Current HIV Research - Volume 19, Issue 6, 2021

A number of different viral families have developed convergent methods to infect cells. Class I fusion proteins are commonly used by members of Arenaviridae, Coronaviridae, Filovirdae, Orthomyxoviridae, Paramyxoviridae, and Retroviridae. Class I viral fusion proteins are trimers that are involved in recognizing the cellular receptor, with a region that is responsible for fusing the viral and target cell membranes. During the fusion process, the fusion region folds into a six-helix bundle (6 HB) which approximates the two membranes leading to fusion. For Human Immunodeficiency Virus (HIV), the gp41 subunit is responsible for the formation of this 6 HB. The fusion inhibitor drug enfuvirtide, or T20, is the only US Food and Drug Administration and European Medicines Agency approved drug which targets this crucial step and has been widely used in combination regimens for the treatment of HIV since March 2003. In this review, we describe the current state of peptide-based fusion inhibitors in the treatment of HIV, and review how the field of HIV research is driving advances in the development of similar therapeutics in other viral systems, including the Severe Acute Respiratory Syndrome (SARS) coronaviruses.

HIV/AIDS continues to be a major global public health issue, affecting multiple organs, such as the eyes. With the advent of Highly Active Antiretroviral Therapy (HAART), the incidence has dropped but HIV ocular complications still remain a major cause of vision impairment in HIVpositive individuals. Since modern medical interventions nowadays can change this previously fatal infection into a chronic disease and enable people living with HIV for relatively long and healthy lives, recent studies update the incidence of HIV-related ocular manifestations, which has reached 70% among HIV patients. The primary ocular disorders induced by HIV are various and the clinical ocular findings are similar, which may be a problem to diagnose in the setting of disease. In our discussion, these complications are classified by etiology, for example noninfectious microvasculopathy resulting from direct invasion of the HIV, HIV-associated opportunistic infections caused by a virus, such as cytomegalovirus and varicella-zoster virus, fungus for example, candida and cryptococcus, bacteria like mycobacterium, parasites, such as toxoplasma and pneumocystis, and other pathogens, and infiltration lesions like lymphoma and Kaposi sarcoma. In order to get a better understanding of HIV ocular complications, we focus on HIV-related ocular complications in the HAART era with an emphasis on current incidence, clinical manifestations, ocular examination findings, differential diagnosis, treatment, and prognosis. In addition, we discuss the possibility of virus reservoir in the eyes, which makes HIV-related oculopathy still ubiquitous even after successful systemic treatment.

Background: In line with global standards and progress made in Prevention of Motherto- Child Transmission (PMTCT), an assessment of the outcome of Early Infant Diagnosis in northern Nigeria is necessary to evaluate progress towards zero Human immunodeficiency Virus (HIV) infection among children. Objectives: This study assessed the infection rate and risk factors for mother-to-child HIV transmission among HIV-exposed children in Kano, northwest Nigeria. Methods: Using a retrospective cohort design, pregnant HIV-positive women and their exposed infants were recruited over a period of six years (2010 to 2016). Participants were enrolled during pregnancy or at delivery in the PMTCT clinic of a tertiary health facility in Kano, Nigeria. The main outcomes for the study were Early infant diagnosis positivity for HIV at 6 weeks and risk factors for positivity. Results: Of the 1,514 infants studied, early infant diagnosis was positive for HIV among 13 infants (0.86%). Infants whose mothers did not have antiretroviral therapy (adjusted Prevalence Ratio aPR = 2.58, 95%CI (1.85- 3.57)), who had mixed feeding (aPR = 12.06, 95%CI (9.86- 14.70)), and those not on antiretroviral prophylaxis (aPR = 20.39, 95%CI (16.04- 25.71)) were more likely to be infected with HIV. HIV-exposed infants on nevirapine and zidovudine prophylaxis were 95% and 74%, respectively, less likely to be infected with HIV. Conclusion: HIV infection rate remains high among HIV-exposed infants whose mothers did not receive PMTCT services. Scaling up proven interventions of early commencement of antiretroviral treatment for mothers, adherence to antiretroviral prophylaxis, and avoidance of mixed feeding among HIV-exposed infants would protect future generations from HIV infection.

Background: Antiretroviral therapy (ART) non-adherence and methamphetamine use are associated with higher HIV drug resistance prevalence. How they affect drug resistance mutations accumulation is less studied. Objective: We assessed factors associated with drug resistance mutations accumulation. Methods: We evaluated HIV chronically-infected patients from a clinic-based research cohort on first-line ART regimens with genotype results within 30 days of baseline. Methamphetamine use and ART adherence were self-reported at each study visit. High ART adherence was defined as 0-5% missed doses in the last 30 days. Results: One-hundred twenty-five patients contributed 496 study visits. At baseline, 81% of patients reported high ART adherence; 90% reported no methamphetamine use in the prior 4 months, 8% used monthly or less and 2% used daily or weekly. Methamphetamine users and non-users had similarly high ART adherence (p=0.93). Adjusted incidence rate ratio (aIRR) of drug resistance mutations accumulation was 2.04 (95% CI 0.64, 6.46) for daily/weekly users and 1.71 (95% CI 0.66, 4.42) for patients with monthly or less users, compared to non-users. aIRR was 0.71 (95% CI 0.44, 1.15) with >5-10% missed ART doses and 1.21 (95% CI 0.80, 1.83) with >10% missed doses compared to 0-5% missed doses. Conclusion: We found no strong evidence for the effect of methamphetamine use and ART adherence on drug resistance mutations accumulation. Research cohort patients may have been more engaged in care and treatment adherent than non-cohort patients. Our findings suggest methamphetamine use might not lead to treatment failure among HIV patients who are otherwise engaged in care.

Background: Improved survivorship among persons living with HIV translates into a higher risk of medical comorbidities. Objectives: We assessed the association between the intersection of physical (HIV) and mental health (psychiatric) conditions and intermediate outcomes. Methods: This was a cross-sectional study of the Medical Expenditure Panel Survey (MEPS)- Household Component between 1996 and 2016. We created four groups for persons aged ≥18: (1) HIV + psychiatric comorbidity, (2) HIV, (3) psychiatric comorbidity, and (4) no-HIV/no-psychiatric comorbidity. We compared the burden of medical comorbidities (metabolic disorders, cardiovascular disease, cancers, infectious diseases, pain, and substance use) among groups using chisquare tests. We used logistic regression to determine the association between group status and medical comorbidity. Results: Of 218,133,630 (weighted) persons aged ≥18, 0.18% were HIV-positive. Forty-three percent of the HIV group and 19% of the no-HIV group had psychiatric comorbidities. Half of the HIV+ psychiatric disorder group had at least one medical comorbidity. Compared to the no- HIV/no-psychiatric comorbidity group, the HIV + psychiatric comorbidity group had the highest odds of medical comorbidity (OR= 3.69, 95% CI = 2.99, 4.52). Conclusion: Persons presenting with HIV + psychiatric comorbidity had higher odds of medical comorbidities of pain, cancer, cardiovascular disease, substance use, metabolic disorders and infectious diseases, beyond that experienced by persons with HIV infection or psychiatric disorders, independently. Future research will focus on the mediating effects of social determinants and biological factors on outcomes such as the quality of life, cost and mortality. This will facilitate a shift away from the single-disease framework and compress morbidity of the aging cohort of HIV-infected persons.

Background: Human Immune Deficiency Virus (HIV), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infections constitute a global health concern. They share common modes of transmission, increasing the likelihood of co-infection. Co-infection accelerates viral replication, promotes the progression of chronic liver diseases and challenges antiviral therapy. There are no available data addressing the magnitude of chronic viral hepatitis co-infection in people living with HIV in Egypt. Nor is there a mandate for HCV/HBV screening. This cross-sectional study provides needed data on HBV and/or HCV co-infection in Egyptian people living with HIV. Subjects and Methods: The study was conducted at the HIV clinic in Alexandria Fever Hospital. The investigation included 168 confirmed HIV cases. All cases were interviewed and tested for HCV-Ab and HBsAg by ELISA. Results: There were 52 (31%) persons who were anti-HCV positive. 40 of them had detectable HCV RNA (76.9%). HIV/HCV co-infection was significantly higher among males (40.7%) compared to only (10.9%) among females (OR = 3). History of imprisonment (OR = 4.84, CI: 1.33-17.62), accidental puncture with protruding needle contaminated with blood (OR = 3.35, CI: 0.99-11.72), alcohol use (OR = 3.03, CI: 1.13-8.09) and male gender (OR = 2.96, CI: 0.99-8.88) were all significant predictors for HIV/HCV co-infection. On the other hand, HIV/HCV co-infection was inversely associated with high education level (OR = 0.28, CI: 0.10-0.76). HBsAg was detected in 4 (2.4%), and anti-HBc in 49 (29.2%) of HIV patients. Previous HBV infection (positive anti-HBc/negative anti-HBs) was significantly associated with a history of female genital mutilation circumcision, injection drug use, invasive procedures, non-specific fatigue and HCV-Ab seropositivity. Conclusion: Egyptian people living with HIV have an increased frequency of HCV antibody and HCV infection compared to the general population indicating a higher risk of infection and suggest a higher risk of HCV exposure. Past or present HBV co-infections are also elevated. Routine screening of these viruses in the management protocol of people living with HIV in Egypt is recommended.

Background: HIV-related stigma poses a crucial barrier to HIV therapy and prevention worldwide. Stigma taking place in healthcare settings has also been a global challenge for years. Objective: To measure HIV-related stigma among health care facilities in Baoan, Shenzhen and to take decision regarding stigma-reduction intervention. Methods: We conducted a cross-sectional survey in Shenzhen Baoan Women's and Children's Hospital, China in February 2019. We collected data on HIV-related stigma from 207 hospital staff randomly selected for an anonymous survey online by a standardized questionnaire. We analyzed the influence factors on HIV-related stigma taking place in health facilities using the statistical method. Results: The percentages of worry expressed when touching clothing, dressing wound, and drawing blood for PLWH were 60.9%, 84.5%, and 82.6%, respectively. 76.3% of respondents reported at least one form of extra precautions taken during service provision to PLWH. Younger hospital employees with less working experience were more likely concerned about occupation risk of HIV infection (P<0.05). Single workers with lower education and no experience of training on HIV-related stigma were prone to discriminatory opinions against PLWH (P<0.05). Conclusion: HIV-related stigma in health facilities remains a significant challenge, and evidence- based interventions at both systematic and individual levels are needed for improvements.

Background: This paper reports the synthesis, Non-nucleoside reverse transcriptase inhibitory (NNRTIs) activity and computational studies of 2-((4-chloro-2-subtitutedphenoxy) methyl)-4-(furan-2-ylmethylene)-1-substituted Pyridine/-pyrimidine-1H-imidazol-5(4H)-ones. Methods: The imidazol-5-one analogs were synthesized by conventional method and characterized by FT-IR, NMR and mass spectral data. All compounds were evaluated for in-vitro NNRTI activity by using reverse transcriptase (RT) assay kit (Roche). The in-silico docking studies were conducted on RT enzyme to investigate binding site interactions of synthesized compounds. The MMGBSA method was also used to calculate the binding free energy between the inhibitors and RT enzyme. The MD simulation was further performed for the apo form of the RT enzyme and docked complex of compound A6-RT enzyme to better understand the stability of the protein-ligand complex. Results: The bioactivity analysis revealed that most of the synthesized compounds showed significant inhibitory activity against RT enzyme and the IC50 value was found to be in the range of 1.76-3.88 μM. The computational studies suggest that the docked compounds form the H-bonding with amino acid residue Lys101 and hydrophobic interactions with amino acid residues Tyr188, Tyr181, Trp229, and Tyr318, which act as the primary driving forces for protein-ligand interaction. Conclusion: The reported imidazol-5-one analogs can act as lead for further development of prospective RT inhibitors.

Background: The current COVID-19 pandemic has attracted great attention from the medical world. In the past year, there have been reports of missed or delayed treatments for conditions that mimic COVID-19. The main symptoms caused by SARS-CoV-2, such as fever and cough, belong to different clinical conditions. It is of the utmost importance that the diagnostic thinking used to analyze data and information to reach a COVID-19 diagnosis does not overlook the plethora of different diagnoses related to these symptoms. Case Report: The aim of this work is to present the clinical case of a patient having unrecognized HIV infection with a 4-week history of fever, cough, and hypoxia. When tests were allowed to highlight HIV-related immunodeficiency status, a CMV assay was performed in order to evaluate opportunistic pneumonia. Through this, diagnosis of HIV combined with CMV pneumonia was made, thus excluding COVID-19 respiratory insufficiency. Conclusion: The diagnosis of the two conditions in the COVID-19 era is challenging due to overlapping clinical and radiological features and limitations of current diagnostic assays. This causes clinical implications due to diagnostic delays.