Current HIV Research - Volume 19, Issue 4, 2021

Aim: This study aims to investigate the prevalence and drug-resistance M. tuberculosis isolated from HIV seropositive individuals in Tehran, Iran. Background: Human immunodeficiency virus (HIV) is one of the most important risk factors for developing active tuberculosis (TB). Objective: The objective is to determine the rate of transmission and drug-resistant M. tuberculosis (MTB) strains isolated from HIV seropositive patients in Tehran province, Iran. Methods: This study consecutively enrolled 217 TB/HIV coinfected patients from April 2018 to August 2019 at Emam Khomeini referral hospital and 5 other health centers in Tehran province. The isolates were genotyped using 15 loci Mycobacterial interspersed repetitive unit-variable number tandem repeats (MIRU-VNTR). Minimum inhibitory concentration (MIC) was determined for 6 drugs. In addition, mutations were assessed in rpoB, katG, inhA, and ahpC genes using Reverse Blot Hybridization Assay System. Results: A 20 (9.2%) patients were culture-positive for M. tuberculosis and typed by MIRU-VNTR, 13 (65%) strains formed 5 clusters, but 6 (30%) isolates had a unique pattern. The total Hunter– Gaston discrimination index (HGDI) for all 15 loci was 0.846, and the cluster size was 2 to 4 patients. The estimated proportion of recent transmission was 45%. The mutation was identified in 1 isolate, lost inhAW1 and mutation in MT1 loci, which was resistant to isoniazid (INH). Moreover, 1 (5%) and 3 (15%) isolates were resistant to INH and ethambutol (EMB), respectively, of which 1 was resistant to INH and EMB. Conclusion: The transmission rate of TB in HIV patients was relatively high; however, the prevalence of drug-resistant strains and TB infection in females was insignificant in this study (p < 0.05); none of the isolates was MDR strains.

Background: The prevention of AIDS among undergraduates in Wuhan is a public health priority. An important strategy for students to prevent AIDS is to establish correct moral concepts and cultivate a healthy lifestyle. Introduction: Through the investigation of MSM and non-MSM population in college students, this study seeks for possible influencing factors and solutions for AIDS prevention in colleges and universities. Methods: This study was carried out in 15 universities in Wuhan. We recruited 127 MSM students through peer promotion, and 510 non-MSM students were selected by random cluster sampling. The two groups were investigated by anonymous questionnaire, and the questionnaire information was statistically analyzed. Results: The awareness rate of AIDS-related knowledge among MSM students was 90.8%, while that among non-MSM students, it was 64.6%; neither meets the national requirements. The self- -recognition of MSM undergraduates was 95.0%. Among the 497 non-MSM undergraduates, 65.4% were willing to make friends with the MSM undergraduates. There were statistical differences in the social discrimination attitudes of those who knew AIDS-related knowledge (P<0.01), and the attitudes of those with knowledge of AIDS were more positive. Conclusion: The MSM students reported a high incidence of high-risk sexual behaviors and a gap between knowledge and behaviors. This study focuses on the comparison of the characteristics of knowledge, attitude, and behavior on AIDS between the two groups of people. AIDS prevention in colleges and universities requires a new way of thinking.

Objective: The study aimed to assess the role of TE in HIV-infected patients with NAFLD. Methods: HIV-infected patients undergoing ART were enrolled between August 2016 and February 2017, following the inclusion criteria: ≥18 years with undetectable HIV viral load. Exclusion criteria included pregnancy, alcohol intake ≥20g/day and co-infection with hepatitis B or C. Patients underwent an abdominal US to diagnose liver steatosis. Significant fibrosis (≥F2) was considered when APRI>1.0, FIB4>3 and liver stiffness ≥7.1kPa. Subjects with TE ≥7.1kPa were prescribed a liver biopsy and the NAFLD Scoring System ≥3 was considered as a diagnosis of NASH. The poisson regression model was used to identify factors associated with liver steatosis. Results: 98 patients were included. The mean age of the subjects was 49±11 years and 53 (54.1%) were males. Liver steatosis was diagnosed in 31 patients (31.6%) and was independently associated with male sex (PR= 2.18) and higher BMI (PR=1.08). Among the 31 patients with NAFLD, 26 showed results for TE, APRI and FIB4. The prevalence of significant fibrosis assessed by TE, APRI and FIB4 was 26.9%, 6.4% and 3.2%, respectively. Seven patients (26.9%) had a TE result ≥7.1kPa, which was associated with higher triglyceride levels, FIB4 score and CAP values. Liver biopsy was perfomed on six of those with TE ≥7.1kPa and NASH was found in 5 (83.3%) and liver fibrosis without NASH in one. Conclusion: NAFLD prevalence in HIV-infected patients is higher than the general population. TE ≥7.1kPa was not able to diagnose significant fibrosis but accurately detect a subgroup of patients at a high risk for NASH among HIV monoinfected individuals with steatosis.

Background: Human immunodeficiency virus type-1 (HIV-1) infection is the reason for the epidemic of acquired immunodeficiency syndrome (AIDS). The development of HIV-1 fusion inhibitors has gained increasing attention as they were found to be effective in the early stage of HIV-1. DNA G-quadruplex-based inhibitors have been found to interact with HIV-1 envelope glycoprotein, showing anti–HIV-1 fusion activity. C-peptide-derived molecules with Met-Thr terminal also showed potent anti-fusion activity; the Met-Thr dipeptide adopted a hook-like structure (termed MT hook) in the hydrophobic pocket to “anchor” inhibitors to the N-terminal heptad repeat (NHR) of HIV-1 envelope glycoprotein gp41. Objective: Our work was aimed to conjugate MT hooks to the 5'-terminal ends of DNA quadruplex- based inhibitor and demonstrate its biophysical characterization and anti–HIV-1 fusion activity. Methods: A 6-aminohexanol phosphonamidite was utilized in solid synthesis for the conjunction of oligodeoxynucleotide and MT dipeptide. Hydrophobic groups were introduced by a nucleoside analogue from the base site. Circular dichroism spectrum and native polyacrylamide gel electrophoresis were used to confirm the helix formation. A cell-cell fusion assay was carried out to test the anti-fusion activity. Results: The conjugate G1 showed improved anti-cell-cell fusion activity than quadruplex without MT hook. The MT hook did not affect the oligodeoxynucleotide (ODN) G-quadruplex assembly. It was also proved that G1 could effectively interfere with endogenous 6-helical bundle (6HB) formation between the N-terminal heptad repeat N36 (NHR) and the C-terminal heptad repeat C34 (CHR) during virus fusion course. Conclusion: In this work, a conjugate of DNA-oligopeptide was successfully synthesized. The conjugation of MT hook did improve the anti-fusion activity of DNA G-quadruplex-based inhibitors. Our results can provide information regarding structure-activity relationships of DNA helix-based inhibitors and a reference for the follow-up experimental studies.

Aim: This study aimed to analyze the association between any past-month cannabis use and advanced liver fibrosis. Background: Cannabinoid receptors play a role in acute and chronic liver injury, but human studies addressing the impact of cannabis use on liver fibrosis have shown mixed results. Objective: The objective of this study was to explore and estimate the association between pastmonth cannabis use and advanced liver fibrosis (ALF) in a cohort of Russian HIV-positive individuals with heavy alcohol use and a high prevalence of hepatitis C virus (HCV) coinfection. Methods: Baseline data were analyzed from participants of the ZINC study, a trial that enrolled HIV-positive Russian patients without prior antiretroviral therapy. Cannabis use during the prior month was assessed at study entry. ALF was defined as FIB-4>3.25 and APRI>1.5. Transient elastography was used to detect advanced liver fibrosis among participants with FIB-4 values in the intermediate range (between 1.45 and 3.25). Results: Participants (n=248) were mostly male (72.6%), young (median age of 33.9 years), infected with HCV (87.9%), and did not have advanced immunosuppression (median CD4 count 465). Cannabis use was uncommon (12.4%), and the prevalence of advanced liver disease was 21.7%. The prevalence of ALF was similar among those who used cannabis compared to those who did not (25.8% vs. 21.7%). We were unable to detect an association between cannabis use and ALF (adjusted odds ratio: 1.28, 95% confidence interval: 0.53-3.12, p=0.59) in logistic regression models adjusting for age, sex, heavy drinking, BMI, and CD4 cell count. Conclusion: In this exploratory study among HIV-positive heavy drinking Russians, we did not detect an association between recent cannabis use and ALF. Larger scale studies, including more participants with cannabis use, are needed to examine this relationship further.

Background: Chronic immune activation is one of the most widely recognized hallmarks of HIV infection. T-cells that express CD38+ and HLA-DR+ show poor proliferative potential, signal transduction, and increased apoptotic potential. This affects HIV pathogenesis and its outcome and further complicates with a coinfection like HBV. Methods: Study Design: cross-sectional. Blood samples were collected and analyzed for virological markers using ELISA for HBeAg and RT-PCR for HIV Viral load. Chronic immune activation markers of CD8+ and CD4+ T cells were measured by Flow cytometry for both HIV and HBV. Results: There was a significant increase in HBV replication shown by higher HBV DNA (p=0.002), a higher proportion of HBeAg (p=0.0049), and lower CD4 counts (p=0.04) among HIV/HBV coinfected individuals, compared to the monoinfected groups. The frequencies of CD4+ CD38+ HLA-DR+ and CD8+ CD38+ HLA-DR+ in the HIV/HBV coinfection were significantly higher than HBV monoinfected group (P< 0.0001) and in the HIV monoinfected group (P < 0.0001). The Liver fibrosis score APRI and FIB-4, were higher in the coinfected group compared with HBV monoinfected group (0.67 vs. 0.25, p = 0.0085; 3.48 vs. 0.98, p = 0.0026) respectively. The cytokine levels of IL-17, Fas-L,TNF -α, IL-10, IL-2 and Granzyme B were also measured and compared among the study groups. Conclusion: Our data suggest that HIV probably influences immune activation of CD4+ and CD8+ T cells and this may play a significant role in accelerating the disease outcome among HIV/HBV coinfected individuals.

Background: There is growing evidence that polymorphisms in chemokine and chemokine receptor genes influence susceptibility to HIV infection and disease progression. However, not much is documented about the influence of these polymorphisms in HIV serodiscordant couples in Cameroon. Objective: The objective of this study therefore was to determine the prevalence and the effect of the polymorphisms of CCR5-Δ32, CCR5 promoter 59029 A/G, CCR2-64I and SDF1-3′A gene in HIV serodiscordant couples in comparison to HIV negative seroconcordant and HIV positive seroconcordant couples in Yaoundé-Cameroon. Methods: A total of 96 couples were recruited from five hospitals, of which 60 couples were HIV serodiscordant (test group), 18 HIV negative seroconcordant and 18 HIV positive seroconcordant couples were used as controls. Their genotypes for CCR5-Δ32, CCR5 promoter, CCR2 and SDF1 were analyzed using polymerase chain reaction (PCR) and restriction fragment length polymorphism. Results: The allelic frequencies of these genes in the studied population were: 0%, 26.30%, 15.30% and 1.62% respectively for CCR5-Δ32, CCR5 promoter, CCR2 and SDF1. The frequency of the combination of CCR5 promoter and SDF1- (A/A+ G/G) wild-type genotype was higher in HIV-infected partners (82.92%) compared to uninfected partners (56.1%) in HIV serodiscordant couples (p= 0.0001). The combination of wild-type CCR2 and SDF1 genotypes (G/G + G/G) was higher among uninfected partners (80.48%) in HIV serodiscordant couples compared to the infected partners (60.97) (p= 0.005). Conclusion: HIV negative partner protection against HIV/AIDS infection may be attributed to the combination of wild-type genotypes (G/G and G/G) of CCR2 and SDF1 genes in HIV serodiscordant couples.

Background: Sexual minorities, such as men who have sex with men (MSM), are disproportionately impacted by HIV/AIDS compared to heterosexual men. The increased prevalence of HIV/AIDs among this group of individuals is associated with increased participation in HIV-related risk behavior, such as multiple sexual partnerships and injection drug use. However, very little is known about the prevalence of HIV and the risk behaviors related to HIV infection among MSM in Iran. This absence of data is due to the increased discrimination and stigmatization MSM, and other vulnerable populations face in Iran. This study was conducted to identify HIV-related risks, HIV prevalence and sociodemographic characteristics of the MSM population in Iran. Methods: A cross-sectional study was conducted among MSM attending the Sexual Health Clinic at Imam Khomeini Hospital in 2018. A sexual health screening questionnaire was used to aid in identifying HIV-related risk behaviors. HIV status was determined using an HIV rapid test and confirmed by an ELISA. Results: One hundred MSM enrolled in this study, out of which 41% were 18-25 years old. The majorities were single; almost one-third had a diploma degree. Only a fifth were employed, and about a quarter (25%) reported substance abuse. Among eighty-three people (83%) reported having sex during the past three months, and only 27 (27.3%) of participants always used condoms for sex. Among 80 participants tested for HIV, two positive results were detected (2.5%). Conclusion: Data collected through a sexual health questionnaire indicated that the prevalence of HIV is increased among MSM in Iran. This finding sheds light on the urgent need for the implementation of social programs providing counseling and healthcare to vulnerable populations in Iran.

Aims: To evaluate the frequency of the InSTIs mutations in a large cohort of HIV-infected people. Background: The Highly Active Anti-Retroviral Therapy (HAART) allows turning HIV infection from a fatal disease to chronic infection, and Integrase Strand Transfer Inhibitors (InSTIs) represent the cornerstone of this treatment. However, the spread of HIV-1 drug resistance mutations represents an emerging threat to the long-term success of HIV treatment programs. Objectives: To evaluate the trend of the HIV drug resistance to InSTIs in a large cohort of HIVpositive people in order to assess the risk represented by these subjects in the spread of the HIV infection to the community. Methods: A cross-sectional study was conducted analysing all the InSTIs resistance tests performed in HIV positive subjects during 2017-2019 by the HIV Laboratory of the University Hospital “Gaetano Martino” of Messina, Italy. Results: In 2017-2019, 252 InSTIs resistance tests were performed, with 59 (23.4%), 88 (34.9%), and 105 (41.7%) tests respectively in the three considered years. Overall, 28 (11.1%) samples showed resistance to at least one of the four InSTIs. We observed a significant percentage increase of 95% in the resistance to all four drugs. Conclusion: InSTI resistance is not rare. Therefore, continuous surveillance along with incessant health education and a wide offer of the HIV test, can be the most important tools in the fight against HIV infection.

Background: Injecting drugs is associated with a high risk of HIV infection, alongside the risk of a drug overdose and mental health problems. Objective: To evaluate the effect of methadone maintenance treatment (MMT) combined with rilpivirine (RPV)-based regimens on drug use of HIV individuals. Methods: This study was a prospective, open-label, controlled, drug-drug interaction trial at a single center for 24 weeks. Participants on stable MMT were randomly divided into two groups administered RPV/TDF/3TC (RPV group) and EFV/TDF/3TC (EFV group), respectively. Adjustment doses of methadone were monitored for 12 weeks. HIV-1 RNA was used to evaluate the effects of antiretroviral therapy at week 24. Acute opioid withdrawal-, drug craving questionnaire- and MOSHIV scales were used to assess study outcomes. Results: 22 and 18 cases of HIV-infected drug users were recruited in the RPV and EFV groups, respectively. Thirty-one cases had completed monitoring and clinical evaluation at week 24. In the RPV and EFV groups, 32% and 56% of the participants had methadone dose adjustment, respectively, indicating a significantly lower rate in the RPV group. The rates of individuals with HIV RNA levels from 50-500 copies/ml were 94% (RPV group) and 90% (EFV group). The drug craving questionnaire scale scores decreased in both groups. After one week of treatments, acute opioid withdrawal scale scores increased in both groups, with no significant difference between them. Conclusion: Concomitant administration of RPV does not significantly affect methadone and could decrease withdrawal symptoms. An RPV-based regimen may be used as first-line treatment in IDUs with HIV infection.

Background: The World Health Organization (WHO) announced the SARS-COV-2 disease pandemic on March 9, 2020. With the advent of this disease, another health burden was added to about 37.9 million people in the world who are infected with HIV and are suffering from various diseases. These people may be at serious risk of COVID-19. Information about the effects of COVID-19 on people living with HIV, is limited. Case Presentation: We reported a 61-year-old man who was a known case of HIV from 6 years ago that was being treated with HAART (highly active antiretroviral therapy). He also had a history of Hodgkin’s lymphoma from 4 years ago who underwent autologous bone marrow transplantation (BMT) 2 weeks before given referral to our hospital. He complained of weakness, anorexia, and fever. RT-PCR for SARS-COV-2-RNA was positive in his nasopharyngeal and oropharyngeal swab. He was diagnosed with COVID-19 infection and treated with atazanavir. After one week, the patient discharged in a good general state. Conclusion: To the best of our knowledge, it is the first report of COVID-19 infection in an HIV positive patient after BMT in Iran. Despite his immunodeficiency, COVID-19 disease had mild manifestations and he had a good prognosis. We hope that our report and that of others can remain promising to doctors and HIV patients cross fingers for COVID-19 recovery.