Brief Report: Changes in Nocturnal Heart Rate Variability in People Living With HIV During the First Year of Antiretroviral Therapy Compared With HIV-Uninfected Community Controls.

BACKGROUND: Higher nocturnal heart rate and lower nocturnal heart rate variability (HRV) is associated with increased cardiovascular disease mortality. Longitudinal studies on nocturnal HRV in people living with HIV (PLWH) are lacking. METHODS: We conducted a 1-year prospective cohort study of adult PLWH and HIV-uninfected community controls in northwestern Tanzania. At enrollment, we collected data on cardiovascular risk factors and tested blood samples for hemoglobin, insulin, CD4 cell count, and C-reactive protein. We measured nocturnal HRV and heart rate at baseline and first-year follow-up. Mixed effect linear regression was used to determine predictors of lower HRV. RESULTS: Of the 111 enrolled participants (74 PLWH and 37 HIV-uninfected adults), 57.7% were female and the median age was 40 years. Over 1 year of follow-up, the average nocturnal heart rate was 4.5 beats/minute higher in PLWH ( P = 0.006). In the fully adjusted model (with age, sex, nocturnal heart rate, and diabetes), average nocturnal HRV was 10.5 milliseconds lower in PLWH compared with HIV-uninfected adults ( P = 0.03). Unlike with nocturnal heart rate, nocturnal HRV did not improve after 1 year of ART in PLWH or HIV-uninfected adults (fully adjusted change = -2.5 milliseconds, P = 0.45). Lower educational attainment, lesser pancreatic ß-cell function, and anemia were associated with higher HRV. CONCLUSIONS: Nocturnal parasympathetic nervous system function was persistently lower in PLWH compared with HIV-uninfected adults even after antiretroviral therapy initiation. Improving nocturnal autonomic nervous system function could be a target for cardiovascular disease prevention in PLWH.

Perceptions, facilitators and barriers of physical activity among people living with HIV: a qualitative study.

BACKGROUND: People living with HIV (PLWH) have low levels of physical activity. Using the social ecological model to understand perceptions, facilitators and barriers of physical activity in this population is of importance for developing contextualised interventions to improve physical activity in PLWH. METHOD: This was a qualitative sub-study conducted between august and November 2019 as part of a cohort study on diabetes and associated complications in HIV infected in Mwanza, Tanzania. Sixteen in-depth interviews and three focus groups with nine participants in each were conducted. The interviews and focus groups were audio recorded, transcribed and translated into English. The social ecological model was considered during the coding and interpretation of the results. Transcripts were discussed, coded and analyzed using deductive content analysis. RESULTS: Forty-three PLWH aged 23-61 years participated in this study. The findings showed that most PLWH perceived physical activity as beneficial to their health. However, their perceptions of physical activity were rooted within existing gender stereotypes and roles in the community. Running and playing football were perceived as activities for men while household chores activities were for women. Further, men were perceived to do more physical activity than women. For women, household chores and income-generating activities were perceived as sufficient physical activity. Social support and engagement of family members and friends in physical activity were reported as facilitators of physical activity. Reported barriers of physical activity were lack of time, money, availability of physical activity facilities and social support groups, and poor information on physical activity from health care providers in HIV clinics. Human-immunodeficiency virus (HIV) HIV infection was not perceived by PLWH as a barrier for doing physical activity but most family members did not support them to do physical activity, fearing that it might worsen their condition. CONCLUSION: The findings demonstrated differing perceptions, facilitators and barriers of physical activity among PLWH. Interventions addressing awareness, gender stereotypes and roles related to physical activity from individual to community level are needed. Supportive environment and infrastructures are needed to improve physical activity levels in PLWH in Tanzania.

The association of physical activity and cardiorespiratory fitness with ß-cell dysfunction, insulin resistance, and diabetes among adults in north-western Tanzania: A cross-sectional study.

Introduction: Research on the associations of physical activity and cardiorespiratory fitness with ß-cell dysfunction and insulin resistance among adults in Sub-Saharan Africa (SSA) is limited. We assessed the association of physical activity and cardiorespiratory fitness with ß-cell function, insulin resistance and diabetes among people living with HIV (PLWH) ART-naïve and HIV-uninfected Tanzanian adults. Method: In a cross-sectional study, we collected data on socio-demography, anthropometry, fat mass and fat free mass and C-reactive protein. Data on glucose and insulin collected during an oral glucose tolerance test were used to assess ß-cell dysfunction (defined as insulinogenic index <0.71 (mU/L)/(mmol/L), HOMA-ß index <38.3 (mU/L)/(mmol/L), and overall insulin release index <33.3 (mU/L)/(mmol/L)), oral disposition index <0.16 (mU/L)/(mg/dL)(mU/L)-1, insulin resistance (HOMA-IR index >1.9 (mU/L)/(mmol/L) and Matsuda index <7.2 (mU/L)/(mmol/L), prediabetes and diabetes which were the dependent variables. Physical activity energy expenditure (PAEE), sleeping heart rate (SHR), and maximum uptake of oxygen during exercise (VO2 max) were the independent variables and were assessed using a combined heart rate and accelerometer monitor. Logistic regressions were used to assess the associations. Results: Of 391 participants, 272 were PLWH and 119 HIV-uninfected. The mean age was 39 ( ± 10.5) years and 60% (n=235) were females. Compared to lower tertile, middle tertile of PAEE was associated with lower odds of abnormal insulinogenic index (OR=0.48, 95%CI: 0.27, 0.82). A 5 kj/kg/day increment of PAEE was associated with lower odds of abnormal HOMA-IR (OR=0.91, 95%CI: 0.84, 0.98), and reduced risk of pre-diabetes (RRR=0.98, 95%CI: 0.96, 0.99) and diabetes (RRR=0.92, 95%CI: 0.88, 0.96). An increment of 5 beats per min of SHR was associated with higher risk of diabetes (RRR=1.06, 95%CI: 1.01, 1.11). An increase of 5 mLO2/kg/min of VO2 max was associated with lower risk of pre-diabetes (RRR=0.91, 95%CI: 0.86, 0.97), but not diabetes. HIV status did not modify any of these associations (interaction, p>0.05). Conclusion: Among Tanzanian adults PLWH and HIV-uninfected individuals, low physical activity was associated with ß-cell dysfunction, insulin resistance and diabetes. Research is needed to assess if physical activity interventions can improve ß-cell function and insulin sensitivity to reduce risk of diabetes and delay progression of diabetes in SSA.

Blood Pressure and Body Composition During First Year of Antiretroviral Therapy in People With HIV Compared With HIV-Uninfected Community Controls.

BACKGROUND: Body composition changes may explain the rapid increase in blood pressure (BP) in people with HIV (PWH) during the first year of antiretroviral therapy. METHODS: We analyzed data from a cohort of PWH and HIV-uninfected adults from the same communities in Mwanza, Tanzania. Blood pressure (BP, mm Hg) and body composition data were collected at baseline and 12-month follow-up. We used multivariable linear regression to compare BP changes in PWH and HIV-uninfected adults, and the relationship between changes in body composition and changes in BP. RESULTS: BP data were available for 640 PWH and 299 HIV-uninfected adults. Sixty-four percent were women and the mean age was 38 years. In PWH, systolic BP (SBP) increased (114-118) whereas SBP decreased (125-123) in HIV-uninfected participants. Fat mass increased by 1.6 kg on average in PWH and was strongly associated with the change in BP (P < 0.001). The greater increase in SBP in PWH was partly explained by the lower baseline SBP but PWH still experienced a 2.2 (95% CI: 0.3-4.2) greater increase in SBP after adjustment. Weight gain partially mediated the relationship between HIV and SBP increase in PWH; a 1-kg increase in fat mass accounted for 0.8 (95% CI: 0.6-1.1) increase in SBP. CONCLUSIONS: Weight and fat mass increase rapidly in PWH during the first 12 months of antiretroviral therapy and contribute to a rapid increase in SBP. Interventions to prevent excessive increase in fat mass are needed for PWH.

Association of sickle cell trait with ß-cell dysfunction and physical activity in adults living with and without HIV in Tanzania.

This study aimed to investigate sickle cell trait (SCT) associations with physical activity, markers of insulin secretion and resistance, and glucose among people living with HIV infection (PLWH), both antiretroviral therapy (ART) naive and experienced, and HIV-uninfected adults. This was a cross-sectional study conducted in Mwanza, Northwestern Tanzania. We used data of 668 participants attained from two sub-studies of CICADA study. Mean age was 40 (SD 11.5) years, 402 (61.7%) were females and 157 (24.1%) had SCT. PLWH were 422 (64.7%), of these, 80 (18.9%) were on ART. People with SCT had higher risk of having an isolated ß-cell dysfunction compared to those without SCT (RRR = 1.82, CI: 1.10, 3.01, p = 0.02). People with SCT but without HIV infection had lower average acceleration on the trunk longitudinal axis (ACCx) and higher level of self-reported physical activity. 30 min oral glucose tolerance test among PLWH on ART was higher in those with SCT compared to those without SCT. People with SCT are at higher risk of having ß-cell dysfunction and those with SCT on ART are at more risk of developing diabetes. Future studies to investigate the interaction between SCT and HIV/ART on risk of diabetes should be considered.

Levels and correlates of physical activity and capacity among HIV-infected compared to HIV-uninfected individuals.

INTRODUCTION: In the HIV-infected individuals, physical activity improves physical strength, quality of life and reduces the risk of developing non-communicable diseases. In Sub-Saharan Africa, HIV-infected patients report being less active compared to HIV-uninfected individuals. We assessed the levels and correlates of objectively measured physical activity and capacity among HIV-infected antiretroviral therapy (ART)-naive individuals compared to HIV-uninfected individuals in Mwanza, Tanzania. METHOD: We conducted a cross-sectional study among newly diagnosed HIV-infected ART-naive individuals and HIV-uninfected individuals frequency-matched for age and sex. Socio-demographic data, anthropometrics, CD4 counts, haemoglobin level, and C-reactive protein (CRP) were collected. Physical activity energy expenditure (PAEE) was assessed as measure of physical activity whereas sleeping heart rate (SHR) and grip strength were assessed as measures of physical capacity. Multivariable linear regression was used to assess the correlates associated with physical activity and capacity. RESULTS: A total of 272 HIV-infected and 119 HIV-uninfected individuals, mean age 39 years and 60% women participated in the study. Compared to HIV-uninfected individuals, HIV-infected had poorer physical activity and capacity: lower PAEE (-7.3 kj/kg/day, 95% CI: -11.2, -3.3), elevated SHR (7.7 beats/min, 95%CI: 10.1, 5.3) and reduced grip strength (-4.7 kg, 95%CI: -6.8, -2.8). In HIV-infected individuals, low body mass index, moderate-severe anaemia, low CD4 counts and high CRP were associated with lower physical activity and capacity. In HIV-uninfected individuals, abdominal obesity and moderate anaemia were associated with lower physical activity and capacity. CONCLUSION: HIV-infected participants had lower levels of physical activity and capacity than HIV-uninfected participants. Correlates of physical activity and capacity differed by HIV status. Management of HIV and related conditions needs to be provided effectively in health care facilities. Interventions promoting physical activity in these populations will be of importance to improve their health and reduce the risk of non-communicable diseases.

Association of schistosome infection with adiposity in Tanzania.

Background: Observational studies in humans have reported a link between schistosome infection and lower adiposity, but this may be explained by socioeconomic and demographic factors, intensity of infection, or common co-infections such as HIV. Methods: This was a cross-sectional study that investigated the relationship between schistosome infection and adiposity in a large, well-described cohort of Tanzanian adults living with and without HIV. Cross-sectional data were collected among adults living in Mwanza, Tanzania who were enrolled in the Chronic Infections, Co-morbidities and Diabetes in Africa (CICADA) cohort study. Schistosome circulating anodic antigen, secreted by both Schistosoma mansoni and haematobium which are endemic to Tanzania, was quantified from stored samples. Schistosome infection diagnosed by serum circulating anodic antigen levels. The primary outcome was fat mass measured by bioimpedance analysis. Secondary outcomes included fat-free mass, waist circumference, mid-upper arm circumference, and body mass index. Results: The study enrolled 1,947 adults, of whom 1,923 (98.8%) had serum available for schistosome testing. Of these, 873 (45.4%) had a serum circulating anodic antigen ≥30 pg/mL, indicating schistosome infection. Compared to uninfected individuals, those with schistosome infections had -1.1 kg [95% CI -1.9 to -0.3] lower fat mass after adjusting for age, sex, physical activity, tobacco use, education level, and socioeconomic status. Infected participants also had lower waist circumference, mid-upper arm circumference, and body mass index. Fat-free mass was not different between the two groups. Neither being HIV-infected, nor receiving antiretroviral therapy, modified associations between schistosome infection and adiposity. These associations were also not affected by Schistosoma worm burden. Conclusions: Schistosome infection was associated with lower fat mass and less central adiposity without a difference in muscle mass, irrespective of confounders, HIV status, or the intensity of schistosome infection. Future studies should adjust for socioeconomic and demographic factors that are associated with schistosome infection and adiposity. Identifying mechanistic pathways by which schistosome infection reduces adiposity while preserving muscle mass could yield new strategies for obesity control and cardiovascular disease prevention.

Risk factors for impaired renal function in HIV-infected and HIV-uninfected adults: cross-sectional study in North-Western Tanzania.

BACKGROUND: Although the burden of impaired renal function is rising in sub-Saharan Africa (SSA), little is known about correlates of impaired renal function in the region. We determined factors associated with estimated glomerular filtration rate (eGFR) and impaired renal function in HIV-infected and HIV-uninfected adults. METHODS: We undertook cross-sectional analysis of data from 1947 adults at enrolment for a cohort study on diabetes and associated complications in HIV patients in Mwanza, north-western Tanzania. A structured questionnaire was used to collect data on sociodemography, smoking, alcohol, physical activity, antiretroviral therapy (ART) and anthropometry. We measured blood pressure, tested blood samples for creatinine, glucose and HIV, and performed Kato Katz for Schistosoma mansoni. Correlates of eGFR (mL/min/1.73 m2) and impaired renal function (eGFR< 60 mL/min/1.73 m2) were determined using linear regression and logistic regression, respectively. RESULTS: 655 (34%) participants were HIV-uninfected, 956 (49%) were ART-naive HIV-infected and 336 (17%) were HIV-infected adults on ART. The mean age was 41 years (SD12) and majority (59%) were females. Overall, the mean eGFR was 113.6 mL/min/1.73 m2 but 111.2 mL/min/1.73 m2 in HIV-uninfected, 109.7 mL/min/1.73 m2 in ART-naive HIV-infected and 129.5 mL/min/1.73 m2 in HIV-infected ART-experienced adults, and respective prevalence of impaired renal function was 7.0, 5.7, 8.1 and 6.3%. Correlates of lower eGFR were increasing age, higher socioeconomic status, unhealthy alcohol drinking, higher body mass index and diabetes mellitus. Anaemia was associated with 1.9 (95% Confidence Interval (CI):1.2, 2.7, p = 0.001) higher odds of impaired renal function compared to no anaemia and this effect was modified by HIV status (p value 0.02 for interaction). CONCLUSION: Impaired renal function is prevalent in this middle-aged study population. Interventions for prevention of impaired renal function are needed in the study population with special focus in HIV-infected adults and those with high socioeconomic status. Interventions targeting modifiable risk factors such as alcohol and weight reduction are warranted.

ß-cell dysfunction and insulin resistance in relation to pre-diabetes and diabetes among adults in north-western Tanzania: a cross-sectional study.

OBJECTIVE: Studies on phenotypes of diabetes in Africa are inconsistent. We assessed the role of ß-cell dysfunction and insulin resistance on pre-diabetes and diabetes. METHODS: We included 1890 participants with mean age of 40.6 (SD11.9) years in a cross-sectional study among male and female adults in Tanzania during 2016 to 2017. Data on C-reactive protein (CRP), alpha-acid glycoprotein (AGP), HIV, oral glucose tolerance test (OGTT), body composition and insulin were collected. Insulinogenic index and HOMA-IR were used to derive an overall marker of ß-cell dysfunction and insulin resistance which was categorised as follows: normal ß-cell function and insulin sensitivity, isolated ß-cell dysfunction, isolated insulin resistance, and combined ß-cell dysfunction and insulin resistance. Pre-diabetes and diabetes were defined as 2-hour OGTT glucose between 7.8-11.0 and ≥ 11.1 mmol/L, respectively. Multinomial regression assessed the association of ß-cell dysfunction and insulin resistance with outcome measures. RESULTS: ß-cell dysfunction, insulin resistance, and combined ß-cell dysfunction and insulin resistance were associated with higher pre-diabetes risk. Similarly, isolated ß-cell dysfunction (adjusted relative risk ratio (aRRR) 4.8 (95% confidence interval (CI) 2.5, 9.0), isolated insulin resistance (aRRR 3.2 (95% CI 1.5, 6.9), and combined ß-cell dysfunction and insulin resistance (aRRR 35.9 (95% CI 17.2, 75.2) were associated with higher diabetes risk. CRP, AGP and HIV were associated with higher diabetes risk, but fat mass was not. 31%, 10% and 33% of diabetes cases were attributed to ß-cell dysfunction, insulin resistance, and combined ß-cell dysfunction and insulin resistance, respectively. CONCLUSIONS: ß-cell dysfunction seemed to explain most of diabetes cases compared to insulin resistance in this population. Cohort studies on evolution of diabetes in Africa are needed to confirm these results.

Diabetes prevalence by HbA1c and oral glucose tolerance test among HIV-infected and uninfected Tanzanian adults.

BACKGROUND: The burden of diabetes is increasing in sub-Saharan Africa, including among people living with HIV. We assessed the prevalence of diabetes and the roles of HIV, antiretroviral therapy (ART) and traditional risk factors among adults in Tanzania. METHODS: We analysed diabetes-relevant baseline data from 1,947 adult participants in the CICADA study in Mwanza, Tanzania: 655 HIV-uninfected, 956 HIV-infected ART-naïve, and 336 HIV-infected persons on ART. WHO guidelines for haemoglobin A1c (HbA1c) and oral glucose tolerance test (OGTT) were used to define diabetes and prediabetes. Risk factors were evaluated using multinomial logistic regression analysis. Relative risk ratios (RRR) were generated comparing participants with diabetes and prediabetes against the reference of those with no diabetes. RESULTS: Mean age was 41 (SD 12) years; 59% were women. The prevalence of diabetes was 13% by HbA1c and 6% by OGTT, with partial overlap among participants identified by the two tests. Relative to HIV-uninfected, HIV-infected ART-naïve persons had increased relative risks of diabetes (HbA1c: RRR = 1.95, 95% CI 1.25-3.03; OGTT: RRR = 1.90, 95% CI 0.96-3.73) and prediabetes (HbA1c: RRR = 2.89, 95% CI 1.93-4.34; OGTT: RRR = 1.61, 95% CI 1.22-2.13). HIV-infected participants on ART showed increased risk of prediabetes (RRR 1.80, 95% CI 1.09, 2.94) by HbA1c, but not diabetes. CD4 count < 200 cell/µL at recruitment increased risk and physical activity decreased risk of diabetes by both HbA1c and OGTT. CONCLUSIONS: The prevalence of diabetes was high, especially among HIV-infected ART-naïve adults. Being more physically active was associated with lower risk of diabetes. HbA1c and OGTT identified different participants as having diabetes or prediabetes. Overall, the finding of high burden of diabetes among HIV-infected persons suggests that health systems should consider integrating diabetes screening and treatment in HIV clinics to optimize the care of HIV patients and improve their health outcomes.

Growth Status, Inflammation, and Enteropathy in Young Children in Northern Tanzania.

Recent evidence suggests that enteropathy of the gut due to environmental conditions (i.e., environmental enteropathy [EE]) in young children is negatively associated with linear growth. Using a case-control study design, we examined the potential determinants of stunting in stunted and non-stunted children 22-28 months of age. Potential determinants included inflammation biomarkers C-reactive protein, alpha-1-acid glycoprotein (AGP), and endotoxin-core antibody (EndoCAb) measured in serum samples; enteropathy markers alpha-1-antitrypsin, neopterin, myeloperoxidase (MPO) measured in stools samples; and demographic, health, feeding, and household characteristics. We also explored the determinants of EE by testing associations of composite EE scores and individual biomarkers with potential risk factors. Fifty-two percent of children (n = 310) were found to be stunted, and mean height-for-age Z scores (HAZ) were -1.22 (standard deviation [SD] ± 0.56) among non-stunted (control) children and -2.82 (SD ± 0.61) among stunted (case) children. Child HAZ was significantly (P < 0.05) and inversely associated with AGP, and child stunting was significantly positively associated (P < 0.05) with low dietary diversity, severe household hunger, and absence of soap in the household. Alpha-1-acid glycoprotein and EndoCAb concentrations were also significantly higher (P < 0.05) among children in households with no soap. Our study documented a seemingly localized cultural practice of young children (25%) being fed their dirty bathwater, which was associated with significantly higher concentrations of MPO (P < 0.05). Alpha-1-acid glycoprotein showed the most consistent associations with child growth and hygiene practices, but fecal EE biomarkers were not associated with child growth. The lack of retrospective data in our study may explain the null findings related to fecal EE biomarkers and child growth.