Is renal dysfunction amplified in an arginine vasopressin induced rat model of preeclampsia?

Renal dysfunction is important in preeclampsia (PE) pathophysiology and has not been fully explored in the arginine vasopressin (AVP) rat model of PE. This study aimed to determine kidney toxicity associated with this model. Female Sprague Dawley rats (n = 24) were subcutaneously infused with AVP or saline for 18 days. Urine samples (GD8, 14 and 18) were used to determine the levels of albumin, VEGF-A, clusterin, NGAL/Lipocalin-2, KIM-1, cystatin C, TIMP-1, ß2M and OPN via Multiplex ELISAs. Albumin, and NGAL/lipocalin-2 were significantly elevated in the PAVP vs PS group on GD14 and GD18 (p < 0.001) respectively. VEGF-A significantly decreased in the pregnant vs non-pregnant groups on GD14 and 18 (p < 0.001). Clusterin (p < 0.001) and OPN (p < 0.05) were significantly higher in the PAVP vs PS group on GD18. Cystatin C and KIM-1 are significantly upregulated in the PAVP vs PS groups throughout gestation (p < 0.05). ß2M is significantly elevated in the PAVP vs PS group on GD14 and 18 (p < 0.05). AVP elevated the urinary levels of the kidney injury biomarkers and replicated the renal dysfunction associated with PE development. Our findings confirm the potential applications of this model in studying the mechanisms underlying renal damage in PE.

Management of Polycystic Ovarian Syndrome: A Qualitative Inquiry among Complementary and Alternative Medicine Practitioners in South Africa.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a complex reproductive endocrinopathy affecting 4-20% of females of reproductive age. PCOS and its consequent complications such as infertility, diabetes mellitus and cardiovascular disease significantly impact clinical management. Complementary and alternative medicine (CAM), including homeopathy, is gaining recognition in PCOS management. There remains a paucity of formal protocols for managing PCOS within homeopathy and other CAM systems. AIMS/OBJECTIVES: This study aimed to explore and document existing therapeutic practices in the management of PCOS from diagnosis to treatment used by practitioners within various disciplines of CAM: viz., homeopathy, ayurveda, unani tibb, traditional Chinese medicine (TCM) and naturopathy, in the context of their unique philosophical background. METHODS: In this explorative, descriptive study, data were collected from CAM practitioners in eThekwini Municipality, KwaZulu Natal, South Africa, using semi-structured interviews and analysed using Tesch's and Creswell's methods for qualitative analysis. RESULTS: Four themes emerged from the data, namely: CAM philosophical perspectives on PCOS, contributing factors, diagnosis of PCOS, and management of PCOS. Five sub-themes emerged: clinical diagnosis of PCOS, CAM-specific characterisation of PCOS, CAM-specific treatment of PCOS, adjunctive therapies, and lifestyle interventions. Homeopathic management comprised several prescribing methods, the most common ones being miasmatic/constitutional, keynote and clinical, alongside adjunctive therapies and lifestyle interventions. Other CAM modalities adopted similar holistic approaches. CONCLUSIONS: This paper offers a comprehensive exploration of the perceptions, clinical investigations and management practices in PCOS by homeopaths and four other CAM modalities - ayurveda, unani tibb, TCM and naturopathy - as documented in the study. Homeopaths and other CAM practitioners employed CAM-specific therapies, along with adjunctive therapies and lifestyle interventions, adopting holistic approaches. Enhancing the quality of life through emotional counselling, stress reduction and lifestyle improvements emerged as shared objectives across modalities. Our findings underscore the need to further explore inter-disciplinary collaboration in PCOS management among registered CAM practitioners, with the potential to expand the scope of comprehensive care for PCOS patients.

Hesperidin improves physiological outcomes in an arginine vasopressin rat model of pre-eclampsia.

BACKGROUND: Hesperidin, a flavanone commonly found in citrus fruits and herbal formulations, has emerged as a potential new therapeutic agent for modulating several diseases. Since pre-eclampsia is a growing public health threat, it may negatively impact the economy and increase the disease burden of South Africa. Phytocompounds are easily accessible, demonstrate minimal side effects, and may confer novel medicinal options as a treatment and preventive preference. OBJECTIVE: To investigate the physiological, biochemical, and hematological outcomes of hesperidin in an arginine vasopressin (AVP)-induced rodent model of pre-eclampsia. METHODS: Female Sprague-Dawley rats were surgically implanted with mini-osmotic pumps to deliver AVP (200 ng/h) subcutaneously. Animals were treated with hesperidin at 200 mg/kg.b.w via oral gavage for 14 days. Systolic and diastolic blood pressures were measured on GD 7, 14, and 18 using a non-invasive tail-cuff method and were euthanized on GD 21. RESULTS: The findings showed that hesperidin administration significantly decreased blood pressure (P < 0.05) and urinary protein levels in pregnant rats (P < 0.001). Placental and individual pup weight also increased significantly in the pregnant hesperidin-treated groups compared to AVP untreated groups (P < 0.001). Biochemical and hematological markers such as white blood cell count and lymphocyte levels differed significantly (P < 0.05) in AVP groups treated with and without hesperidin. CONCLUSION: Our results suggest that hesperidin is an antihypertensive agent with modes of action associated with its diuretic and blood pressure lowering effects and reduction of proteinuria in AVP-induced pre-eclamptic rats.

Socioeconomic determinants of risky sexual behaviors and HIV seropositivity among university students in South Africa: A case control analysis.

Socioeconomic determinants of risky sexual behaviors in sub-Saharan Africa are well known. The socioeconomic determinants of the sexual behaviors of university students, however, remain unclear. This case control study aimed to investigate the socioeconomic determinants of risky sexual behavior and HIV seropositivity among university students in KwaZulu-Natal (KZN), South Africa. Participants (N = 500; 375 HIV uninfected and 125 HIV infected) from four public higher educational institutions in KZN were recruited, using a non-randomized strategy. Socioeconomic status was assessed by food insecurity, access to the government loan scheme, and sharing of the bursary/loan with family. The findings of this study suggest that students reporting food insecurity were 1.87 times more likely to have multiple sexual partners; 3.18 times more likely to engage in transactional sex for money; and presented a fivefold higher risk of engaging in transactional sex for basic needs other than money. Accessing the government financing for education and sharing of the bursary/loan with family was also significantly associated with an increased risk of having an HIV seropositive status. A significant association between socioeconomic measures, risky sexual behavior, and HIV seropositivity is demonstrated in this study. Moreover, the socioeconomic risks and drivers when determining and/or developing HIV prevention interventions, including preexposure prophylaxis use, should be considered by healthcare providers based at campus health clinics.

The Clinical Value of Rodent Models in Understanding Preeclampsia Development and Progression.

PURPOSE OF REVIEW: Preeclampsia (PE) is a leading global cause of maternal and fetal morbidity and mortality. The heterogeneity of this disorder contributes to its elusive etiology. Due to the ethical constraints surrounding human studies, animal models provide a suitable alternative for investigation into PE pathogenesis and novel therapeutic strategies. The purpose of this review is to compare and contrast the various rodent models used to study PE, in order to demonstrate their value in investigating and identifying different characteristics of this disorder. RECENT FINDINGS: Several approaches have been employed to create an appropriate animal model of PE, including surgical, genetic manipulation, and pharmacological methods in an attempt to mimic the maternal syndrome. Despite the absence of a model to completely model PE, these models have provided valuable information concerning various aspects of PE pathogenesis and novel therapeutic strategies and have led to the discovery of potential predictive markers of PE. Rodent and murine models have contributed significantly to the study of the pathology associated with specific aspects of the disorder. As a single fully encompassing animal model of PE remains absent, the use of a combination of models has potential value in understanding its etiology as well as in new treatment and management strategies.

Kidney injury molecule-1 and podocalyxin dysregulation in an arginine vasopressin induced rodent model of preeclampsia.

OBJECTIVE: To assess renal injury in an arginine vasopressin (AVP) rodent model of preeclampsia. STUDY DESIGN: Urinary expression of kidney injury molecule-1 (KIM-1), urinary protein and creatinine was determined in rodents (n = 24; pregnant AVP, pregnant saline, non-pregnant AVP and non-pregnant saline), which received a continuous dose of either AVP or saline via subcutaneous mini osmotic pumps for 18 days, using a Multiplex kidney toxicity immunoassay. Renal morphology was assessed using haematoxylin and eosin staining and transmission electron microscopy. The immunolocalization of KIM-1 and podocalyxin was qualitatively evaluated using immunohistochemistry. RESULTS: Urinary KIM-1 and urinary protein levels were significantly increased in treated vs. untreated rats on gestational days 8 (p < 0.05), 14 (p < 0.001) and 18 (p < 0.001). The pregnant rats displayed a lower trend of creatinine compared to the non-pregnant groups, albeit non-significantly. KIM-1 was immunolocalized in the proximal convoluted tubules in AVP treated vs. untreated groups. In contrast, podocalyxin was weakly immunostained within glomeruli of pregnant AVP treated vs. pregnant untreated rats. Histological evaluation revealed reduced Bowman's space, with some tubular and blood vessel necrosis in the pregnant treated group. Ultrastructural observations included effacement and fusion of podocyte foot processes, glomerular basement membrane abnormalities, podocyte nuclear crenations, mitochondrial oedema and cristae degeneration with cytoplasmic lysis within treated tissue. CONCLUSION: Our findings demonstrate region-specific kidney injury particularly glomerular impairment and endothelial injury in AVP-treated rats. The findings highlight the utility of this model in studying the mechanisms driving renal damage in a rodent model of preeclampsia.

Placental Morphology and Morphometry: Is It a Prerequisite for Future Pathological Investigations?

Successful pregnancy is dependent on implantation, nutrient and gas exchange, as well as fetal protection from the immunologic attack. Placental pathologies and preterm delivery closely correlate with the size and shape of the placenta. Additionally, normal vaginal microbiota is disturbed during viral insults such as SARS-CoV-2 and HIV, with consequent placental anomalies. This chapter focuses on placental development, morphology, and pathology while also investigating placental bed structure and function. Placental anomalies with regard to HIV-1 and SARS-CoV-2 infection and placental morphometric image analysis and its relevance for verification of placental pathology are explored. Since image analysis remains optional for routine diagnostic purposes, authentication of placental appraisal warrants the use of measurable predefined definitions. Immunohistochemical analyses of placental morphology and angiogenic, epithelial, and apoptotic mechanisms facilitate research into etiopathogenetic pathways involved in placental anomalies with a focus on discovering novel diagnostic foci. Thus, image analyses as an adjunct to complement pathological investigations are recommended.

Unravelling the Mechanistic Role of ACE2 and TMPRSS2 in Hypertension: A Risk Factor for COVID-19.

BACKGROUND: This review explores the mechanistic action of angiotensin-converting enzyme- 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in the renin-angiotensinaldosterone system (RAAS) that predisposes hypertensive patients to the adverse outcome of severe COVID-19. METHODS AND RESULTS: Entry of SARS-CoV-2 into the host cell via ACE2 disrupts the RAAS system, creating an imbalance between ACE and ACE2, with an increased inflammatory response, leading to hypertension (HTN), pulmonary vasoconstriction and acute respiratory distress. SARSCoV- 2 may also predispose infected individuals with existing HTN to a greater risk of severe COVID-19 complications. In the duality of COVID-19 and HTN, the imbalance of ACE and ACE2 results in an elevation of AngII and a decrease in Ang (1-7), a hyperinflammatory response and endothelial dysfunction. Endothelial dysfunction is the main factor predisposing hypertensive patients to severe COVID-19 and vice-versa. CONCLUSION: Despite the increase in ACE2 expression in hypertensive SARS-CoV-2 infected patients, ARBs/ACE inhibitors do not influence their severity and clinical outcomes, implicating continued usage. Future large-scale clinical trials are warranted to further elucidate the association between HTN and SARS-CoV-2 infection and the use of ARBs/ACEIs in SARS-CoV-2 hypertensive patients.

Does HAART dysregulate angiogenesis in HIV infected preeclampsia?

A dysregulation of angiogenic mediators has been implicated in HIV infection. Inconsistent data exists on highly active antiretroviral therapy (HAART) usage in pregnancy and its association with PE development. In view of the high prevalence of HIV infection and PE in SA, this study was aimed at determining PlGF and sFlt-1 levels in HIV-infected normotensive and preeclamptic pregnancies treated with HAART. Both PlGF and sFlt-1 were quantified in serum from HIV positive [normotensive (N+) and preeclamptic (P+)]; and HIV negative [normotensive (N-) and preeclamptic (P-)] pregnancies, using a Milliplex Multiplex immunoassay. sFlt-1 was significantly upregulated in P+ vs the N+ groups. PlGF was significantly downregulated in PE vs normotensive groups, regardless of HIV status. sFlt-1/PlGF ratio was significantly increased in PE- vs the N- groups. We report an amplification of sFlt-1 in lieu of PlGF down-regulation in HIV-infected pregnancies receiving HAART .

Circulating levels of transforming growth factor beta-1, 2 and 3 in HIV associated preeclamptic pregnancies.

The active role of transforming growth factor-beta in implantation, embryonic development and decidualization has driven our interest to evaluate circulating TGF-ß(1-3) in the synergy of HIV associated pregnancy. Serum TGF-ß(1-3) was quantified in normotensive (n = 38) and preeclamptic (n = 38) pregnant women, who were stratified by HIV status, HIV negative (n = 19) and HIV positive (n = 19), using a Bioplex immunoassay.Based on HIV status, we report no significant difference in TGF-ß-1 (p = .95) and TGF-ß2 (p = .80) however, TGF-ß3 was significantly downregulated in HIV positive (p = .03) vs the HIV negative groups. A significant positive correlation (p < .05) was noted between TGF-ß3 and gestational age (p = .03) (r = 0.51), birth weight (p = .04) (r = 0.53) and CD4 count (p = .02) (r = 0.53). Bivariate correlation between isoforms based on HIV status showed several significant positive associations. In the synergy of HIV infected PE, we demonstrate an association between TGF-ß(1-3) with PE emanating from the hypoxic microenvironment that affects receptor-SMAD activity. Decreased TGF-ß3 levels in HIV infected PE, may originate from ARV usage and/or the mutational/physiological dysregulation of SMAD expression. Impact StatementWhat is already known on this subject? TGF-ß overexpression can convert its protective functions into pathogenic variants. It has a significant role in the oxidatively stressed and inflammatory condition of tissue fibrosis and hence may also be dysregulated in the microenvironment of PE. In HIV infection, TGF-ß promotes viral replication and spreading through the induction of cellular proteins which induce TGF-ß production. Also, mononuclear phagocytes infected with HIV also produce increased TGF-ß mRNA and proteins.What do the results of the study add? Our results show no association of TGF-ß isoforms (1-3) based on pregnancy type (PE vs normotensive pregnant) at term. The lack of association may be linked to TGF-ßs dual promoter/suppresser nature or to gestational age.What are the implications of these findings for clinical practice and/or further research? Large-scale comprehensive clinical trials are warranted to elucidate the association and mechanistic role of TGF-ß receptor-SMAD signalling, the effect of its inhibitors on cell invasion and angiogenesis as well as to deliver valuable data for the detection of novel therapeutic agents in pregnancies complicated by HIV infection.

Mating success of timed pregnancies in Sprague Dawley rats: Considerations for execution.

This study compares three different mating techniques in Sprague-Dawley rats, using the pregnancy rate as the main indicator of success. It provides recommendations for timed-pregnancy experiments to achieve an appropriate sample size for the study of human pregnancy disorders. The implementation of a preconditioning phase, determination of the estrous cycle, the use of two mating strategies (Lee-Boot and Whitten effect), female: male mating ratios, and cohabitation duration should be considered as they improve the mating success rate.

Normative scores for select neuropsychological battery tests for the detection of HIV-associated neurocognitive disorder amongst Nigerians.

Background: The study aimed to derive socio-demographic-corrected norms for selecting neuropsychological (NP) battery tests for people living with HIV (PLWHIV) in Nigeria. This cross-sectional study was conducted amongst patients who attended the general outpatient clinic and junior staff of the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla. Aims and Objectives: To determine the normative scores for select neuropsychological battery test for the detection of neurocognitive disorder amongst Nigerians PLWHIV. A sample of 92 individuals received voluntary HIV testing. Methods: Eligibility criteria were being HIV negative, aged 18-64 years and formal education. We undertook a brief neuromedical examination to identify putative exclusion criteria. We sampled four NP tests covering seven cognitive domains and the motor speed component of the International HIV Dementia Scale (IHDS-MS). We presented the normative scores using statistics of mean, median, standard deviation (SD), kurtosis and skewness. Results: All the participants were Nigerians aged 18-64 years. Most (74.1%) of the participants were females. The mean and median ages of the participants were 42.6 ± 11.42 years and 44 years, respectively. The effect of gender on NP performance was limited to the digit span test (DST)-forwards, while education affected all expect IHDS-MS and DST-backwards. The cut-off scores for defining mild and severe impairment varied (moving from 1SD to 2SD) for all cognitive domains except for IHDS-MS and DST. Conclusions: With these preliminary normative scores, it will be easier to identify and classify the severity of neurocognitive impairment amongst PLWHIV in Nigeria, thus facilitating the goal of keeping HIV-associated dementia to a minimum. The lack of variability in the IHDS-MS and DST is unfavourable.

Aerobic exercise for HIV-associated neurocognitive disorders in individuals on antiretroviral therapy: A randomised controlled trial.

INTRODUCTION: The increasing burden of self-limiting forms of HIV-associated neurocognitive disorder (HAND) in the antiretroviral therapy era calls for adjunctive interventions. The study aimed to determine the effects of a 12-week aerobic exercise programme on HAND. METHODS: This is a parallel-group, randomized controlled trial with concealed allocation and intention-to-treat analysis. This study was a clinic-based programme. Seventy-three patients with HAND were enrolled in the trial. The intervention comprised a moderate-intensity aerobic exercise, 20-60 min per session, three times per week, for twelve weeks. The control group received exercise education. Prevalence of HAND constituted the primary outcome. HAND was identified and classified following the Frascati criteria. We computed the odds ratio and number needed-to-treat to estimate the treatment effect. RESULTS: There were 73 patients (38 in exercise and 35 in control arm). Individuals in the exercise arm recorded a significantly higher reduction in working memory deficit (OR = 5.14; CI = 2.6-10.4; NNT = 6) but not in attention-deficit (OR = 0.31, CI = 0.2-0.5; NNT = -5) compared to the control group at twelve-week. Reductions in attention deficit (OR = 1.55, 95 CI = 1.0-2.4; NNT = 5) and HAND prevalence (OR = 1.8, 95 CI = 1.2-2.8); NNT = 8) were significantly higher in the exercise group compared the control group at three-month. No significant between-group difference in functional independence was observed immediately after exercise (p > 0.05). DISCUSSION: The neuroprotective effects of aerobic exercise appear selective and vary with cognitive abilities impaired and aerobic capacity, with a greater change occurring with improved aerobic capacity. CONCLUSION: Individuals with working memory and attention deficits may benefit more from moderate-intensity aerobic exercise.

Correction: Aerobic Exercise in HIV-Associated Neurocognitive Disorders: Protocol for a Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/29230.].

South African medicinal plants displaying angiotensin-converting enzyme inhibition: Potential use in the management of preeclampsia.

In resource-limited settings, such as South Africa, hypertensive disorders of pregnancy such as preeclampsia, is the most common direct cause of maternal deaths. Current management strategies of preeclampsia primarily involve the use of pharmaceutical drugs, which are frequently associated with undesirable side-effects. Moreover, these drugs are often not easily accessible due to financial and economic constraints. Consequently, many patients rely on traditional medicine obtained from medicinal plants to manage health-related conditions. Angiotensin-converting enzyme inhibitors are widely used drugs for the management of preeclampsia. This narrative review aims to highlight the use of indigenous medicinal plants from South Africa with Angiotensin-converting enzyme inhibitory activity whilst also evaluating their potential use in the treatment of hypertension in pregnancy. This information will influence traditional healers and sangomas in their patient management. Furthermore, the antihypertensive potential of these plants will be unraveled thus facilitating the development of new naturally occurring pharmaceutical products to reduce maternal and neonatal mortality and morbidity.

Effects of aerobic exercise on quality of life of people with HIV-associated neurocognitive disorder on antiretroviral therapy: a randomised controlled trial.

BACKGROUND: HIV-associated neurocognitive disorder (HAND) negatively impacts quality of life (QoL) of people living with HIV who are on antiretroviral therapy (ART). Behavioural intervention adjunct to ART may improve QoL of people with HAND. We determine the effect of a 12-week aerobic exercise programme on QoL in people with HAND who were receiving ART. TRIAL DESIGN: This was a parallel-group, randomised controlled trial with concealed allocation and intention-to-treat analysis. METHODS: We identified 73 participants diagnosed with HAND. Participants were sampled from an earlier study that examined the prevalence of HAND according to the Frascati criteria. Participants were randomised and allocated to an intervention of 12-weeks of aerobic exercise, comprising three 20-60 min sessions per week of moderate-intensity aerobic exercise using a cycle ergometer. The primary outcome was QoL, which was evaluated using the World Health Quality of Life Questionnaire (WHOQoL)-BREF. RESULTS: Participants in the exercise (n = 39) and control (n = 35) groups had similar sociodemographic characteristics (p > 0.05). Following the 12-week aerobic exercise programme, participants in the exercise group had improved physical (p < 0.001), psychological (p = 0.008) and environmental (p = 0.001) domains of the QoL (p = 0.001) and overall QoL (p = 0.001) relative to the control group. Similarly, participants in the exercise group had lower depression scores than participants in the control group. Depression scores in the exercise group were still lower 3 months post-intervention (p = 0.007). Only the improvements in physical (p = 0.02) and psychological (p = 0.007) domains of QoL were sustained at 3 months post-intervention. CONCLUSIONS: Aerobic exercise improves the QoL of people with HAND. To ensure sustained benefits, people with HAND may need to engage in long-term physical exercise. Trial registration The trial is registered with the PAN African Trial Registry (PACTR). Date: 01/09/2020, ID: PACTR202009483415745.

Impact of HIV-associated cognitive impairment on functional independence, frailty and quality of life in the modern era: a meta-analysis.

HIV-associated neurocognitive disorder (HAND) is an important sequela of HIV infection. Combined antiretroviral therapy (cART) has improved the health outcomes of many people living with HIV but has given rise to a less severe but limiting form of HAND. The study aimed to evaluate the impact of HAND on medication adherence, activities of daily living (ADL), quality of life and frailty. This systematic review adheres to the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We searched MEDLINE, PubMed, CINAHL, Academic Search Complete, and PsycINFO online databases. Studies were included if they examined the relationship between HAND and medication adherence, ADL, quality of life and frailty, and were conducted between 1997 and 2021. We used a random-effects meta-analysis model to assess the impact of HAND on outcome variables. Forty papers, totaling 11,540 participants, were included in the narrative and quantitative syntheses. Cognitive impairment was associated with poorer medication adherence (r = 0.601, CI 0.338 to 0.776, p = 0.001, I2 = 94.66). Cognitive impairment did not influence ADL (r = 0.167, CI-0.215 to 0.505, p = 0.393) and quality of life (r = 0.244, CI 0.117 to 0.548, p = 0.182). In the cART era, HAND appears to be associated with adherence to medication, which may influence future health outcomes. In PLWHIV who are adherent to cART, cognitive impairment does not appear to interfere with ADL and quality of life.

Aerobic Exercise in HIV-Associated Neurocognitive Disorders: Protocol for a Randomized Controlled Trial.

BACKGROUND: Since the introduction of antiretroviral therapy (ART), the incidence of HIV-associated dementia has drastically fallen. Despite using ART, people living with HIV continue to experience less severe but limiting forms of HIV-associated neurocognitive disorder (HAND). People living with HIV who are on ART and experiencing symptoms of HAND may benefit from aerobic exercise. OBJECTIVE: This protocol describes a randomized controlled trial designed to determine the effects of a 12-week aerobic exercise program on HAND in Southeastern Nigeria. METHODS: At least 68 patients diagnosed with HAND will be randomly placed into either an aerobic exercise group or control group. Patients in the aerobic exercise group will perform a moderate intensity workout on a stationary bicycle ergometer, 3 times a week for 12 weeks. We will measure the primary outcomes including neurocognitive performance, prevalence of HAND, viral load, and CD4 count. We will evaluate postexercise neurocognitive performance using reliable neuropsychological tests relevant to people living with HIV, in line with the Frascati criteria. We will assess secondary outcomes such as quality of life, activity limitation, and social participation using the World Health Organization Quality of Life (WHOQOL)-Brief, and the Oxford Participation and Activities questionnaire. We will use exploratory statistics to test the data for normality and homogeneity. We will analyze the effect of the exercise program on HAND using relative risk (RR) and absolute risk reduction (number needed to treat). Analysis of covariance will be run to estimate the effect of exercise on quality of life and activity and participation level. RESULTS: This funded trial was approved by the Institutional Review Board in May 2020. The protocol was approved on June 15, 2020. Enrollment commenced in January 2021 and was completed in May 2021. Over 60% of the participants were recruited at the time of first submission to JMIR Mental Health. Data curation is still ongoing; hence, data analysis is yet to be executed. Study outcomes are expected to be published in March 2022. CONCLUSIONS: This is a protocol for a randomized controlled trial that aims to evaluate the effect of a 12-week aerobic exercise program on HAND in Southeastern Nigeria. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR202009483415745; https://tinyurl.com/2p97zpu9. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/29230.