Integrating health services for HIV infection, diabetes and hypertension in sub-Saharan Africa: a cohort study

BackgroundHIV, diabetes and hypertension have a high disease burden in sub-Saharan Africa. Healthcare is organised in separate clinics, which may be inefficient. In a cohort study, we evaluated integrated management of these conditions from a single chronic care clinic.ObjectivesTo determined the feasibility and acceptability of integrated management of chronic conditions in terms of retention in care and clinical indicators.Design and settingProspective cohort study comprising patients attending 10 health facilities offering primary care in Dar es Salaam and Kampala.InterventionClinics within health facilities were set up to provide integrated care. Patients with either HIV, diabetes or hypertension had the same waiting areas, the same pharmacy, were seen by the same clinical staff, had similar provision of adherence counselling and tracking if they failed to attend appointments.Primary outcome measuresRetention in care, plasma viral load.FindingsBetween 5 August 2018 and 21 May 2019, 2640 patients were screened of whom 2273 (86%) were enrolled into integrated care (832 with HIV infection, 313 with diabetes, 546 with hypertension and 582 with multiple conditions). They were followed up to 30 January 2020. Overall, 1615 (71.1%)/2273 were female and 1689 (74.5%)/2266 had been in care for 6 months or more. The proportions of people retained in care were 686/832 (82.5%, 95% CI: 79.9% to 85.1%) among those with HIV infection, 266/313 (85.0%, 95% CI: 81.1% to 89.0%) among those with diabetes, 430/546 (78.8%, 95% CI: 75.4% to 82.3%) among those with hypertension and 529/582 (90.9%, 95% CI: 88.6 to 93.3) among those with multimorbidity. Among those with HIV infection, the proportion with plasma viral load <100 copies/mL was 423(88.5%)/478.ConclusionIntegrated management of chronic diseases is a feasible strategy for the control of HIV, diabetes and hypertension in Africa and needs evaluation in a comparative study.

Modeling HIV-1 Within-Host Dynamics After Passive Infusion of the Broadly Neutralizing Antibody VRC01

VRC01 is a broadly neutralizing antibody that targets the CD4 binding site of HIV-1 gp120. Passive administration of VRC01 in humans has assessed the safety and the effect on plasma viremia of this monoclonal antibody (mAb) in a phase 1 clinical trial. After VRC01 infusion, the plasma viral load in most of the participants was reduced but had particular dynamics not observed during antiretroviral therapy. In this paper, we introduce different mathematical models to explain the observed dynamics and fit them to the plasma viral load data. Based on the fitting results we argue that a model containing reversible Ab binding to virions and clearance of virus-VRC01 complexes by a two-step process that includes (1) saturable capture followed by (2) internalization/degradation by phagocytes, best explains the data. This model predicts that VRC01 may enhance the clearance of Ab-virus complexes, explaining the initial viral decay observed immediately after antibody infusion in some participants. Because Ab-virus complexes are assumed to be unable to infect cells, i.e., contain neutralized virus, the model predicts a longer-term viral decay consistent with that observed in the VRC01 treated participants. By assuming a homogeneous viral population sensitive to VRC01, the model provides good fits to all of the participant data. However, the fits are improved by assuming that there were two populations of virus, one more susceptible to antibody-mediated neutralization than the other.

HLA Class I and Plasma Viral Load of HIV-1 in Sexually Transmitted and Reproductive Tract Infections among Heterosexual Serodiscordant couples in Nigeria

ABSTRACTBackgroundThis study investigated HLA Class I in Long Term Non-progressors (LTNPs) and plasma viral load in Sexually Transmitted and Reproductive Tract Infections (STIs/RTIs) associated with Heterosexual HIV-1 transmission among serodiscordant couples in Nigeria.MethodsA total of 271 serodiscordant and concordant couples (HIV positive and negative) were enrolled, blood samples were collected from the subjects by venipuncture. HLA class I (with specific primers), plasma viral load, CD4+ analysis was done. Endocervical/urethral swabs and early morning urine samples were collected by standard microbiological methods. These were screened by microscopy, culture, antibiogram, and biochemical tests with a view to identify aetiologic agents of co-infections with HIV.ResultsThe Participants age ranged from ≥ 21- < 50years. The index whose plasma viral loads were 10,001-100,000 copies/ml had STIs/RTIs 32(60.9% p=0.059). Staphylococcus aureus and Escherichia coli (22.1%) were isolated from the index (HIV positive subject) while 14.5% of Staphylococcus aureus and 27.2% of E coli were isolated from their partners (HIV negative subject). Staphylococcus aureus and E coli are normal flora but because the patients are Immunocompromised as a result of positivity to HIV, Staphylococcus aureus and E. coli in this context becomes opportunistic thereby, causing genital tract infections. Staphylococcus from the index showed more sensitivity to Amoxicillin/clavulanate (95.4%/90.4%) compared to the partners (55.1%/73.5%) and more resistant to Ceftazidime (81.4%) compared to the partners (68.9%). LTNPs were 28(8.51%) among the index. HLA-B alleles: B*5701 (9.2%), B*5703 (4.6%) and B*5801(12.5%) were identified for viral control at late stage of HIV infection while A*1 (4.6%), and C*0701 (29.1%) were protective alleles observed. HLA-B*0702 (33.3%), B*4201/A*2301(4.6%) respectively were susceptible alleles associated with seroconversion among LTNPs.ConclusionThe microorganisms isolated from the index were associated with high viral loads and are independent makers to HIV-1 transmission among serodiscordant couples. Individuals associated with HLA class I alleles identified among LTNPs were those significantly associated with resistance and susceptible to HIV-1 infections.

HIV Viral Dynamic under Treatment with Intracellular Delay and Virus Decay as Interactive Parameters

Treatment with antiviral drugs for human immunodeficiency virus type 1 (HIV-1) infection causes a rapid reduction in plasma viral load. Viral decline occurs in several stages and provides information on important kinetic constants of virus replication in vivo and pharmacodynamic properties. We present a mathematical model that not only considers the intracellular phase of the viral life cycle, defined as the time between the infection of a cell and the production of new viral particles, but we also consider that this parameter together with the virus decay are interactive fuzzy numbers.

Regulation of the acetylcholine/α7nAChR anti-inflammatory pathway in COVID-19 patients

The cholinergic system has been proposed as a potential regulator of COVID-19-induced hypercytokinemia. We investigated whole-blood expression of cholinergic system members and correlated it with COVID-19 severity. Patients with confirmed SARS-CoV-2 infection and healthy aged-matched controls were included in this non-interventional study. A whole blood sample was drawn between 9–11 days after symptoms onset, and peripheral leukocyte phenotyping, cytokines measurement, RNA expression and plasma viral load were determined. Additionally, whole-blood expression of native alpha-7 nicotinic subunit and its negative dominant duplicate (CHRFAM7A), choline acetyltransferase and acetylcholine esterase (AchE) were determined. Thirty-seven patients with COVID-19 (10 moderate, 11 severe and 16 with critical disease) and 14 controls were included. Expression of CHRFAM7A was significantly lower in critical COVID-19 patients compared to controls. COVID-19 patients not expressing CHRFAM7A had higher levels of CRP, more extended pulmonary lesions and displayed more pronounced lymphopenia. COVID-19 patients without CHRFAM7A expression also showed increased TNF pathway expression in whole blood. AchE was also expressed in 30 COVID-19 patients and in all controls. COVID-19-induced hypercytokinemia is associated with decreased expression of the pro-inflammatory dominant negative duplicate CHRFAM7A. Expression of this duplicate might be considered before targeting the cholinergic system in COVID-19 with nicotine.

Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients

The ectodomain of gp41 is the target of potent binding and neutralizing antibodies (NAbs) and is being explored in new strategies for antibody-based HIV vaccines. Previous studies have suggested that the W164A-3S (3S) and EC26-2A4 (EC26) peptides located in the gp41 ectodomain may be potential HIV vaccine candidates. We assessed 3S- and EC26-specific binding antibody responses and related neutralizing activity in a large panel of chronic HIV-1-infected Portuguese individuals on ART. A similar proportion of participants had antibodies binding to 3S (9.6%) and EC26 (9.9%) peptides but the level of reactivity against 3S was significantly higher compared to EC26, except in the rare patients with double peptide reactivity. The higher antigenicity of 3S was unrelated with disease stage, as assessed by CD4+ T cell counts, but it was directly related with plasma viral load. Most patients that were tested (89.9%, N = 268) showed tier 1 neutralizing activity, the potency being inversely associated with plasma viral load. In the subset of patients that were tested for neutralization of tier 2 isolates, neutralization breadth was inversely correlated with plasma viral load and directly correlated with CD4+ T cell counts. These results are consistent with a role for neutralizing antibodies in controlling viral replication and preventing the decline of CD4+ T lymphocytes. Importantly, in patients with 3S-specific antibodies, neutralizing titers were inversely correlated with viral RNA levels and proviral DNA levels. Moreover, patients with 3S and/or EC26-specific antibodies showed a 1.9-fold higher tier 2 neutralization score than patients without antibodies suggesting that 3S and/or EC26-specific antibodies contribute to neutralization breadth and potency in HIV-1 infected patients. Overall, these results suggest that antibodies targeting the S3 and EC26 epitopes may contribute to reduce viral burden and provide further support for the inclusion of 3S and EC26 epitopes in HIV-1 vaccine candidates.

Covidaemia and its implications

Coronavirus disease 2019 (COVID-19) pandemic has taught many lessons to the medical fraternity. Academicians and the general population have been through phases of anxiety, panic, and trail and errors. The growing assumption at the onset of the pandemic that COVID infection may spread by blood has not found its roots deep enough for any clinical consequences. As all the symptoms of COVID relate to its local invasion at the alveolar level and its immunological sequelae, this article discusses the possibilities with the research available over the last 10 months. So far, the plasma viral load detected by reverse transcriptase polymerase chain reaction (RT-PCR) seems immaterial in comparison to the viral concentration from nasopharyngeal swabs. So the recommendations to prefer caesarean section for positive mothers, deferring blood donations by COVID patients, frequent antigen testing from blood serum and body fluids like breast milk or amniotic fluid, may really need to be given a second thought. Also, this article concludes about giving up the panic around the viremia-related possibility of vertical transmission from mother to fetus and other clinical implications of testing of blood for the same. This will help in saving the resources heavily to be used only selectively. Newborns in neonatal intensive care unit (NICU) may be permitted to be handled without gloves and using simple practices of handwashing, saving further resources and reducing neonatal infections.

Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals

HIV-1 Nef plays an essential role in enhancing virion infectivity by antagonizing the host restriction molecule SERINC5. Because Nef is highly polymorphic due to the selective forces of host cellular immunity, we hypothesized that certain immune-escape polymorphisms may impair Nef’s ability to antagonize SERINC5 and thereby influence viral fitness in vivo. To test this hypothesis, we identified 58 Nef polymorphisms that were overrepresented in HIV-infected patients in Japan sharing the same HLA genotypes. The number of immune-associated Nef polymorphisms was inversely correlated with the plasma viral load. By breaking down the specific HLA allele-associated mutations, we found that a number of the HLA-B*51:01-associated Y120F and Q125H mutations were most significantly associated with a reduced plasma viral load. A series of biochemical experiments showed that the double mutations Y120F/Q125H, but not either single mutation, impaired Nef’s ability to antagonize SERINC5 and was associated with decreasing virion infectivity and viral replication in primary lymphocytes. In contrast, other Nef functions such as CD4, CCR5, CXCR4 and HLA class I downregulation and CD74 upregulation remained unchanged. Taken together, our results suggest that the differential ability of Nef to counteract SERINC5 by naturally occurring immune-associated mutations was associated with the plasma viral load in vivo.