Current HIV Research - Volume 19, Issue 3, 2021

Aims: To evaluate the effectiveness of telemedicine in the clinical management of children living with HIV/AIDS in resource-limited settings Background: Telemedicine is an important mechanism for service delivery in health care settings, both in resource-rich and resource-poor settings. Such service delivery mechanisms have shown to be associated with virologic suppression and higher CD4 counts. These services are also associated with improved access, shorter visiting times, and higher patient satisfaction. Objective: We designed the present two-group comparison study to compare the clinical evaluation and management of children in the anti-retroviral therapy (ART) centres linked to telemedicine facility with those who are not linked to this facility in Maharashtra, India. Methods: We analysed clinical records from six ART centres in Maharashtra; of these, 250 children were in the linked ART centres and 301 were in the non-linked ART centres. The outcomes were classified according to investigations, management, and monitoring. For management, we evaluated: 1) Initiation of cotrimoxazole prophylaxis; 2) Children not initiated on ART when required; 3) ART regime after appropriate investigations; and 4) Change of regime (if immunologically indicated). For monitoring, we assessed the haematological monitoring of children on ART. Results: The mean (SD) ages of children in linked and non-linked ART centres were 10.8 (4.6) and 10.9 (4.6) years, respectively (p=0.80). After adjusting for individual and structural level variables, physical examination (OR: 2.0, 95% CI; 1.2, 3.2), screening for tuberculosis (OR: 12.9, 95% CI: 2.0, 82.9) and cotrimoxazole prophylaxis were significantly more likely in the linked centres compared with non-linked centres (OR: 1.8, 95% CI: 1.4, 2.2). A higher proportion of children eligible for ART were not initiated on treatment in the non-linked centres compared with linked centres (26% vs. 8%, p=0.06). Children were less likely to be initiated on zidovudine-based regimens without baseline haemoglobin or with baseline haemoglobin of less than 9 gm% in linked centres (OR: 0.7, 95% CI: 0.6, 0.8). Similarly, children in the linked centres were less likely to have been started on nevirapine-based regimens without baseline liver enzymes (OR: 0.8, 95% CI: 0.7, 0.9). Conclusion: Thus, the overall clinical management of Children Living with HIV/ AIDS (CLHA) was better in ART centres linked with the telemedicine initiative compared with those who were not linked. Children in the linked ART centres were more likely to have a complete baseline assessment (physical, hematological, radiological, and screening for TB); the presence of a pediatrician in the centres was helpful.

Background: Human immunodeficiency virus infection is a recognized risk factor for premature atherosclerosis in children and adolescents. However, the atherosclerotic process in uninfected children exposed in utero to the virus and antiretroviral therapy is less clear. Objective: To determine the potential cardiovascular risk associated to this in utero milieu exposition. Material and Methods: A total of 115 individuals were studied (77 in the sample group and 38 in the controls). Eighteen analytical mediators involved in the atherogenic pathways (metabolic dysregulation, inflammation, and prothrombotic state) were analyzed. The carotid intima-media thickness, which is a subclinical marker of atherosclerosis, was also measured. Results: No significant statistical differences were identified between the sample and control groups, either in the biochemical or the echographic markers. Conclusion: In utero exposure to the HIV virus and antiretroviral therapy in uninfected children and adolescents is not correlated to accelerated atherosclerosis.

Background: The diagnosis of HIV infection is important among different groups. Moreover, combination antiretroviral therapy is used to treat HIV-1, but it cannot eradicate the infection. Thus, the development of therapeutic vaccines, along with antiretroviral therapy, is recommended. This study evaluates the values of four HIV proteins as antigen candidates in therapeutic vaccine design as well as a possible diagnostic marker for HIV infection in humans. Methods: In this study, the HIV-1 Tat and Rev regulatory proteins and structural Gp120 and p24 proteins were generated in E. coli expression system. Their immunogenicity was evaluated in BALB/ c mice using homologous and heterologous prime/boost strategies. Moreover, the detection of anti- HIV IgG antibodies against these recombinant proteins was assessed in untreated (Naïve/ HIV-infected), treated, and drug-resistant patients compared to the healthy (control) group as a possible diagnostic marker for HIV infection. Results: In humans, our results showed that among HIV-1 proteins, anti-Gp120 antibody was not detected in treated individuals compared to the healthy (control) group. The levels of anti-Gp120 antibody were significantly different between the treated group and Naïve as well as drug-resistant subjects. Moreover, the level of anti-p24 antibody was significantly lower in the treated group than the Naive group. In mice, the results of immunization indicated that the Rev antigen could significantly induce IgG2a, IgG2b, and IFN-γ secretion aimed at Th1 response as well as Granzyme B generation as CTL activity in comparison with other antigens. Furthermore, the heterologous DNA prime/ protein boost regimen was more potent than the homologous regimen for stimulation of cellular immunity. Conclusion: Briefly, the levels of both anti-Gp120 and anti-p24 antibodies can be considered for the diagnosis of the HIV-infected individuals in different groups compared to the healthy group. Moreover, among four recombinant proteins, Rev elicited Th1 cellular immunity and CTL activity in mice as an antigen candidate in therapeutic vaccine development.

Background: The latent reservoir of HIV-1 is a major barrier to achieving the eradication of HIV-1/AIDS. One strategy is termed “shock and kill”, which aims to awaken the latent HIV-1 using latency reversing agents (LRAs) to replicate and produce HIV-1 particles. Subsequently, the host cells containing HIV-1 can be recognized and eliminated by the immune response and anti-retroviral therapy. Although many LRAs have been found and tested, their clinical trials were dissatisfactory. Objective: To aim of the study was to investigate how resveratrol reactivates silent HIV-1 transcription and assess if resveratrol could be a candidate drug for the “shock” phase in “shock and kill” strategy. Methods: We used established HIV-1 transcription cell models (HeLa-based NH1 and NH2 cells) and HIV-1 latent cell models (J-Lat A72 and Jurkat 2D10 cells). We performed resveratrol treatment on these cell lines and studied the mechanism of how resveratrol stimulates HIV-1 gene transcription. We also tested resveratrol’s bioactivity on primary cells isolated from HIV-1 latent infected patients. Results: Resveratrol promoted HIV-1 Tat protein levels, and resveratrol-induced Tat promotion was found to be dependent on the AKT/FOXO1 signaling axis. Resveratrol could partially dissociate P-TEFb (Positive Transcription Elongation Factor b) from 7SK snRNP (7SK small nuclear Ribonucleoprotein) and promote Tat-SEC (Super Elongation Complex) interaction. Preclinical studies showed that resveratrol potentiated Vorinostat to awaken HIV-1 latency in HIV-1 latent infected cells isolated from patients. Conclusion: We found a new mechanism of resveratrol stimulating the production of HIV-1. Resveratrol could be a promising candidate drug to eradicate HIV-1 reservoirs.

Background: We investigated if initiating preventive care against HIV vertical transmission by antenatal HIV screening is independent of the patients’ source of financial reimbursement for the care received in sub-Saharan Africa (SSA). Methods: Using information from the WHO’s Global Health Expenditure Database and the Demographic Health Surveys Database for 27 sub-Saharan countries, we used Spearman’s correlation and adjusted survey logistic regression to determine the potential relationship between enrollment in health insurance and the likelihood that expectant mothers would be offered antenatal HIV screening. Results: We found that expectant mothers covered by health insurance were more than twice as likely to be offered antenatal screening for HIV compared to the uninsured. The likelihood differed by the type of insurance plan the expectant mother carried. Discussion: Health insurance is more of a financial tool that this study finds to be necessary to boost the uptake of preventive and therapeutic HIV care in SSA. Conclusion: The ensuing disparity in receiving proper care could hinder the goals of 90-90-90 and the forthcoming 95-95-95 plan in SSA.

Background: The improvements in HIV infection therapy and the large availability of antiretroviral drugs have led to an increased survival among HIV infected people, and simultaneously to a raised morbidity and mortality due to not-AIDS-related events in this group compared to the general population. An increased systemic inflammation and a persistent immune activation play a pivotal role in determining high rates of non-AIDS comorbidities. In the last years, many natural or synthetic immunomodulatory molecules acting by different mechanisms have been conceived. Pidotimod is a synthetic dipeptide molecule showing immunomodulatory properties. The aim of this pilot study was to evaluate the effects of Pidotimod supplementation on residual inflammation in HIV infected population. Methods: Forty HIV positive individuals under cART were enrolled: 30 were treated with Pidotimod supplementation (study group) and 10 served as control group (without Pidotimod supplementation). For all participants, Cystatin C, PCR, ESR, microalbuminuria, TNF-α, INF-γ, IL-4, IL-10, IL1β, IL-18 and IL-2 were measured at enrolment (T0), 4 weeks after of Pidotimod supplementation (T1), and 4 weeks after completing supplementation (T2). Results: In HIV positive participants treated with Pidotimod, the evaluation of cytokine levels showed that IL-10, IFN gamma, and IL-4 were significantly higher at enrolment compared to the control group. The increase under Pidotimod treatment persisted after supplementation suspension, while the pro-inflammatory cytokines levels were reduced. Salivary IgA also increased during 4 weeks of supplementation and persisted at 4 weeks after completing supplementation. On the other hand, the Cystatin C and microalbuminuria levels decreased over time, at a greater extent the Cystatin C serum levels. Conclusion: The study findings showed that the HIV population receiving Pidotimod achieved a rebalancing of pro-inflammatory and anti-inflammatory cytokines as well as a significant reduction in cystatin C levels. The treatment further allowed for an increase in salivary IgA levels at all the analyzed times, as a secondary event to a remodulation of the immunological status obtained with pidotimod. This approach could represent a new way to design new intervention strategies aimed at improving the persistent immune activation status in the virologically suppressed HIV population.

Background: HIV transmission during pregnancy and breastfeeding among serodiscordant heterosexual couples represents an ongoing barrier to the elimination of vertical transmission of HIV-1 infection in Canada. Objective: To report a case of vertical HIV transmission during breastfeeding and examine the prevalence of risk factors for HIV transmission in the pregnancy and postpartum periods among serodiscordant couples where the male partner is HIV positive and female partner HIV negative. Methods: Case report and retrospective chart review of HIV-serodiscordant pregnant couples over an eight-year period in Edmonton, Canada. Results: We report a case of maternal primary HIV infection during the postpartum period and vertical transmission to a nursing infant that went undetected until the infant presented with AIDS. We also report a series of 41 serodiscordant pregnant couples identified by our public health nurse between 2008 and 2016. Among HIV-infected male partners, 20 (49%) had a detectable viral load (VL) during their partner’s pregnancy and during breastfeeding, with median peak VL 4,700 copies/mL (range 49-120,000) and 5,100 copies/mL (range 40-120,000) during pregnancy and breastfeeding, respectively. None of the female partners seroconverted during pregnancy, but three seroconverted at 1.8, 2.4, and 6.9 years after delivery. No vertical transmission occurred. Conclusion: Despite concerted attempts to minimize HIV transmission during pregnancy and breastfeeding in our well-resourced setting, residual transmission risk remains due to non-suppressed viral load within many HIV-serodiscordant pregnant couples.

Background: Antiretroviral therapy (ART) has led to a decline in autoimmune diseases but lacks studies on its effect on autoantibodies. Methods: It is a cross-sectional study with archived samples from 100 paired HIV-1 infected ART naïve and experienced individuals and 100 prospectively collected matched blood-donor controls. Antinuclear antibody, IgG anticardiolipin antibody, IgM and IgG β2 glycoprotein-1 antibodies, and total IgG levels were detected. Results are expressed as mean with standard deviation (SD), median, percentage positivity, and a p<0.05 is considered significant. The study was approved by the Institutional Review Board. Results: The median viral load of the treatment naïve samples was 4.34 Log copies/mL, while all were virally suppressed post ART with a median duration of treatment for 12 months (range: 3-36 months). The percentage of antinuclear antibody positivity was 5% among ART naïve and controls, with a decrease of 2% post ART (p= 0.441). The positivity for anti-cardiolipin antibody was 15% among ART naïve while none of the ART experienced or controls were positive (p<0.05). IgM β2 glycoprotein-1 were 4%, 1% and 3% among ART naïve, treated and controls, respectively (p<0.05). IgG β2 glycoprotein-1 was 2% among ART naïve while none of the treated and controls were positive (p<0.05). The mean total IgG level among ART naïve, experienced, and controls were 21.82 (SD 6.67), 16.91 (SD 3.38), 13.70 (SD 2.24) grams/Litre, respectively (p<0.05). Conclusion: ART has a significant effect on IgG anti-cardiolipin antibody and total IgG but only a marginal effect on ANA, IgM, and IgG β2 glycoprotein-1 antibodies.

Background: The clinical spectrum of SARS-CoV-2 infection may vary from simple colds to a severe acute respiratory syndrome, metabolic acidosis, septic shock, and multiple organ failure. Current evidence indicates that the risk of severe illness increases with age, in the male sex, and with certain chronic medical problems. Many people living with HIV have other conditions that increase their risk. Case presentation: In the first 3 months of the pandemic, four patients with HIV were hospitalized in our clinic because of COVID-19. The disease severity was mild in two patients with normal CD4+ T count. However, one patient with a low CD4+T count died and the other developed retinal detachment one month after discharge. The deceased patient had a malignancy. Conclusion: In this study, the effect of the immunological status of the patients on the course of COVID-19 and the developing vascular complications was evaluated in 4 patients with HIV.