Current HIV Research - Volume 19, Issue 5, 2021

Background: Although the association between HIV infection and airways obstruction is well known, its etiopathogenesis is not clear. Objectives: Our aim was to analyze the association between biomarkers of systemic inflammation and bacterial translocation and pulmonary function tests in HIV infected patients and compare it between smokers and non-smokers. Methods: Cross-sectional, observational study. Inclusion criteria: people living with HIV with undetectable plasma viral load. Exclusion criteria: other comorbidities associated with systemic inflammation. Outcome variables: spirometry and diffusing capacity for carbon monoxide; explanatory variables: inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha), bacterial translocation (soluble CD14 [sCD14] and bacterial 16S rDNA), and variables related to HIV infection. Associations were tested using the Pearson/Spearman correlation tests, the student t test, and multivariable linear regression. Results: We included 71 patients (54.9% smokers). We did not observe significant differences in pulmonary function tests according to biomarkers of inflammation or bacterial translocation. In non-smokers (n=32), sCD14 was negatively correlated with forced expiratory volume in 1 second (R = -0.35, P = 0.048) and forced vital capacity (R= -0.40, P=0.023). Age, time since HIV diagnosis and CD4+ nadir were associated with alterations in PFTs. In smokers, the only association observed was between the pack-years and pulmonary obstruction. Conclusion: In non-smokers HIV patients, lung dysfunction can be, at least partially, related to bacterial translocation (sCD14), CD4+ nadir and time since HIV diagnosis.

Background: Hepatitis C virus (HCV) acts in the host as a complicated mixture of related variants with the potency to genetically escape host immune responses. Direct acting antivirals (DAAs) have been approved for HCV treatment with shorter duration, better cure rates and lower side effects. However, naturally occurring resistance associated substitutions (RASs) create some obstacles to this antiviral therapy success. Objective: In this study, we aimed at the determination of the naturally occurring NS3/4A RASs in HCV/human immunodeficiency virus (HIV)infected patients. Methods: A total of 120 DAA-naïve HCV-HIV co-infected patients were included. HCV NS3/4Agenome region was amplified with PCR and mutation analysis was performed by Sanger sequencing technique. The amino acid sequence diversity of the region was analyzed using geno2pheno HCV. Results: Phylogenetic analysis showed that 73 cases were infected by 3a and 47 subjects by subtype1a. The overall RASs among studied subjects were observed in 6 (5%) individuals from 120 studied cases who were infected with HCV 1a. V36M/L, Q80L, S122G/L, R155T/G, A156S, D168Y/N and S174A/N/T mutations were detected in this study. Conclusion: Although the prevalence of RASs was totally low in this study, the presence of several cases of double and triple mutants among this population suggests prior evaluation of protease inhibitors related mutations before initiation of standard treatment and also an investigation on a large population could be of high value.

Background: Despite the global decline in pediatric HIV infections, infants in sub-Saharan Africa still acquire HIV infection through inappropriate feeding. Objective: The objective of the study was to compare knowledge and predictors of infant feeding behavior between mothers living with HIV and controls of unknown HIV status in Gombe, northeast Nigeria. Methods: A cross-section of clinic-based samples of 84 HIV-positive mothers and 170 controls of unknown status were interviewed using validated questionnaires. Knowledge scores and self-reported infant feeding practices were analyzed. Multivariate logistic regression models were employed to determine predictors for infant feeding practices. Results: Transmission risk perception (95.2% vs. 65.3%) (p<0.05) and adequate knowledge of infant feeding (77.4% vs. 51.2%) (p<0.05) were higher among HIV-positive mothers than controls. Compared with mothers of unknown status (56.5%), a higher proportion of HIV-positive mothers (84.5%) reported breastfeeding the index infant exclusively for 6 months (p<0.05). In contrast, mixed feeding was more prevalent among controls (19.4% vs. 4.8%) (p<0.05). Further, over a third (39.3%) of HIV-positive mothers and 27.6% of controls weaned their infants at ≥12 months (p>0.05). Antenatal attendance, hospital delivery, knowledge, and positive attitude predicted infant feeding practices in both groups. The predictive roles of education and parity were limited to HIVpositive mothers, while the effects of maternal age and infant death were restricted to controls. Conclusion: Risk perception, knowledge, and exclusive breastfeeding rates were higher among mothers living with HIV. Antenatal care, hospital delivery, knowledge, and attitude predicted infant feeding practices in both groups. Girl child education, antenatal care, hospital delivery, and sustained promotion of exclusive breastfeeding with antiretroviral therapy are key to HIV-free infant survival.

Background: The “remission theory” is an emerging concept that suggests the presence of human immunodeficiency virus (HIV) results in decreased disease severity in patients with inflammatory bowel disease. This theory is based upon evidence that implicates CD4 T-lymphocytes in the pathogenesis of both Crohn’s disease and ulcerative colitis. This study sought to elucidate the legitimacy of this theory. Methods: A retrospective cohort analysis of all adult inpatient hospitalizations for inflammatory bowel disease (IBD) using the 2016 National Inpatient Sample (NIS) was conducted. Our study population included patients admitted with IBD who were infected with HIV. We compared our study group to patients who also had IBD but were not infected with HIV. Baseline demographic characteristics, resource utilization, and in-hospital mortality rates were extracted for both groups. Results: A total of 58,979 patients were admitted for IBD in 2016. Of those patients, we identified 145 who also had the presence of HIV. We found that patients with ulcerative colitis and HIV had a shorter length of hospital stay (4.1 vs. 5.9 days, p-value < 0.01), lower hospital charge ($35,716 vs $52,893, p-value < 0.01), and lower hospital cost ($7,814 vs. $13,395, p-value < 0.01) than those who did not have HIV. In patients with Crohn’s disease, the presence of HIV resulted in decreased colonoscopy rates (0% vs. 17.4%, p-value < 0.01); however, the rate of esophagogastroduodenoscopies was not statistically significant (7.1% vs. 14.7%, p-value 0.106). Conclusion: In this retrospective population-based study, we found that patients with ulcerative colitis and concurrent HIV had a milder course of the disease when compared to ulcerative colitis patients that were not infected with HIV. These findings support the remission theory in that HIV may play a role in inflammatory bowel disease.

Background: The intention of antiretroviral therapy (ART) and regular clinic visits are to engender safe sex attitudes among HIV-infected individuals. However, this may not be the case due to the perceived therapeutic benefits of ART and may result in exposure to drug-resistant HIV strains. Objectives: We aimed to determine the prevalence and predict the factors associated with risky sexual behaviors among ART users in a resource-limited environment. Methods: Two hundred and ninety-one sexually active ART-users aged 18-50 years and seeking care at the HIV clinic in Dodoma, Tanzania, participated in this study. The outcome variables modeled in a logistic regression were condom use, multiple sex partners, casual sex partners, and payment for sex. The predictors included in the models were the patients' socio-demographic characteristics. In addition, a new variable, sexual risk scores, was generated by culminating all the outcome variables. Finally, a multiple Poisson regression with the socio-demographic variables of the participants was used to model the sexual risk scores. Results: Patients reported inconsistent/no condom use (44%), payment for sex (4%), casual sex encounters (13%), multiple sex partners (21%), and STD symptoms (15%). While having a casual sexual partner was significantly associated with age group in a Pearson Chi-square (p=0.0147), participants ≤35 years old were less likely to have single-sex partners than older participants (AOR: 0.188, 95 C.I: 0.042-0.849). Meanwhile, the likelihood of condom use was higher among participants with no HIV-infected family members (AOR= 2.409, 95% C.I:1.236,4.697) and among participants who had single-sex partners (AOR= 2.721, 95% C.I.: 1.115,6.640); these participants were less likely to report STD symptoms (AOR=0.265, 95% C.I.: 0.081-0.865). Adjusted analysis showed that estimated mean sexual risk scores significantly increased (mean, λ=1.61, 95% C.I:1.0817-2.4063) for recent ART recipients (within 1-3 years vs. ≥8 years). However, sexual risk scores of participants with HIV stage 3 were 38.8% lower than participants at stage 4 (95% C.I.: 0.3910-0.9558), and non-alcohol drinkers had an adjusted mean sexual risk score of 29% lower than participants who were alcohol drinkers (95% C.I.: 0.5102-0.9879). Conclusion: Researchers should prioritize patients at HIV CTC for education concerning safe sexual practices for those characterized by alcohol consumption, younger age (less than 35 years old), HIV stage 4, or commencement of ART within three years.

Background: Bone alterations have been observed in the course of HIV infection, characterized by a marked decrease in bone mineral density (BMD) and an increase in the frequency of fractures as a result of fragility. We aim to evaluate early changes in bone metabolic profile and the possible association with tenofovir and other nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) in treatment-naïve HIV patients. Methods: We conducted a prospective study in naïve HIV-infected adults (under 50 years), separated into three groups according to NRTI therapy: tenofovir disoproxil fumarate (TDF); tenofovir alafenamide (TAF) and abacavir (ABC). BMD and epidemiological, immunological and metabolic bone parameters were evaluated. Bone markers were analyzed in plasma at baseline, 12 and 48 weeks after initiating treatment. Results: Average age of patients was 34.8 years (± 9.6). 92.4% of them with CD4 count > 200 cel/μL. At week 12 after starting treatment, both TDF [increase in PN1P (31.7%, p = 0.004), TRAP (11.1%, p = 0.003), OPN (19.3%, p = 0.045) and OC (38.6%, p = 0.001); decrease in OPG (-23.4%, p = 0.003)] and TAF [increase in 42.6% for CTX (p = 0.011), 27.3% for OC (p = 0.001) and 21% for TRAP (p = 0.008); decrease in OPG (-28.8%, p = 0.049)] presented a deep resorption profile compared to ABC, these differences in bone molecular markers, a tendency to equalize at week 48, where no significant differences were observed. Patients treated with TDF showed the greatest decrease in Z-score in both lumbar spine (LS) and femoral neck (FN) at week 48 without statistically significant differences. Conclusion: Treatment-naïve HIV patients have a high prevalence of low bone density. Treatment with TDF is associated with greater bone deterioration at 12 and 48 weeks. TAF seems to present similar early bone deterioration at 12 weeks which disappears at 48 weeks.

Background: Human immunodeficiency virus type 1 (HIV-1) is characterized by high genetic diversity due to its high mutation and recombination rates. Although, there is an increasing prevalence of Circulating Recombinant Forms (CRFs) worldwide, subtype B is still recognized as the predominant subtype in the Middle East and North Africa (MENA) region. There is a limited sampling of HIV in this region due to its low prevalence. The main purpose of this study is to provide a summary of the current status of the resident HIV subtypes and their distribution among Egyptian patients. Methodology: Forty-five HIV-1 patients were included in this study. Partial pol gene covering the protease (PR) and Reverse Transcriptase (RT) was successfully amplified in 21 HIV patients using nested PCR of cDNA of the viral genomic RNA, then sequenced. The sequence data were used for viral HIV-1 subtyping by 5 online subtyping tools: NCBI viral genotyping tool, Stanford University HIV database (HIVDB) subtyping program, REGA tool, Context-Based Modeling for Expeditious Typing (COMET) tool, and Recombinant Identification Program (RIP) tool. The final subtype assignment was based on molecular phylogenetic analysis. Results: Unexpectedly, non-B subtypes are dominating, with the most common circulating one is CRF02_AG (57.1%) followed by subtype B (14.3%), subtype BG recombinant (9.5%), CRF35_ AD (9.5%), subtype A1 and CRF06_cpx (4.8% each). Conclusion: To the best of our knowledge, this is the first study to tackle HIV-1 subtyping among the group of HIV-1 patients in Egypt. CRF02_AG is the most prevalent subtype in Egypt.

Background: Histoplasma capsulatum is an environmental fungus that causes opportunistic infections in AIDS patients in endemic areas but is uncommon in Europe. It shares clinical features with other opportunistic infections and lymphoproliferative disorders common in AIDS patients. The World Health Organization included Histoplasma antigen tests on the Lists of Essential In Vitro Diagnostics, however, they are not routinely available in non-endemic countries. Consequently, mycoses can be a great challenge for clinicians in non-endemic countries. Case Presentation: We report the case of a 42-year-old Colombian woman admitted to an Italian university hospital with diarrhea, acute renal failure, psychomotor impairment and fever. When a screening HIV test came back positive, she was screened for opportunistic infections with no results. Given the severity of her clinical condition a broad spectrum antibacterial and antifungal therapy was started in addition to HAART. A blood smear documented leucocytes inclusions, identified as capsular structures. On suspicion of Histoplasma capsulatum the patient was started on empiric amphotericin B. The diagnosis was confirmed by positive serology. Despite therapy, the patient died shortly after. In the following days, the mycology laboratory managed to grow Histoplasma capsulatum, thus confirming the diagnosis of invasive histoplasmosis in AIDS. Conclusion: The case highlights the need for a high index of suspicion for the diagnosis of endemic mycosis outside of endemic areas, and the necessity of expanding access to tests. Even if antigen/ antibody tests are not available, however, blood smear has worldwide feasibility and allows a rapid diagnosis.

Background: Adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome (CS) with right adrenal adenoma combined with HIV infection has rarely been reported. Case presentation: A 39-year-old Chinese male patient with HIV infection was admitted to our hospital due to increased blood pressure in the previous 2 years and weight gain in the previous 6 months. Endocrinological examinations showed that blood cortisol (8 a.m.) was 22.23 μg/dl, the level of ACTH (8 a.m.) was less than 1pg/ml and twenty-four-hour urinary cortisol was 1429 μg/24h. ACTH-independent CS was diagnosed based on low ACTH levels (<1.00 pg/ml), a lack of cortisol circadian rhythms, and unsuppressed cortisol levels by dexamethasone. The ultrasonography and multislice spiral computed tomography scan revealed a right adrenal mass. Due to the HIV status of the patient, we measured the count of CD4+ T helper cells. Laparoscopic right adrenal resection was performed after the CD4+ T helper cell count was > 200 cells/μl. Subsequent immunohistochemical staining confirmed right adrenal adenoma. Results: The postoperative recovery was good, and wound healing was possible. After surgical treatment, endocrinological examinations indicated that the level of ACTH increased and the levels of serum cortisol and twenty-four-hour urinary cortisol decreased, which indicated that CS was controlled. CD4/CD8 was 0.47 at reexamination, and the patient's immunity was improved. Conclusion: Due to the potential side effects of steroid drugs, clinicians should use these medications with caution and closely monitor the development of adrenal deficiency.