Sex differences in hypertension among people living with HIV after initiation of antiretroviral therapy.

Background: Hypertension is common in people living with HIV (PLWH) on antiretroviral therapy (ART). In the general population and in experimental animal models, the incidence of hypertension is greater in males than in females, especially during the premenopausal period. However, it is not known whether there are sex differences in hypertension associated with HIV and ART, and the factors contributing to incident hypertension among PLWH have not been well characterized. In this study, we aimed to determine the time course, sex differences and factors associated with incident hypertension in PLWH initiating ART. Methods and results: We conducted a retrospective study in which we used programmatic data from the ART registry to identify sex differences in the determinants of incident hypertension among PLWH initiating the ART regimen from Livingstone University Teaching Hospital in Zambia and followed for 8 years. Males developed hypertension earlier, 2 years after initiating ART, compared to 6 years in females. In multivariable analysis, increasing age, baseline systolic blood pressure and baseline mean arterial pressure (MAP) were associated with increased risk for developing incident hypertension. Also, participants who switched to the integrase strand transfer inhibitor, dolutegravir (DTG) or the protease inhibitor, lopinavir boosted with ritonavir were 2 and 3 times more likely to develop hypertension when compared to those on non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, these relationships were abrogated by sex, as self-reported male sex was the major contributor in predicting incident hypertension. While none of the factors remained significantly associated with incident hypertension upon multivariate analysis among females, body mass index (BMI), and use of protease inhibitors remained strongly associated with hypertension among males. Conclusion: Our results indicate that the use of protease inhibitors and BMI are important predictors of incident hypertension among males. Thus, blood pressure and BMI should be closely monitored, particularly in males living with HIV on protease inhibitors. In addition, identifying specific factors that protect females from developing hypertension early is important but remains to be determined.

Immediate pressor response to oral salt and its assessment in the clinic: a time series clinical trial.

BACKGROUND: High blood pressure (BP) is associated with high-salt consumption especially in sub-Saharan Africa. Although the pressor effect of salt is viewed as a chronic effect, some studies suggest that a salty meal may increase BP immediately in some individuals, and that this effect may cause endothelial dysfunction. Therefore, the aim of our research was to study the immediate pressor response to oral salt (IPROS) and its determinants, with the expectation that a simple methodology may be devised to diagnose it in the clinic or in low-resource environments. METHODS: We conducted a time series trial at Livingstone Central Hospital. We present data in 127 normotensive participants who ingested 2 g of sodium chloride; their BP was monitored for 120 minutes in intervals of 10 minutes. Sociodemographic and clinical data were collected. Descriptive and inferential statistics were used for analyses of data. RESULTS: Median age was 30 years (interquartile range, 22-46 years) and 52% were female patients. An increase of ≥10 mmHg in mean arterial pressure (MAP), considered a clinically significant IPROS, was present in 62% of participants. Systolic BP 30 minutes after the salt load was a significant predictor of IPROS, avoiding the need to calculate MAP in the clinic setting. CONCLUSIONS: We confirm the presence of an IPROS in a high proportion (62%) of otherwise normotensive participants. The average time course for this response was 30 minutes and its duration was sustained for the 120-minutes period of study in most of the participants. Prediction of IPROS by ∆SBP (change in systolic blood pressure) at 30 minutes allows for easy assessment of possible responder status in the clinic. Our data indicate that the IPROS to oral salt-loads in the range currently consumed by the Western world and African populations in single meals may increase the 24-hour BP load, which is a risk factor for hypertension and target organ damage. The relevance of our findings indicates the need to include dietary sodium assessment in the diagnosis, prevention, and management of high BP.

Antimicrobial resistance of Neisseria gonorrhoeae isolated from patients attending sexually transmitted infection clinics in Urban Hospitals, Lusaka, Zambia.

BACKGROUND: Neisseria gonorrhoeae, the causative agent for sexually transmitted infection (STI) gonorrhoea, has emerged with a significant public health impact on acquiring resistance to antimicrobials available for treatment. The resistance of N. gonorrhoeae limit treatment options and contributed to high morbidity associated with gonorrhoea. Data on antimicrobial resistance (AMR) profiles in N. gonorrhoeae is scares in Zambia. This study aimed to determine the antibiotic susceptibilities in N. gonorrhoeae isolates from Lusaka, Zambia. METHODS: A prospective cross-sectional study was conducted on 630 STI patients who presented with urethral or vaginal discharge from 2019 to 2020. Urethral and endocervical secretions were cultured on Modified Thayer Martin agar and incubated at 36 °C ± 1 °C in 5% CO2 for 24 h. Identification of N. gonorrhoeae isolates was achieved by Gram stain, oxidase, nitrocefin disk, BactiCard Neisseria, and Viteck® Compact. The AMR profiles were determined using E-test. Statistical significant was determined by Pearson's Chi-square test, Mann-Whitney U test, or logistic regression with p-values of < 0.05 indicating significance. RESULTS: A total of 630 patients were recruited of which 46% (290/630) with the median of 29 years and interquartile range (IQR) of 19-39 years were male. The median of the females was 26 years and IQR of 15-37 years. Neisseria gonorrhoeae was isolated from 19.4% (122/630) patients of which 72.9% (89/122) were male, with highest prevalence of isolation in the age category of 25-34 years. The prevalence of resistance was high to penicillin (85.2%), tetracycline (68.9%) and ciprofloxacin (59.8%) with MIC90 of 32 µg/mL, 8 µg/mL, and 8 µg/mL respectively. The isolates had reduced susceptibility to cefixime (1.6%), spectinomycin (4.9%) and (4.9%) for azithromycin. All isolates were susceptible to ceftriaxone. Risk factors associated with AMR were douching in females (AOR 6.69, 95% CI; 1.11-40.31, p = 0.039), female gender (AOR 7.64, 95% CI; 1.11-52.33, p = 0.048), HIV-positivity (AOR 26.59, 95% CI; 3.67-192.7, p = 0.005), no condom use or unprotected sex (AOR 5.48, 95% CI; 1.17-22.75 p = 0.026), sex trading (AOR 4.19, 95% CI; 1.55-11.33, p = 0.010), and over-counter treatment of ciprofloxacin (AOR 3.44, 95% CI; 1.17-22.75, p = 0.023). CONCLUSION: The N. gonorrhoeae resistance to penicillin, tetracycline and ciprofloxacin was high necessitating revision of the treatment guidelines. However, no resistance to ceftriaxone was detected. Therefore, monitoring of antibiotic resistance remains critical in Zambia.

Correlates of hypertension among persons living with HIV at Livingstone Central Hospital: A cross sectional study

Background: Persons living with HIV (PLWH) are more likely to develop hypertension and cardiovascular disease than the HIV-negative population. The new hypertension guidelines by the American Heart Association (AHA) and the American College of Cardiology (ACC) lowered the definition of hypertension from systolic and diastolic blood pressure (BP) of ≥ 140/90mmHg to ≥ 130/80, respectively. This study was aimed at determining the prevalence and factors associated with hypertension in PLWH in Livingstone using the new hypertension diagnostic criteria. Methods: This was a cross-sectional study. We recruited 226 antiretroviral treated PLWH attending routine visits. Socio-demographic, health and clinical data including BP readings were collected. Interviewer-structured questionnaires adapted from the World Health Organization Stepwise approach to Surveillance ( WHO STEPs) and the international physical activity questionnaire (IPAQ) were used to collect data. Statistical evaluations were employed to elucidate relationships between hypertension and all response variables. Results: The prevalence of hypertension using the old and new guidelines was 16% and 42%, respectively. Factors significantly associated with increased and reduced odds of developing hypertension after adjustments in multivariate logistic regression were age, body mass index (BMI), employment status, fasting blood sugar (FBS) and table salt consumption, respectively (p<0.05 for all). Using the new AHA/ACC criteria for hypertension shifted the prevalence from 16% (old criteria) to 42%.Conclusion: The prevalence of hypertension in PLH in Livingstone was 42% and the major risk factors associated with hypertension in PLWH were increasing age, BMI and FBS. We recommend the inclusion of FBS in routine measurements in PLWH. The AHA/ ACC new guidelines should be reenforced in low-cost settings to increase the treatment of hypertension among PLWH.

Spectrum of common Hodgkin lymphoma and non-Hodgkin lymphomas subtypes in Zambia: a 3-year records review.

BACKGROUND: Lymphomas usually present with different occurrence patterns across different geographical locations, but their epidemiology in Zambia is yet to be extensively explored. OBJECTIVES: To study the spectrum of lymphoma subtypes prevalent within the Zambian population. METHODS: Histopathological records with suspected lymphoma at the University Teaching Hospital (UTH) in Lusaka from the year 2014 to 2016, diagnosed based on the 2008 World Health Organization (WHO) criteria were reviewed. The analysis was done in terms of type, sex, age, and site of biopsy; and Fisher's exact test was used for significance testing. RESULTS: During the study period (2014-2016), there were more B cell neoplasms {222 (92.5%)} than T cell neoplasms {18 (7.5%)}. Non-Hodgkin's lymphoma (NHL) was seen in 191 (79.6%) whereas classic Hodgkin's lymphoma (CHL) was seen in 39 (16.3%). Burkitt's lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) showed equal proportions {17.5% of all lymphoma cases (42/240) each}, as the most prevalent subtypes of NHL whereas marginal zone B cell lymphoma was the rarest subtype with 1.4% (4/240). For CHL, mixed cellularity and lymphocyte rich subtypes (4.6% of all lymphoma cases) were the most common subtypes. There was a statistically significant difference in the occurrences of lymphoma subtypes across different age categories (p = 0.002). CONCLUSION: Zambia has a diverse lymphoma subtypes population, affecting a relatively young population. The data from this study will serve as a baseline for improved health care provision and more robust future studies.

HIV-positive demonstrate more salt sensitivity and nocturnal non-dipping blood pressure than HIV-negative individuals.

BACKGROUND: High dietary salt and a lack of reduced blood pressure (BP) at night (non-dipping) are risk factors for the development of hypertension which may result in end-organ damage and death. The effect of high dietary salt on BP in black people of sub-Saharan Africa living with HIV is not well established. The goal of this study was to explore the associations between salt sensitivity and nocturnal blood pressure dipping according to HIV and hypertension status in a cohort of adult Zambian population. METHODS: We conducted an interventional study among 43 HIV-positive and 42 HIV-negative adults matched for age and sex. Study participants were instructed to consume a low (4 g) dietary salt intake for a week followed by high (9 g) dietary salt intake for a week. Salt resistance and salt sensitivity were defined by a mean arterial pressure difference of ≤5 mmHg and ≥ 8 mmHg, respectively, between the last day of low and high dietary salt intervention. Nocturnal dipping was defined as a 10-15% decrease in night-time blood pressure measured with an ambulatory blood pressure monitor. RESULTS: The median age was 40 years for both the HIV-positive and the HIV-negative group with 1:1 male to female ratio. HIV positive individuals with hypertension exhibited a higher BP sensitivity to salt (95%) and non-dipping BP (86%) prevalence compared with the HIV negative hypertensive (71 and 67%), HIV positive (10 and 24%) and HIV-negative normotensive (29 and 52%) groups, respectively (p < 0.05). Salt sensitivity was associated with non-dipping BP and hypertension in both the HIV-positive and HIV-negative groups even after adjustment in multivariate logistic regression (< 0.001). CONCLUSIONS: The results of the present study suggest that high dietary salt intake raises blood pressure and worsens nocturnal BP dipping to a greater extent in hypertensive than normotensive individuals and that hypertensive individuals have higher dietary salt intake than their normotensive counterparts. Regarding HIV status, BP of HIV-positive hypertensive patients may be more sensitive to salt intake and demonstrate more non-dipping pattern compared to HIV-negative hypertensive group. However, further studies with a larger sample size are required to validate this.

Hypertension and Metabolic Syndrome in Persons with HIV.

PURPOSE OF REVIEW: With the advent of highly active antiretroviral therapy (ART), the life span of persons with HIV (PWH) has been nearly normalized. With aging, prevalence of the metabolic syndrome (MetS), including hypertension, has increased in the HIV population and exceeds that in the general population in some studies. This is due to a combination of traditional risk factors in addition to the effects attributable to the virus and ART. We review recent findings on the mechanisms contributing to MetS and hypertension in PWH, particularly those specific to the viral infection and to ART. RECENT FINDINGS: Activation of the renin-angiotensin-aldosterone system (RAAS) and chronic immune activation contribute to the development of MetS and hypertension in PWH. HIV proteins and some ART agents alter adipocyte health contributing to dyslipidemias, weight gain, and insulin resistance. HIV infection also contributes to hypertension by direct effects on the RAAS that intertwine with inflammation by the RAAS also contributing to T cell activation. Recent data suggest that in addition to current ART, therapeutic targeting of the MetS and hypertension in PWH, by interfering with the RAAS, treating insulin resistance directly or by use of immunomodulators that dampen inflammation, may be critical for preventing or treating these risk factors and to improve overall cardiovascular complications in the HIV-infected aging population.

Elevated Eosinophils as a Feature of Inflammation Associated With Hypertension in Virally Suppressed People Living With HIV.

Background People living with HIV (PLWH) are at increased risk of cardiovascular disease, including hypertension, which persists despite effective plasma viral suppression on antiretroviral therapy. HIV infection is characterized by long-term alterations in immune function, but the contribution of immune factors to hypertension in PLWH is not fully understood. Prior studies have found that both innate and adaptive immune cell activation contributes to hypertension. Methods and Results We hypothesized that chronic inflammation may contribute to hypertension in PLWH. To test this hypothesis, we enrolled a cohort of 70 PLWH (44% hypertensive) on a long-term single antiretroviral therapy regimen for broad phenotyping of inflammation biomarkers. We found that hypertensive PLWH had higher levels of inflammatory cytokines, including tumor necrosis factor-α receptor 1, interleukin-6, interleukin-17, interleukin-5, intercellular adhesion molecule 1 and macrophage inflammatory protein-1α. After adjustment for age, sex, and fat mass index, the circulating eosinophils remained significantly associated with hypertension. On the basis of these results, we assessed the relationship of eosinophils and hypertension in 2 cohorts of 50 and 81 039 similar HIV-negative people; although eosinophil count was associated with prevalent hypertension, this relationship was abrogated by body mass index. Conclusions These findings may represent a unique linkage between immune status and cardiovascular physiological characteristics in HIV infection, which should be evaluated further.

HIV, immune activation and salt-sensitive hypertension (HISH): a research proposal.

OBJECTIVE: The objective of this study is to quantify and compare the effect of excess dietary salt on immune cell activation and blood pressure in HIV versus HIV negative individuals. RESULTS: Salt-sensitivity is associated with increased immune cell activation in animal studies. This concept has not been tested in people living with HIV. This study will therefore add more information in elucidating the interaction between HIV infection and/or anti-retroviral therapy (ART), immune-activation/inflammation and hypertension.

Patho-immune Mechanisms of Hypertension in HIV: a Systematic and Thematic Review.

PURPOSE OF REVIEW: To systematically review recent findings on the role of immune cell activation in the pathogenesis of hypertension in people living with HIV (PLWH) and compare studies from Sub-Saharan Africa with what is reported in the USA and European literature according to guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RECENT FINDINGS: PLWH have an increased risk for development of hypertension and cardiovascular disease. Chronic immune activation contributes to hypertension but the inflammatory milieu that predisposes PLWH to hypertension is poorly understood. We identified 45 relevant studies from 13 unique African countries. The prevalence of hypertension in PLWH on antiretroviral therapy (ART) and the ART-naive PLWH ranged from 6 to 50% and 2 to 41%, respectively. Interleukin (IL)-17A, interferon (IFN)-γ, and higher CD4+ T cell counts were associated with hypertension in ART-treated participants. Targeting adaptive immune activation could provide improved care for hypertensive PLWH. Further research is needed to characterize the inflammatory milieu contributing to hypertension in PLWH especially in African populations where the global burden of HIV is the highest.

Magnetic resonance spectroscopy to assess neuroinflammation and neuropathic pain.

Proton magnetic resonance spectroscopy ((1)H MRS) has been applied to numerous clinical studies, especially for neurological disorders. This technique can non-invasively evaluate brain metabolites and neurochemicals in selected brain regions and is particularly useful for assessing neuroinflammatory disorders. Neurometabolites assessed with MRS include the neuronal markers N-acetylaspartate (NAA) and glutamate (Glu), as well as the glial marker myo-inositol (MI). Therefore, the concentrations of these metabolites typically correspond to disease severity and often correlate well with clinical variables in the various brain disorders. Neuroinflammation with activated astrocytes and microglia in brain disorders are often associated with elevated MI, and to a lesser extent elevated total creatine (tCr) and choline containing compounds (Cho), which are found in higher concentrations in glia than neurons, while neuronal injury is indicated by lower than normal levels of NAA and Glu. This review summarizes the neurometabolite abnormalities found in MRS studies performed in patients with neuroinflammatory disorders or neuropathic pain, which also may be associated with neuroinflammation. These brain disorders include multiple sclerosis, neuroviral infections (including Human Immunodeficiency virus and Hepatitis C), degenerative brain disorders (including Alzheimer's disease and Parkinson's disease), stimulant abuse (including methamphetamine and cocaine) as well as several chronic pain syndromes.

Characteristics of Activated Monocyte Phenotype Support R5-Tropic Human Immunodeficiency Virus.

BACKGROUND: Microbial translocation has been recognized as an important factor in monocyte activation and contributing to AIDS pathogenesis with elevated plasma lipopolysaccharide (LPS) levels, as a marker for microbial translocation, seen in advanced HIV disease. Therefore, the current study was undertaken to assess monocyte activation in vitro by LPS and to determine its impact on monocyte phenotype. METHODS: Monocytes from non-HIV-infected donors were analyzed for CD14, CD16, CD69, TNFα, and CCR5 by flow cytometry pre- and post-stimulation with LPS. In-vitro cultures were then set up to expose non-activated and activated monocytes to R5-, X4-, and dual (R5/X4)-tropic viruses; and the amount of HIV present on the cells was assayed. RESULTS: Non-HIV-infected monocytes, after LPS stimulation, were confirmed to have an activated phenotype with increase in CD16 and CD69 surface expressions (p<0.05). The activation phenotype was supported by increase in TNFα production, p<0.05. The activated monocytes had increased surface CCR5 (from 21% to 98%; p=0.05); and were found to have more R5-tropic virus than non-activated monocytes (p<0.05). CONCLUSIONS: Following activation by LPS, non-HIV-infected monocytes were found to have increase in surface CCR5. These activated monocytes, when exposed to R5-tropic virus, were found to have more virus compared to non-activated monocytes. The significance of the findings could lie in explaining how microbial translocation plays a role in HIV progression; and possibly promoting CCR5-directed strategies in treating HIV.