Predictors of severe hepatotoxicity among retroviral infected adults on HAART regimen in Ilubabor Zone, Southwest Ethiopia.

Nearly half of the deaths among hospitalized human immuno deficiency virus-infected patients in the highly active antiretroviral therapy era have been attributed to liver disease. This may range from an asymptomatic mild increase of liver enzymes to cirrhosis and liver failure. Different works of literature elucidated both retroviral infection and the adverse effects of highly active antiretroviral therapy as a cause of hepatotoxicity. Individual adaptations to medications and environmental exposures, shaped by cultural norms and genetic predispositions, could potentially modulate the risk and progression of liver disease in this population. Therefore, this study aims to assess the predictors of severe hepatotoxicity in retroviral-infected adults receiving highly active antiretroviral therapy regimens within the Ilubabor Zone, Southwest Ethiopia. A facility-based cross-sectional study was conducted among adult retroviral-infected patients in five selected anti-retro virus therapy clinics from May1 to July 30/2022. A systematic sampling technique was used to select 457 study participants and Binary logistic regression statistical data analysis was used, P value < 0.05 was considered statistically significant. The prevalence of severe hepatotoxicity was 21.44% in the study population. CD+4 count < 200 cells/mm3 (AOR = 2.19, 95% CI 1.04-5.22, P = 0.01), human immunodeficiency virus co-infection with tuberculosis (AOR = 2.82, 95% CI 1.01-8.29, P = 0.03) and human immuno deficiency virus co-infection with hepatitis-B/hepatitis C virus (AOR = 5.02, 95% CI 1.82-16.41) were predictors of severe hepatotoxicity. The magnitude of severe hepatotoxicity was high among adult retroviral-infected patients on highly active anti-retroviral drug regimens. Co-infection of human immuno deficiency virus with hepatitis B virus or hepatitis C virus, tuberculosis and CD4+T-cell count below 200 cells/mm3 were predictors of severe hepatotoxicity. Therefore, HIV patients on highly active antiretroviral therapy require close attention and regular monitoring of their liver function.

Highly active antiretroviral therapy-related effects on morphological connectivity in HIV.

OBJECTIVE: Suboptimal concentration of the antiretroviral drug is insufficient to inhibit HIV destruction on brain structure and function due to the resistance of blood brain barrier. We aimed to investigate highly active antiretroviral therapy (HAART)-related effects on the morphological connectivity in people with HIV (PWH). DESIGN: Case-control study. METHODS: Fifty-five HAART-treated for more than 3 months and 54 untreated PWH, as well as 66 demographically matched healthy controls underwent a high-resolution 3D T1-weighted MRI. Individual-level morphological brain network based on gray matter volume of 90 brain regions was constructed and network topological properties were analyzed. Network-based statistics (NBS) was performed to identify sub-networks showing significant differences in morphological connectivity. Correlation and mediation analyses were employed to evaluate associations between the morphological properties and clinical variables of PWH. RESULTS: Although PWH exhibited small-world architecture in their morphological brain networks, untreated PWH demonstrated altered network properties while HAART-treated PWH showed relatively similar network properties compared to healthy controls. Furthermore, HAART-related effects were mainly involved the bilateral putamen and left thalamus. The findings of NBS further indicated the cortico-striatum-thalamic-cortical loop was involved in the therapeutic-associated morphological network. The positive correlations between the HAART treatment and nodal degree and efficiency of the putamen were mediated by the number of CD4 + T lymphocytes. CONCLUSIONS: The topological properties are recovered to normal in PWH after HAART and the effects induced by HAART are mostly within the cortical-subcortical circuit.

Reasons, safety and efficacy analysis for conversion of HAART to TAF/FTC/BIC among HIV-infected patients.

BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION: The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.

Treatment success of rescue regimens after dual therapy failure in people living with HIV in a real-life setting.

OBJECTIVES: Few data on management of two-drug regimen (2DR) failure in people living with HIV (PLWH) are available. METHODS: Retrospective study of treatment-experienced PLWH on a 2DR who experienced virological failure (VF) [two consecutive viral loads (VLs) ≥50 copies/mL, single VL ≥1000 copies/mL, or antiretroviral therapy (ART) switch after single VL ≥50 copies/mL with previous blips] or discontinuation for toxicity (baseline). Integrase strand transfer inhibitor (INSTI)-based [one INSTI plus one nucleoside reverse transcriptase inhibitor (NRTI) (n = 78) or one non-NRTI (n = 20)] or boosted protease inhibitor (PI/b)-based [one PI/b plus one NRTI (n = 116) or one INSTI (n = 12)] 2DRs were included. Probabilities of treatment success (TS), VF and discontinuation for any other cause of rescue regimens were estimated by Kaplan-Meier curves. A stepwise Cox model was performed to assess predictors of TS. RESULTS: Overall, 226 PLWH were evaluated: at baseline, 144 individuals discontinued 2DR for toxicity and 82 had VF [median viraemia 81 (63-212) copies/mL]; 171 switched therapy (49.7% to triple regimen, 40.9% to different 2DR), while 55 (exclusively with VF) maintained failing regimens. Probabilities of 12- and 24-month TS were 75.6% and 64.7%, respectively. Higher TS probabilities were observed in individuals who switched ART at 2DR failure (P = 0.003) and PLWH who discontinued 2DR for toxicity (P = 0.008). Therapy switch was the only predictor of TS (P = 0.002). CONCLUSIONS: Overall probability of rescue regimens' TS introduced after 2DR failure is good. Prompt ART switch after 2DR failure is advisable.

Zinc improves sexual and erectile function in HAART-treated rats via the upregulation of erectogenic enzymes and maintenance of redox balance.

PURPOSE: HAART has been shown to impair sexual function and penile erection via perturbation of penile redox balance, while zinc has been established to exert antioxidant activity. Therefore, this study focused on the role and associated molecular mechanism of zinc in HAART-induced sexual and erectile dysfunction. MATERIALS AND METHODS: Twenty male Wistar rats were randomly grouped into four (n = 5 rats per group); the control, zinc-treated, HAART-treated, and HAART + zinc-treated groups. Treatments were per os daily for eight weeks. RESULTS: Zinc co-administration significantly improved HAART-induced increase in the latencies of mount, intromission, and ejaculations. Zinc also attenuated HAART-induced reduction in the motivation to mate, penile reflex/erection, and frequencies of mount, intromission, and ejaculations. In addition, zinc co-treatment improved HAART-induced decline in penile NO and cGMP, dopamine, and serum testosterone. More so, zinc prevented HAART-induced rise in penile activities of monoamine oxidase, acetylcholinesterase, phosphodiesterase-5, and arginase. Furthermore, concomitant treatment with zinc ameliorated HAART-induced penile oxidative stress and inflammation. CONCLUSION: In conclusion, our present findings show that zinc improves sexual and erectile function in HAART-treated rats by upregulating erectogenic enzymes via the maintenance of penile redox balance.

Cellular and molecular insights into incomplete immune recovery in HIV/AIDS patients.

Highly active antiretroviral therapy (ART) can effectively inhibit virus replication and restore immune function in most people living with human immunodeficiency virus (HIV). However, an important proportion of patients fail to achieve a satisfactory increase in CD4+ T cell counts. This state is called incomplete immune reconstitution or immunological nonresponse (INR). Patients with INR have an increased risk of clinical progression and higher rates of mortality. Despite widespread attention to INR, the precise mechanisms remain unclear. In this review, we will discuss the alterations in the quantity and quality of CD4+ T as well as multiple immunocytes, changes in soluble molecules and cytokines, and their relationship with INR, aimed to provide cellular and molecular insights into incomplete immune reconstitution.

Characteristics and evolution of cerebral aneurysms among adults living with HIV: A retrospective, longitudinal case series.

OBJECTIVE: Previous research indicates an increased risk of cerebral aneurysm formation in adults living with human immunodeficiency virus (ALWH), however there are few longitudinal studies on the risk factors for and outcomes of cerebral aneurysms in this population. We aim to describe the characteristics and evolution of cerebral aneurysms in a large cohort of ALWH. MATERIALS AND METHODS: A chart review was completed for all adults evaluated at an urban, safety-net U.S. hospital between January 1, 2000, and October 22, 2021, with history of both HIV and at least one cerebral aneurysm. RESULTS: A total of 82 cerebral aneurysms were identified amongst 50 patients (52% female sex). Forty-six percent of patients with a nadir CD4 count less than 200 cells/mm3 (N=13) and 44% of patients with maximum viral load >10,000 copies/mL (N=18) developed new aneurysms or were found to have aneurysm growth over time compared with 29% of patients with a CD4 nadir above 200 cells/mm3 (N=21) and 22% of patients with maximum viral load

Antiretroviral Treatment of HIV-2 Infection: Available Drugs, Resistance Pathways, and Promising New Compounds.

Currently, it is estimated that 1-2 million people worldwide are infected with HIV-2, accounting for 3-5% of the global burden of HIV. The course of HIV-2 infection is longer compared to HIV-1 infection, but without effective antiretroviral therapy (ART), a substantial proportion of infected patients will progress to AIDS and die. Antiretroviral drugs in clinical use were designed for HIV-1 and, unfortunately, some do not work as well, or do not work at all, for HIV-2. This is the case for non-nucleoside reverse transcriptase inhibitors (NNRTIs), the fusion inhibitor enfuvirtide (T-20), most protease inhibitors (PIs), the attachment inhibitor fostemsavir and most broadly neutralizing antibodies. Integrase inhibitors work well against HIV-2 and are included in first-line therapeutic regimens for HIV-2-infected patients. However, rapid emergence of drug resistance and cross-resistance within each drug class dramatically reduces second-line treatment options. New drugs are needed to treat infection with drug-resistant isolates. Here, we review the therapeutic armamentarium available to treat HIV-2-infected patients, as well as promising drugs in development. We also review HIV-2 drug resistance mutations and resistance pathways that develop in HIV-2-infected patients under treatment.

Incidence and risk factors of hypertriglyceridemia in males with human immunodeficiency virus who are treated with combination antiretroviral therapy: a retrospective cohort study.

BACKGROUND: Hypertriglyceridemia is associated with subclinical atherosclerosis and vascular inflammation even when low-density lipoprotein cholesterol levels are normal. However, few cohort studies on hypertriglyceridemia have been conducted in males with higher susceptibility to human immunodeficiency virus (HIV)-related deterioration of arterial structure and function. Our objective was to investigate the incidence of hypertriglyceridemia during treatment with combination antiretroviral therapy (cART) in males with HIV and explore its related risk factors. METHODS: In this retrospective study, we included 309 males living with HIV (median age 31 years [interquartile range 26-42.5]) who initiated cART treatment in our hospital from January 2013 to December 2018. We collected follow-up data on serum triglycerides and other related information as of June 31, 2021. A Cox proportional hazards regression model was used to analyze the related risk factors. RESULTS: In 666.7 person-years, hypertriglyceridemia occurred in 140 patients (triglyceride ≥2.3 mmol/L [200 mg/dL]), and the incidence rate was 21.0 per 100 person-years (Patients who took the lamivudine [3TC] + tenofovir disoproxil fumarate [TDF] + efavirenz [EFV] regimen accounted for 77.0% of the total patients.). Multiple Cox regression analysis showed that baseline CD4/CD8 ratio < 0.20 (hazard ratio [HR], 2.705 [95% confidence interval (CI): 1.381-5.296]; P = 0.004}, body mass index (BMI) ≥ 24.0 kg/m2 (HR, 1.768 [95% CI: 1.225-2.552]; P = 0.002), borderline high triglyceride at baseline (HR, 3.457 [95% CI: 2.162-5.527]; P < 0.001), and 3TC + zidovudine (AZT) + EFV regimen (HR, 2.702 [95% CI: 1.593-4.581]; P < 0.001), or 3TC + TDF + lopinavir/ritonavir (LPV/r) regimen (HR, 4.349 [95% CI: 2.664-7.102]; P < 0.001) were independent risk factors for hypertriglyceridemia. CONCLUSION: During the course of cART treatment, the incidence of hypertriglyceridemia in males with HIV was high. The main risk factors influencing its occurrence are a low baseline CD4/CD8 ratio, overweight and obesity, and the use of AZT or LPV/r in the cART regimen.

Perinatal outcomes associated with combination antiretroviral therapy compared with monotherapy.

OBJECTIVES: Increasing numbers of women living with HIV (WLHIV) worldwide receive combination antiretroviral therapy (cART) during pregnancy. We aimed to assess the risk of adverse perinatal outcomes in pregnant WLHIV receiving cART compared with pregnant WLHIV receiving zidovudine monotherapy. DESIGN: Systematic review and meta-analysis. METHODS: We searched four electronic literature databases (PubMed, CINAHL, Global Health, EMBASE) for studies published between 1 January 1980 and 20 April 2020 using a comprehensive search strategy. Studies reporting data on WLHIV receiving cART compared with WLHIV receiving monotherapy for 11 adverse perinatal outcomes were sought: preterm birth (PTB), very PTB, spontaneous PTB, low birthweight (LBW), very LBW, preterm and term LBW, small for gestational age (SGA), very SGA (VSGA), stillbirth, and neonatal death. Random-effects meta-analyses were conducted to calculate relative risk (RR) and 95% confidence intervals (95% CI). RESULTS: We included 30 studies reporting on 317 101 pregnant women in 27 countries. WLHIV receiving cART were at increased risk of PTB (RR 1.32, 95% CI 1.18-1.46), LBW (1.35, 1.19-1.53), SGA (1.32, 1.13-1.53), VSGA (1.64, 1.34-2.02), and stillbirth (2.41, 1.83-3.17) compared to WLHIV receiving monotherapy. The significance of these results was maintained in subgroup analyses for studies conducted in low and middle-income countries and average quality studies. Additionally, WLHIV receiving nonnucleoside reverse transcriptase inhibitor-based cART were associated with increased risk of PTB, LBW, and stillbirth, while WLHIV receiving protease inhibitor-based cART were associated with increased risk of PTB, compared with WLHIV receiving monotherapy. CONCLUSION: Pregnant WLHIV receiving cART are associated with increased risk of adverse perinatal outcomes, compared with WLHIV receiving monotherapy.

We should not stop considering HIV drug resistance testing at failure of first-line antiretroviral therapy.

HIV drug resistance is a major global hurdle to successful and sustained antiretroviral therapy. Global guidelines recommend testing for antiretroviral drug resistance and results are used to inform treatment regimen design for patients at different stages of therapy. Several clinical trials investigated optimal regimens after failure of first-line antiretroviral therapy, yielding data that advanced knowledge and informed care. However, further interpretation of data from these studies questioned the benefit of antiretroviral drug resistance testing for cases in which first-line treatment is not effective and, furthermore, that relying on the results of antiretroviral drug resistance testing could be misleading and unnecessary. In this Viewpoint, which is largely focused on high-income settings, we review these data, reflect on the potential problems with their interpretation, and call for caution in their extrapolation. Without negating the importance of the data, and recognising the varied circumstances related to HIV drug resistance testing in different global settings, we advise caution before changing current practice and recommendations. We believe that we should not universally stop considering HIV drug resistance testing at failure of first-line antiretroviral therapy.

Incidence of complications and revision surgery in HAART compliant HIV patients undergoing primary total hip and knee arthroplasty: an institutional review.

INTRODUCTION: Human immunodeficiency virus (HIV) positive patients are at high risk for osteonecrosis along with age-related osteoarthritis, resulting in a high number of joint reconstruction surgeries at younger ages in these immunosuppressed patients. Few previous studies have reported on patient outcomes in HAART (highly active antiretroviral therapy) compliant patients undergoing primary arthroplasty. The aim of this study is to report one institution's overall rate of complications and revision in HAART-compliant patients after primary hip and knee arthroplasty. METHODS: A retrospective chart review was performed spanning a 4 year period. This study included 50 primary joint arthroplasty patients diagnosed with HIV including 13 TKA (total knee arthroplasty) and 37 THA (total hip arthroplasty) with a prior diagnosis of HIV infection. Preoperative CD4 count and viral loads were recorded. Charts were reviewed for post-operative complications including infection and revision. RESULTS: The were a total of 11 postoperative complications (22%). There were 3 cases (6%) of soft tissue infection, 3 cases (6%) of implant loosening, 2 cases (4%) of dislocation, 1 case (2%) of lower extremity weakness, 1 case (2%) of venous thrombosis, and 1 case (2%) of arthrofibrosis. Of all patients, there were 6 cases of revision in this cohort (12%), 5 of which were aseptic etiology. All 3 infected patients had a history of IVDU. Two of these infected patients resolved with IV antibiotics while 1 underwent two-stage revision (2%). Patients that experienced post-operative complications had significantly elevated preoperative CD4 levels (983 versus 598, p = 0.003). CONCLUSION: Arthroplasty is a viable option for HAART-compliant patients. Most previous studies showing a higher risk for deep tissue infection and revision in HIV patients have not accounted for modern HAART. Our results show that compliance with HAART has vastly improved the outcomes of arthroplasty in these patients, while a history of IVDU is likely the largest risk factor for infection in this population.

Risk of Nonkeratinocyte Skin Cancers in People Living with HIV during the Era of Antiretroviral Therapy.

Antiretroviral therapy may alter susceptibility to nonkeratinocyte skin cancers (NKSCs) by improving immunity in people living with HIV. Using linked data from HIV and cancer registries in 12 states/regions in the United States during the antiretroviral therapy era (1996‒2018), we calculated standardized incidence ratios for 27 NKSCs, comparing incidence with that of the general population. Risk factors for NKSCs were evaluated using Poisson regression. There were 2,743 NKSCs diagnosed in 585,706 people living with HIV followed for 4,575,794 person-years. Kaposi sarcoma was the most common cancer (82%), followed by melanoma (12%) and cutaneous lymphoma (2.6%). Incidence was elevated for virus-related NKSCs: Kaposi sarcoma (standardized incidence ratio = 147, 95% confidence interval = 141‒153), diffuse large B-cell lymphoma (standardized incidence ratio = 5.19, 95% confidence interval = 3.13‒8.11), and Merkel cell carcinoma (standardized incidence ratio = 3.15, 95% confidence interval = 1.93‒4.87); elevated incidence for diffuse large B-cell lymphoma and Merkel cell carcinoma was observed only among people living with HIV with a previously acquired immunodeficiency syndrome diagnosis. Kaposi sarcoma risk was highest among men who have sex with men. Incidence was not increased for melanoma, adnexal carcinomas, and sarcomas. Melanoma and Merkel cell carcinoma arose disproportionately on sun-exposed skin, supporting a role for UVR in their development. In conclusion, risk for most NKSCs was similar to that of the general population during the antiretroviral therapy era, suggesting that people living with HIV without NKSC risk factors may not require intensive skin surveillance.

Peripheral sensory neuron CB2 cannabinoid receptors are necessary for both CB2-mediated antinociceptive efficacy and sparing of morphine tolerance in a mouse model of anti-retroviral toxic neuropathy.

Painful peripheral neuropathy is a common neurological complication associated with human immunodeficiency virus (HIV) infection and anti-retroviral therapy. We characterized the impact of two CB2 cannabinoid agonists (AM1710 and LY2828360 - ligands differing in signaling bias and CNS penetration) on neuropathic nociception induced by the antiretroviral agent Zalcitabine (2',3'-dideoxycytidine; ddC). We also used a conditional knockout approach to identify cell types mediating CB2 agonist-induced antinociceptive efficacy and sparing of morphine tolerance. AM1710 and LY2828360 alleviated ddC-induced neuropathic nociception in mice of both sexes. These benefits were absent in global CB2 knockout mice, which exhibited robust morphine antinociception. Like morphine, AM1710 blunted ddC-induced increases in proinflammatory cytokine (IL-1ß, TNF-α) and chemokine (CCL2) mRNA expression levels. We generated advillinCre/+;CB2f/f conditional knockout mice to ascertain the role of CB2 localized to primary sensory neurons in CB2-mediated therapeutic effects. Antinociceptive efficacy of both AM1710 and LY2828360, but not reference analgesics, were absent in advillinCre/+;CB2f/f mice, which exhibited robust ddC-induced neuropathy. In ddC-treated CB2f/f mice, LY2828360 suppressed development of morphine tolerance and reversed established morphine tolerance, albeit with greater efficacy in male compared to female mice. LY2828360 failed to block or reverse morphine tolerance in advillinCre/+;CB2f/f mice. The present studies indicate that CB2 activation may alleviate HIV-associated antiretroviral neuropathy and identify a previously unreported mechanism through which CB2 activation produces antinociceptive efficacy. Our results also provide the first evidence that a CB2 agonist can reverse established morphine tolerance and demonstrate that CB2 localized to peripheral sensory neurons mediates the opioid tolerance sparing efficacy of CB2 agonists.

Selenium and Omega-3 Fatty Acids Ameliorate Highly Active Anti-Retroviral Therapy (HAART)-induced Reproductive Impairment in Male Wistar Rats.

Highly active anti-retroviral therapy (HAART) is currently the main stay in the treatment of Human Immunodeficiency Virus (HIV) disease. This treatment regimen typically combines three or more antiretroviral drugs and like most drug combinations or polypharmacy, has side effects including those on reproductive function which could place HIV patients on HAART under double risk in terms of reproductive function. Part of tissue damage following HAART administration is blamed on oxidative stress. We therefore sought to explore effects of Omega 3 and Selenium, two common antioxidants on HAART-induced male reproductive impairment in a non-HIV animal model. Sixteen male adult Wistar rats weighing 120g to 250g used for the study were grouped into 4 groups of four rats each (control, HAART-only, HAART + Omega 3 and HAART + Selenium groups). Duration of daily administration was six weeks. Results showed no significant changes in pH of epidydimal semen among the groups. Sperm count and viability were significantly reduced in HAART-only compared with control (p<0.05) but increased in HAART + Omega 3 and HAART + Selenium groups compared with HAART-only group (p< 0.05). Sperm motility was significantly reduced in HAART-only compared with control group (p< 0.05). A significantly higher percentage of total sperm defects was observed in HAART-only group compared with control (p <0.05) but significantly lower in the HAART + Selenium compared with HAART-only groups (p<0.05). Serum testosterone was significantly reduced in HAART-only compared with control groups (p<0.05) but significantly increased in HAART + Omega 3 and HAART + Selenium groups compared with HAART- only group (p<0.05). Serum concentration of luteinizing and follicle stimulating hormones were not significantly different among the groups. Testicular concentration of malondialdehyde was significantly increased in HAART-only compared with control (p<0.05) but significantly reduced in HAART + Omega 3 and HAART + Selenium groups compared with HAART-only group (p<0.05 in each). Testicular glutathione peroxidase activity was significantly reduced in HAART-only and HAART + Selenium groups compared with control (p< 0.05), but significantly higher in HAART + Omega 3 and HAART + Selenium compared with HAART-only groups (p<0.05 each). Testicular superoxide dismutase activity was significantly lower in the HAART-only and HAART + Selenium compared with control (p<0.05) but significantly higher in HAART + Omega 3 and HAART + Selenium compared with HAART-only groups (p<0.05 each). Level of tumour necrosis factor - alpha in testes was significantly higher in HAART-only (p<0.05) but lower in the HAART + Selenium (p<0.05) groups compared with control. Tumor necrosis factor-alpha was however significantly reduced in HAART + Omega 3 and HAART + Selenium groups compared with HAART-only (p<0.05 each) groups. Interleukin-6 levels were significantly increased in all HAART-administered groups compared with control (p<0.05 each) though significantly reduced in HAART + Omega 3 and HAART + Selenium compared with HAART-only groups (p<0.05 each). In conclusion, co-administration of Omega 3 or Selenium with HAART ameliorates HAART-induced male reproductive impairment, alteration in redox and inflammatory status in rats. Keywords: HAART, male reproductive impairment, Omega 3, Selenium.

Impact of Protease Inhibitor-Based Highly Active Antiretroviral Therapy on Fetal Subcutaneous Fat Tissue in HIV-Pregnant Women in a Middle-Income Country.

BACKGROUND: HIV infection continues to be a global public health challenge, affecting approximately 1.7 million reproductive-aged women. Protease inhibitor-based highly active antiretroviral therapy (PI-HAART) has significantly reduced the risk of vertical transmission of HIV from mother to child. Nevertheless, concerns linger regarding the long-term effects, particularly on body composition, notably subcutaneous fat tissue (SFT). Although HIV-associated lipodystrophy syndrome (LS) has been well documented in adults and older children, its impact on fetuses exposed to PI-HAART remains underexplored. This study aims to evaluate SFT in the fetuses of HIV-pregnant women exposed to PI-HAART, assessing the potential clinical implications. METHODS: We conducted a comparative study between HIV-pregnant women receiving PI-HAART and an HIV-negative control group. Fetometry measurements were obtained via 3D ultrasound. SFT in the fetal arm and thigh segments was assessed. Data were analyzed using lineal multivariate regression and receiver-operating characteristics (ROC)-curve analysis. RESULTS: Fetuses exposed to PI-HAART exhibited a significant reduction in subcutaneous fat, particularly in the proximal third-middle union of the femur (coefficient: -2.588, p = 0.042). This reduction was correlated with lower newborn serum glucose levels (65.7 vs. 56.1, p = 0.007; coefficient: -1.277, p = 0.045). CONCLUSIONS: Our study sheds light on the connection between PI-HAART, fetal subcutaneous fat, and neonatal health. These findings might reveal the long-lasting effects of PI-HAART on newborns and children's well-being. Our results emphasize the need for a more balanced approach to managing pregnant women with HIV in developing countries and open new venues for research on the impact of intrauterine PI-HAART exposure on energy metabolism and fetal programming.

Prevalence of hearing loss among newly diagnosed highly active antiretroviral therapy (Haart) naive adult patients in port harcourt.

Background: Numerous studies have reported a relationship between human immune deficiency virus (HIV)/acquired immune deficiency virus (AIDS) and auditory functions. There is a dearth of information on the prevalence of hearing loss among newly diagnosed HAART naïve adult patients. Aim: This study therefore provides baseline information on the prevalence of hearing loss among newly diagnosed HAART naïve adult patients in Port Harcourt and serves as a reference for the role of HAART in HIV related hearing loss and for future studies. Patients and Methods: This is a prospective cross-sectional study involving 260 participants; 130 newly diagnosed and 130 HIV-negative controls aged 18 to 50 years from two centers in Port Harcourt from July, 2018 to January, 2019. Participants were clerked and diagnostic pure tone audiometry was done. Results: The rate of hearing loss was observed with Pure Tone Audiometry to be higher (P-value = 0.001) among newly diagnosed HAART naive adult patients 37 (28.5%) in comparison to the control 8 (6.2%). The mean age of all the study participants was 31.80 ± 9.61 years (study group 32.18 ± 10.18 years, control group 31.42 ± 9.12 years). Gender characteristic of participants also showed that males were 46 (35.4%) and females 84 (64.6%) giving a male, female ratio of 1:1.83 among newly diagnosed HAART naive adults, while among the control group there were males 49 (37.7%) and female 81 (62.3%) giving male: female ratio of 1:1.65. The rate of hearing loss at baseline was significantly (P = 0.001) higher among 37 HIV-positive HAART naïve patients (28.5%) compared with 8 control patients (6.2%). Conclusion: There was significant proportion of hearing loss among newly diagnosed HAART naive adult patients in Port Harcourt.