Acute HIV Infection Research Articles

Getting acute HIV infection under control

Department of Internal Medicine, OLVG, Amsterdam, The Netherlands. Correspondence to Kees Brinkman, MD, PhD, Department of Internal Medicine, OLVG, Oosterpark 9, 1091AC Amsterdam, The Netherlands. E-mail: [email protected] Received 6 February, 2023 Accepted 8 February, 2023

Cultural and religious barriers in the Middle East leading to delayed management of acute HIV case resulting in irreversible blindness: a case report.

A 26-year-old male who resides in a country in the Middle East visited the local general hospital emergency department on 17 July 2018. He presented with symptoms of persistent upper respiratory tract infection, dysphagia, and generalized fatigue. Denied any previous history of sexual contact, smoking, drinking, or using illicit drugs. This patient repeatedly attended the emergency department seeking medical attention and was treated for viral and bacterial upper respiratory tract symptoms by conservative and antibiotic therapy, yielded in short term relief but recurrence and worsening symptoms, especially dysphagia symptoms. On examination, the patient looked unwell, cachectic, and frail with normal vital signs and no positive findings on chest and abdominal examination; however, Ear Nose and Throat and oral examination revealed extensive oropharyngeal candidiasis. That is when he was suspected of having an immunodeficiency syndrome of some sort, and based on those serious findings, he was advised hospital admission for further investigations, diagnosis and management. The patient refused hospital admission against medical advice despite all the potential risks explained clearly, as he had a pre-planned family reunion holiday to Turkey, which was again strongly advised against as likely he will deteriorate while on holiday, but he went on with his plan, accordingly, oropharyngeal candidiasis was successfully treated with oral antifungal tablets, pending further investigations and definitive management. Then in 24 July 2018, he travelled to Turkey, where he developed symptoms of shortness of breath and dry a cough then he became systemically unwell and was admitted to a local hospital in Turkey where he was diagnosed with a lower respiratory tract infection and treated with intravenous antibiotics for 7 days; then on 6 August 2018, he flew back on an emergency flight to his home country, where he was admitted to the acute medical admission unit and arranged to have patient laboratory investigations. The results revealed positive HIV infection with a plasma HIV viral load was greater than 3000000 copies/ml, and advanced immunosuppression with CD3+/CD4+ T-lymphocyte was 40 cells/mm3. The social aspect of this case was apparent from denying sexual contact. The patient did not have any history of surgical operations, no family history of HIV infection, no previous blood transfusion, or use of contaminated syringes. By exclusion sexual mode of transmission is the only possible way of contracting HIV infection in this case, considering the fact that he was outside his country as single man for few years while studying. In the Middle East countries, due to religious and cultural reservations coupled with HIV diagnosis stigma, the diagnosis of the serious sexually transmitted infections such as HIV is usually delayed, as a result these patients will go on and develop late-stage disease and irreversible complications when diagnosed, entering the AIDS stage with rapid progression of irreversible complications like Cytomegalovirus, Ear Nose and Throat retinitis and blindness before they start definitive treatment. The oropharyngeal candidiasis and repeated upper and lower respiratory tract infections that are non-responding to therapy are usually red flag signs of immunosuppression, which warrants high clinical vigilance from the clinician side to take a detailed sexual history and rule out acute HIV infection by testing for it at early stages, in patients with high clinical suspicion , in addition to the other possible causes of immunosuppression. Therefore, assuring confidentiality, taking a careful sexual history and gathering data in an acceptable way for these patients and considering a holistic approach yield a better management outcome.

Patient-reported outcomes among virally suppressed people living with HIV after switching to Co-formulated bictegravir, emtricitabine and tenofovir alafenamide.

While some evidence has suggested the benefits of co-formulated bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) in improving the quality of life of people living with HIV (PLWH), patient-reported outcome studies that focus on Asian population remain scarce. We aimed to determine the changes in HIV-related symptom burden in virally-suppressed PLWH switching to B/F/TAF in a real-world setting. PLWH on stable antiretroviral therapy (ART) for ≥6 months with plasma HIV RNA <200 copies/mL who decided to switch to B/F/TAF were eligible for the study. Participants' experience with 20 symptoms were assessed using HIV Symptom Index at baseline and weeks 24 and 48. Responses were dichotomized in two ways: 1) present vs. not present; and 2) bothersome vs. not bothersome, and compared across time points. Six hundred and thirty participants (prior regimen, 94.4% integrase inhibitor-based) who completed week 48 visit were included in the analysis. Forty-eight weeks after switching to B/F/TAF, six symptoms were significantly less prevalent, and seven symptoms were significantly less bothersome. Improvement was more pronounced in participants whose prior regimen was elvitegravir-based versus dolutegravir-based. Logistic regression results showed that prior dolutegravir-based ART and pre-existing diabetes independently predicted improvement in diarrhea/loose bowels and muscle aches/joint pain, respectively. Despite the overall improvement, some symptoms persisted in a substantial proportion of participants. Virally-suppressed PLWH might benefit from a regimen switch to B/F/TAF to reduce the prevalence and level of bother of HIV-related symptoms. Nevertheless, additional multidisciplinary interventions are warranted to further alleviate the symptom burden of PLWH.

Efficacy and Safety of Two-Drug Regimens That Are Approved from 2018 to 2022 for the Treatment of Human Immunodeficiency Virus (HIV) Disease and Its Opportunistic Infections.

The human immunodeficiency virus (HIV) is a type of virus that targets the body's immune cells. HIV infection can be divided into three phases: acute HIV infection, chronic HIV infection, and acquired immunodeficiency syndrome (AIDS). HIV-infected people are immunosuppressed and at risk of developing opportunistic infections such as pneumonia, tuberculosis, candidiasis, toxoplasmosis, and Salmonella infection. The two types of HIV are known as HIV-1 and HIV-2. HIV-1 is the predominant and more common cause of AIDS worldwide, with an estimated 38 million people living with HIV-1 while an estimated 1 to 2 million people live with HIV-2. No effective cures are currently available for HIV infection. Current treatments emphasise the drug's safety and tolerability, as lifelong management is needed to manage HIV infection. The goal of this review is to study the efficacy and safety of newly approved drugs from 2018 to 2022 for the treatment of HIV by the United States Food and Drug Administration (US-FDA). The drugs included Cabotegravir and Rilpivirine, Fostemsavir, Doravirine, and Ibalizumab. From the review, switching to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) was shown to be noninferior to the continuation of the previous regimen, efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) in virologically suppressed adults with HIV-1. However, DOR/3TC/TDF had shown a preferable safety profile with lower discontinuations due to adverse events (AEs), lower neuropsychiatric AEs, and a preferable lipid profile. Ibalizumab was also safe, well tolerated, and had been proven effective against multiple drug-resistant strains of viruses.

Depression, Alcohol Use, and Sexual Behaviors by HIV Infection Stage and Diagnosis Timing Among STI Clinic Patients in Lilongwe, Malawi.

Understanding depression, alcohol use, and sexual behaviors according to HIV infection stage and diagnosis timing is important for HIV prevention efforts. We enrolled persons with recent infection and diagnosis (i.e., acute HIV infection (AHI) (n = 92) persons newly diagnosed seropositive (n = 360)) and persons previously diagnosed with HIV (n = 190) into a randomized controlled trial in Lilongwe, Malawi (N = 641) and estimated the prevalence of probable depression (Patient Health Questionnaire-9 ≥ 5), hazardous alcohol use (Alcohol Use Disorder Identification Test-C: men ≥ 4; women ≥ 3), and sexual behaviors (transactional sex, condomless sex). Compared with previously diagnosed participants, participants newly seropositive and those with AHI reported a higher proportion of probable depression (7%, 27%, 38%; AHI/Previous: Table Probability: 0.02, p < 0.01; AHI/New: Table Probability: <0.01, p < 0.01), hazardous alcohol use (8%, 18%, 29%; AHI/Previous and AHI/New: Table Probability: <0.01, p < 0.01), and transactional sex (5%, 14%, 20%; AHI/Previous: Table Probability: <0.01, p < 0.01; AHI/New: Table Probability: 0.06, p = 0.24), respectively. HIV prevention services addressing mental health and alcohol misuse may be particularly beneficial for persons with recent HIV infection and or diagnosis.

Per-pathogen virulence of HIV-1 subtypes A, C and D.

HIV-1 subtypes differ in their clinical manifestations and the speed in which they spread. In particular, the frequency of subtype C is increasing relative to subtypes A and D. We investigate whether HIV-1 subtypes A, C and D differ in their per-pathogen virulence and to what extend this explains the difference in spread between these subtypes. We use data from the hormonal contraception and HIV-1 genital shedding and disease progression among women with primary HIV infection study. For each study participant, we determine the set-point viral load value, CD4+ T cell level after primary infection and CD4+ T cell decline. Based on both the CD4+ T cell count after primary infection and CD4+ T cell decline, we estimate the time until AIDS. We then obtain our newly introduced measure of virulence as the inverse of the estimated time until AIDS. After fitting a model to the measured virulence and set-point viral load values, we tested if this relation varies per subtype. We found that subtype C has a significantly higher per-pathogen virulence than subtype A. Based on an evolutionary model, we then hypothesize that differences in the primary length of infection period cause the observed variation in the speed of spread of the subtypes.

What explains the poor contraction of the viral load during paediatric HIV infection?

An acute HIV infection in young children differs markedly from that in adults: Children have higher viral loads (VL), and a poor contraction to a setpoint VL that is not much lower than the peak VL. As a result, children progress faster towards AIDS in the absence of treatment. We used a classical ordinary differential equation model for viral infection dynamics to study why children have a lower viral contraction ratio than adults. We performed parameter sweeps to identify factors explaining the observed difference between children and adults. We grouped parameters associated with the host, the infection, or the immune response. Based on paediatric data available from datasets within the EPIICAL project (https://www.epiical.org/), we refuted that viral replication rates differ between young children and adults, and therefore these cannot be responsible for the low VL contraction ratios seen in children. The major differences in lowering VL contraction ratio resulted from sweeping the parameters linked to the immune response. Thus, we postulate that an ”ineffective” (late and/or weak) immune response is the most parsimonious explanation for the higher setpoint VL in young children, and hence the reason for their fast disease progression.

Genomic Evidence for the Nonpathogenic State in HIV-1-Infected Northern Pig-Tailed Macaques.

HIV-1 is a highly host-specific retrovirus that infects humans but not most nonhuman primates. Thus, the lack of a suitable primate model that can be directly infected with HIV-1 hinders HIV-1/AIDS research. In the previous study, we have found that the northern pig-tailed macaques (NPMs) are susceptible to HIV-1 infection but show a nonpathogenic state. In this study, to understand this macaque-HIV-1 interaction, we assembled a de novo genome and longitudinal transcriptome for this species during the course of HIV-1 infection. Using comparative genomic analysis, a positively selected gene, Toll-like receptor 8, was identified with a weak ability to induce an inflammatory response in this macaque. In addition, an interferon-stimulated gene, interferon alpha inducible protein 27, was upregulated in acute HIV-1 infection and acquired an enhanced ability to inhibit HIV-1 replication compared with its human ortholog. These findings coincide with the observation of persistently downregulated immune activation and low viral replication and can partially explain the AIDS-free state in this macaque following HIV-1 infection. This study identified a number of unexplored host genes that may hamper HIV-1 replication and pathogenicity in NPMs and provided new insights into the host defense mechanisms in cross-species infection of HIV-1. This work will facilitate the adoption of NPM as a feasible animal model for HIV-1/AIDS research.

Cohort profile: a longitudinal study of HIV infection in the central nervous system with focus on cerebrospinal fluid – the Gothenburg HIV CSF Study Cohort

PurposeIn order to enable long-term follow-up of the natural course of HIV infection in the central nervous system, a longitudinal cohort study with repeated cerebrospinal fluid (CSF) analyses at intervals...

Iterative hypothesis testing in HIV vaccine research: moving towards success.

Iterative hypothesis testing in HIV vaccine research: moving towards success.

Effect of Human Immunodeficiency Virus Infection on the Incidence and Severity of Neurological Post-Acute Sequelae of COVID-19 (S21.009)

<h3>Objective:</h3> To investigate whether HIV infection is an independent prognostic factor of neurological post-acute sequelae of COVID-19 (PASC). <h3>Background:</h3> HIV has been linked to an increase in severity of symptoms of PASC. <h3>Design/Methods:</h3> COVID-19 inpatients from a tertiary care center were collected and retrospectively studied for presence of neurological PASC symptoms, 4 weeks to up to 1 year after their first inpatient admission COVID-19. Patients with HIV and COVID-19 were compared to non-HIV COVID-19 patients. All demographic, nominal and inpatient data including length of stay, discharge, medications and lab data was compared. The proportion of patients reporting neurological PASC symptoms in HIV vs non-HIV patients with a history of COVID-19 were compared. <h3>Results:</h3> 277 patients who had an outpatient follow-up or were readmitted to the hospital were reviewed. 27 patients had HIV and 22 followed up. There was no significant difference in age between HIV and non-HIV groups (55.3±11.3 vs 52.5±18.5 p&gt;0.05) For HIV vs non-HIV patients with a history of COVID-19, numbness (18.2% vs 10.5%) paresthesias (9.1% vs 7.5%), brain fog or cognitive impairment (9.1% vs 6.7%), weakness (18.1% vs 27.1%), fatigue (31.2% vs 30.6%), headaches (18.1% vs 16.9%), changes in smell of taste (18.1% or 11.7), sleep issues or insomnia (13.6% vs 9.4%) and anxiety or depression (27.7% vs 18.0%) were reported between 4 weeks and 1 year after admission. Although there is an increased incidence of most neurological PASC symptoms in HIV compared to non-HIV, the difference did not reach significance. <h3>Conclusions:</h3> This preliminary analysis of COVID-19 patients with 1 year follow-up demonstrates that the incidence of neurological symptoms of PASC in HIV patients vs non-HIV patients did not significantly differ. The incidence reported in this study agrees with prior literature on the incidence of neurological PASC. Work is in progress expand the study size and control for concomitant neurological conditions. <b>Disclosure:</b> Mr. Jaffry has nothing to disclose. Mr. Mandava has nothing to disclose. Mr. Jaffry has nothing to disclose. Mr. Ors has nothing to disclose. Miss Shaikh has nothing to disclose. Mr. Trivedi has nothing to disclose. Ms. Faiz has nothing to disclose. Mr. Gerges has nothing to disclose. Prof. Boufadel has nothing to disclose. Dr. Souayah has received publishing royalties from a publication relating to health care.

Persistent T cell proliferation and MDSCs expansion precede incomplete CD4+ T cell recovery in people with acute HIV-1 infection with early ART

HIV-1 infection causes T cell dysfunction that cannot be fully restored by anti-retroviral therapy (ART). Myeloid-derived suppressor cells (MDSCs) expand and suppress T cell function during viral infection. In this study, we evaluated the dynamics of phenotypes and function of T cells and MDSCs and the effects of their interaction on CD4+ T cell reconstitution in people with acute HIV-1 infection (PWAH) with early ART. Flow cytometry was used to detect the phenotypic dynamics and function of T cells and MDSCs at pre-ART, 4, 24, 48, and 96 weeks of ART. We observed that T cells were hyper-activated and hyper-proliferative in PWAH at pre-ART. Early ART normalized T cell activation but not their proliferation. T cell proliferation, enriched in PD-1+ T cells, was persisted and negatively associated with CD4+ T-cell counts after ART. Moreover, M-MDSCs frequency was increased and positively correlated with T cell proliferation after 96 weeks of ART. M-MDSCs persisted and inhibited T cell proliferation ex vivo, which could be partially reversed by PD-L1 blockade. Further, we found higher frequencies of proliferative CD4+ T cells and M-MDSCs in PWAH with lower CD4+ T cell numbers (<500 cells/μL) compared to PWAH with higher CD4+ T cell numbers (>600 cells/μL) after 96 weeks of ART. Our findings indicate that persistent T cell proliferation, MDSCs expansion, and their interaction may affect CD4+ T-cell recovery in PWAH with early ART.

Transforming Growth Factor β Signaling Promotes HIV-1 Infection in Activated and Resting Memory CD4+ T Cells.

Understanding the facilitator of HIV-1 infection and subsequent latency establishment may aid the discovery of potential therapeutic targets. Here, we report the elevation of plasma transforming growth factor β (TGF-β) during acute HIV-1 infection among men who have sex with men (MSM). Using a serum-free in vitro system, we further delineated the role of TGF-β signaling in mediating HIV-1 infection of activated and resting memory CD4+ T cells. TGF-β could upregulate both the frequency and expression of the HIV-1 coreceptor CCR5, thereby augmenting CCR5-tropic viral infection of resting and activated memory CD4+ T cells via Smad3 activation. The production of live HIV-1JR-FL upon infection and reactivation was increased in TGF-β-treated resting memory CD4+ T cells without increasing CD4 expression or inducing T cell activation. The expression of CCR7, a central memory T cell marker that serves as a chemokine receptor to facilitate T cell trafficking into lymphoid organs, was also elevated on TGF-β-treated resting and activated memory CD4+ T cells. Moreover, the expression of CXCR3, a chemokine receptor recently reported to facilitate CCR5-tropic HIV-1 infection, was increased on resting and activated memory CD4+ T cells upon TGF-β treatment. These findings were coherent with the observation that ex vivo CCR5 and CXCR3 expression on total resting and resting memory CD4+ T cells in combination antiretroviral therapy (cART)-naive and cART-treated patients were higher than in healthy individuals. Overall, the study demonstrated that TGF-β upregulation induced by acute HIV-1 infection might promote latency reservoir establishment by increasing infected resting memory CD4+ T cells and lymphoid organ homing of infected central memory CD4+ T cells. Therefore, TGF-β blockade may serve as a potential supplementary regimen for HIV-1 functional cure by reducing viral latency. IMPORTANCE Incomplete eradication of HIV-1 latency reservoirs remains the major hurdle in achieving a complete HIV/AIDS cure. Dissecting the facilitator of latency reservoir establishment may aid the discovery of druggable targets for HIV-1 cure. This study showed that the T cell immunomodulatory cytokine TGF-β was upregulated during the acute phase of infection. Using an in vitro serum-free system, we specifically delineated that TGF-β promoted HIV-1 infection of both resting and activated memory CD4+ T cells via the induction of host CCR5 coreceptor. Moreover, TGF-β-upregulated CCR7 or CXCR3 might promote HIV-1 latent infection by facilitating lymphoid homing or IP-10-mediated viral entry and DNA integration, respectively. Infected resting and central memory CD4+ T cells are important latency reservoirs. Increased infection of these cells mediated by TGF-β will promote latency reservoir establishment during early infection. This study, therefore, highlighted the potential use of TGF-β blockade as a supplementary regimen with cART in acute patients to reduce viral latency.

IL-15 enhances HIV-1 infection by promoting survival and proliferation of CCR5+CD4+ T cells.

HIV-1 usually utilizes CCR5 as its coreceptor and rarely switches to a CXCR4-tropic virus until the late stage of infection. CCR5+CD4+ T cells are the major virus-producing cells in viremic individuals as well as SIV-infected nonhuman primates. The differentiation of CCR5+CD4+ T cells is associated with the availability of IL-15, which increases during acute HIV-1 infection. Here, we report that CCR5 was expressed by CD4+ T cells exhibiting effector or effector memory phenotypes with high expression levels of the IL-2/IL-15 receptor common β and γ chains. IL-15, but not IL-7, improved the survival of CCR5+CD4+ T cells, drove their expansion, and facilitated HIV-1 infection in vitro and in humanized mice. Our study suggests that IL-15 plays confounding roles in HIV-1 infection, and future studies on the IL-15-based boosting of anti-HIV-1 immunity should carefully examine the potential effects on the expansion of HIV-1 reservoirs in CCR5+CD4+ T cells.

Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses

The genetic diversity of HIV impedes vaccine development. Identifying the viral properties of transmitted/founder (T/F) variants may provide a common vaccine target. To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. Eighteen full-length T/F clones were generated from 9 women and six chronic infection clones were from 2 individuals. All clones but one were non-recombinant subtype C. Three of the 5 T/F clones and 3 chronic clones tested replicated efficiently in PBMCs and utilised CCR5 coreceptor for cell entry. Transmitted/founder and chronic infection clones displayed heterogenous in vitro replicative capacity and resistance to type I interferon. T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. Our findings suggest MTF transmission may select viruses with compact envelopes.

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.

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.

Evaluation of serum calcitonin gene related peptide (CGRP) Level in HIV infected patients as an indicator of disease activity

Human immunodeficiency virus (HIV) infection is under global attention due to its rapid spread and high rate of morbidity and mortality. HIV gets an access into the mucosa of genital epithelium through binding to Langerhans cells. While viral load and CD4+ cell count are the main parameters to detect disease activity, new biomarkers are introduced as a potential parameter for monitoring of disease activity in HIV infected patients. Calcitonin Gene Related Peptide (CGRP) is a neuropeptide that is secreted by peripheral neurons at genital epithelia and plays an important role in limitation of HIV transmission and spread to infected CD4+ cells through its effect onto Langerhans cells. This study aimed to evaluate the serum level of CGRP in HIV infected patients and to determine whether CGRP can serve as an indicator of HIV infection activity. The study included 104 HIV patients and 24 normal controls. Patients were divided into four groups. Serum levels of CGRP were measured by ELISA and correlated to viral load and CD4+ cells count for patients in the four groups: primary HIV infection (PHI), chronic HIV infection (CHI) before combinational antiretroviral therapy (cART-naïve), chronic HIV infection after one year of cART-initiation, and chronic HIV infection after two years of cART. Serum levels of CGRP were also measured in sera of controls and compared to patients' groups. Serum levels of CGRP were significantly lower in cART naïve PHI and CHI patients in comparison with normal controls (p < 0.05), Also, serum CGRP levels were positively correlated with CD4+ cells count (p < 0.01), but negatively correlated with viral load (p>0.05). In conclusion, CGRP could be proposed as an indicator of disease activity in HIV patients.

Molecular immunological techniques to support the differential microbiological diagnosis of acute HIV infection

This research sought to identify HIV confirmatory molecular immunological methods for the early diagnosis of acute infections, complementing the differential microbiological diagnosis. A descriptive study of a clinical case was carried out using molecular immunological analyses. The results showed that molecular immunological methods range from third generation techniques, capable of diagnosing the infection in the acute phase, to fourth generation techniques that detect the infection from the third week of infection. Confirmatory tests, such as Western Blot and LIA, presented high sensitivity and specificity. Revised molecular techniques, such as p24 detection or Polymerase Chain Reaction (PCR), reduced diagnosis time. In conclusion, molecular immunological methods allow early detection of HIV with high precision, providing diagnostic and confirmation results from the third week of infection.

The End Is in Sight: Current Strategies for the Elimination of HIV Vertical Transmission.

The goal of this review is to highlight and interpret recent trends and developments in the diagnosis, treatment, and prevention of HIV vertical transmission from a clinical perspective. Universal third-trimester retesting and partner testing may better identify incident HIV among pregnant patients and result in early initiation of antiretroviral therapy to prevent vertical transmission. The proven safety and efficacy of integrase inhibitors such as dolutegravir may be particularly useful in suppressing viremia in pregnant persons who present late for ART treatment. Pre-exposure prophylaxis (PrEP) during pregnancy may play a role in preventing HIV acquisition; however, its role in preventing vertical transmission is difficult to elucidate. Substantial progress has been made in recent years to eliminate HIV perinatal transmission. Future research hinges upon a multipronged approach to improving HIV detection, risk-stratified treatment strategies, and prevention of primary HIV infection among pregnant persons.