POC) early infant diagnosis (EID) provides same-day results and the potential for immediate initiation of antiretroviral therapy (ART).MethodsWe conducted a pragmatic trial at 6 public clinics in Zambia. HIV-exposed infants were individually randomized to either (1) POC EID (onsite testing with the Alere q HIV-1/2 Detect) or (2) enhanced standard of care (SOC) EID (off-site testing at a public laboratory). Infants with HIV were referred for ART and followed for 12 months. Our primary outcome was defined as alive, in care, and virally suppressed at 12 months.ResultsBetween March 2016 and November 2018, we randomized 4000 HIV-exposed infants to POC (n=1989) or SOC (n=2011). All but 2 infants in the POC group received same-day results, while the median time to result in the SOC group was 27 (interquartile range: 22–30) days. Eighty-one (2%; 95% confidence interval [CI]: 1.6–2.5%) infants were diagnosed with HIV. Although ART initiation was high, there were 15 (19%) deaths, 15 (19%) follow-up losses, and 31 (38%) virologic failures. By 12 months, only 20 of 81 (25%; 95% CI: 15–34%) infants with HIV were alive, in care, and virally suppressed: 13 (30%; 16–43%) infants in the POC group vs 7 (19%; 6–32%) in the SOC group (RR: 1.56; .7–3.50).ConclusionsPOC EID eliminated diagnostic delays and accelerated ART initiation but did not translate into definitive improvement in 12-month outcomes. In settings where centralized EID is well functioning, POC EID is unlikely to improve pediatric HIV outcomes.Clinical Trials RegistrationThis trial is registered at https://clinicaltrials.gov (NCT02682810).

Evaluation of serological assays for the diagnosis of HIV infection in adults.

Serological tests based on the enzyme immunoassay (EIA) are the primary tool for the diagnosis of human immunodeficiency virus (HIV) in adults and have rapidly evolved to quicker, affordable and more accurate test formats to detect early HIV infection. Second- and third-generation HIV rapid tests detect the immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to the HIV and are used at the point of care and in HIV self-testing. The tests are affordable and accessible in state and private diagnostic laboratories. The present-day fourth- and fifth-generation EIAs can detect both p24 antigen and IgG and IgM HIV antibodies and thereby diagnose early HIV infection at approximately 2 weeks. The fourth- and fifth-generation EIAs also report sensitivity and specificity of more than 99%. The correct interpretation of HIV diagnosis of false-positive and false-negative EIA test results requires collaborative scrutiny of patient factors and laboratory test methodologies.

Alterations in the oral microbiome in HIV infection: causes, effects and potential interventions.

A massive depletion of CD4+ T lymphocytes has been described in early and acute human immunodeficiency virus (HIV) infection, leading to an imbalance between the human microbiome and immune responses. In recent years, a growing interest in the alterations in gut microbiota in HIV infection has led to many studies; however, only few studies have been conducted to explore the importance of oral microbiome in HIV-infected individuals. Evidence has indicated the dysbiosis of oral microbiota in people living with HIV (PLWH). Potential mechanisms might be related to the immunodeficiency in the oral cavity of HIV-infected individuals, including changes in secretory components such as reduced levels of enzymes and proteins in saliva and altered cellular components involved in the reduction and dysfunction of innate and adaptive immune cells. As a result, disrupted oral immunity in HIV-infected individuals leads to an imbalance between the oral microbiome and local immune responses, which may contribute to the development of HIV-related diseases and HIV-associated non-acquired immunodeficiency syndrome comorbidities. Although the introduction of antiretroviral therapy (ART) has led to a significant decrease in occurrence of the opportunistic oral infections in HIV-infected individuals, the dysbiosis in oral microbiome persists. Furthermore, several studies with the aim to investigate the ability of probiotics to regulate the dysbiosis of oral microbiota in HIV-infected individuals are ongoing. However, the effects of ART and probiotics on oral microbiome in HIV-infected individuals remain unclear. In this article, we review the composition of the oral microbiome in healthy and HIV-infected individuals and the possible effect of oral microbiome on HIV-associated oral diseases. We also discuss how ART and probiotics influence the oral microbiome in HIV infection. We believe that a deeper understanding of composition and function of the oral microbiome is critical for the development of effective preventive and therapeutic strategies for HIV infection.

Effects of nutritional supplementation on glucose metabolism and insulin function among people with HIV initiating ART

BackgroundWithout high-quality nutritional support, there is a risk that people infected with human immunodeficiency virus (HIV) will replace lost muscle mass with fat mass when initiating antiretroviral therapy (ART). We have shown that lipid-based nutrient supplements (LNS) with whey or soy considerably increases lean mass among Ethiopian people with HIV starting ART. Here, we aim to assess the effects of LNS on insulin function and glucose metabolism.MethodsThis is a secondary analysis of a randomized trial testing the effect of three-month supplementation with LNS containing whey (LNS/whey) or soy (LNS/soy) among people with HIV. LNS/whey and LNS/soy groups were combined and then were compared against the non-supplemented group. The outcomes were change in fasting plasma-glucose (FPG), and 30-min glucose and 120-min glucose after oral glucose tolerance test. We further assessed effect on glycated hemoglobin (HbA1c), fasting insulin, homeostatic model assessment index for beta-cell function (HOMA-B) and insulin resistance (HOMA-IR).ResultsOf the 318 patients enrolled, 268 (84.3%) had available FPG and HbA1c and included. After 3 months of ART, HbA1c tended to be 2 mmol/mol higher in the LNS supplemented group, most pronounced among those receiving whey as the protein source. LNS led to higher 30-min glucose (0.5 mmol/L, 95% CI 0.2, 0.8) and 120-min glucose (0.4 mmol/L, 95% CI 0.03, 0.8) and a > 50% increase in fasting insulin, HOMA-B and HOMA-IR compared to the non-supplemented.ConclusionAmong Ethiopian people with HIV initiating ART, short-term LNS intake increased glucose and insulin levels, and tended to increase HbA1c, potentially leading to more insulin resistance. Higher intake of carbohydrates with LNS could influence glycemic status. Whether these metabolic changes in early HIV treatment are beneficial or increase long-term risk of metabolic disorders needs to be explored.

Landscape of T Cells Transcriptional and Metabolic Modules During HIV Infection Based on Weighted Gene Co-expression Network Analysis.

Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS). HIV infection affects the functions and metabolism of T cells, which may determine the fate of patients; however, the specific pathways activated in different T-cell subtypes (CD4+ and CD8+ T cells) at different stages of infection remain unclear. We obtained transcriptome data of five individuals each with early HIV infection, chronic progressive HIV infection, and no HIV infection. Weighted gene co-expression network analysis was used to evaluate changes in gene expression to determine the antiviral response. An advanced metabolic algorithm was then applied to compare the alterations in metabolic pathways in the two T-cell subtypes at different infection stages. We identified 23 and 20 co-expressed gene modules in CD4+ T and CD8+ T cells, respectively. CD4+ T cells from individuals in the early HIV infection stage were enriched in genes involved in metabolic and infection-related pathways, whereas CD8+ T cells were enriched in genes involved in cell cycle and DNA replication. Three key modules were identified in the network common to the two cell types: NLRP1 modules, RIPK1 modules, and RIPK2 modules. The specific role of NLRP1 in the regulation of HIV infection in the human body remains to be determined. Metabolic functional analysis of the two cells showed that the significantly altered metabolic pathways after HIV infection were valine, leucine, and isoleucine degradation; beta-alanine metabolism; and PPAR signaling pathways. In summary, we found the core gene expression modules and different pathways activated in CD4+ and CD8+ T cells, along with changes in their metabolic pathways during HIV infection progression. These findings can provide an overall resource for establishing biomarkers to facilitate early diagnosis and potential guidance for new targeted therapeutic strategies.