Clinical characteristics and outcomes of people living with HIV and ocular syphilis during the COVID-19 health emergency.

BACKGROUND: The global shift in healthcare during the COVID-19 pandemic led to challenges in the care of people living with HIV. METHODS: We conducted a retrospective study that aimed to delineate sociodemographic, clinical characteristics and outcomes, of people living with HIV diagnosed with ocular syphilis. RESULTS: Fifty-three people living with HIV were identified with ocular syphilis. Thirty-eight (71.6%) presented ocular symptoms. Twenty-three (43.3%) underwent lumbar puncture, 5 (9.4%) were positive for neurosyphilis. Forty-seven (88.6%) received treatment, 32 (68%) received standard treatment with aqueous crystalline penicillin G, and 15 (31.9%) were treated with alternative regimens due to the impossibility of hospitalization. Six (11.3%) individuals were lost to follow-up and/or did not receive treatment. Eighteen (56.2%) out of 32 individuals in the aqueous crystalline penicillin G group experienced serological response, 5 (15.6%) experienced treatment failure, and 9 (28.1%) were lost to follow-up. In the alternative therapy group, 12 out of 15 individuals (80%) experienced serological response. One (6.7%) experienced treatment failure, and 2 (13.3%) were lost to follow-up. CONCLUSIONS: During the COVID-19 health emergency in Mexico, alternative treatments for ocular syphilis demonstrated favorable clinical outcomes amid challenges in accessing hospitalization.

Individual and community level factors associated with discriminatory attitudes against people living with HIV/AIDS among women of reproductive age in three sub-Saharan African countries: evidence from the most recent demographic and health survey (2021/22).

INTRODUCTION: HIV-related stigma and discrimination significantly affects health, and well-being, willingness to be tested for HIV, initiation and adherence to antiretroviral therapy, and quality of life. However, the findings of the prior studies revealed that the prevalence of discrimination against people living with HIV is high. Thus, we aimed to assess the magnitude of discriminatory attitudes against people living with HIV/AIDS and associated factors in three sub-Saharan African countries. METHODS: The appended and most recent Demographic and Health Survey dataset of three sub-Saharan African countries from 2021 to 2022 was used for data analysis. A total of 56,690 women aged 15-49 years were included in this study as a weighted sample. The determinants of discriminatory attitudes against people living with HIV/AIDS were determined using a multilevel mixed-effects logistic regression model. Significant factors associated with discriminatory attitudes against people living with HIV/AIDS in the multilevel mixed-effect logistic regression model were declared significant at p-values < 0.05. The adjusted odds ratio (AOR) and confidence interval (CI) were used to interpret the results. RESULT: The overall prevalence of discriminatory attitudes against people living with HIV/AIDS was 28.19% (95% CI: 27.74%, 28.64%). In the multivariable analysis, individual level (being young, being an internet user, being tested for HIV, and having comprehensive knowledge about HIV) and community level (being a rural dweller) were factors associated with discriminatory attitudes against people living with HIV/AIDS. CONCLUSION: The prevalence of discriminatory attitudes against people living with HIV/AIDS in three sub-Saharan African countries was high. Individual and community-level variables were associated with discriminatory attitudes against people living with HIV/AIDS. Therefore, special consideration should be given to rural dwellers and young adults. In addition, better to strengthen the accessibility of Internet and HIV testing services, and improve HIV-related education to reduce the magnitude of discriminatory attitudes against people living with HIV/AIDS.

Weight change with antiretroviral switch from integrase inhibitor or tenofovir alafenamide-based to Doravirine-Based regimens in people with HIV.

BACKGROUND: Weight gain has been well-described with integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF). Doravirine (DOR) has been identified as a relatively "weight-neutral" drug; however, there is little data describing its effect on weight change in routine clinical practice. METHODS: We conducted a retrospective chart review of weight change among people with HIV changing from an INSTI- to a non-INSTI regimen with DOR. RESULTS: At the time of ART switch, among 49 people with HIV, the mean age was 47 years, 24% were female, and 75% had HIV-1 viral load <200 copies/mL. Most (55%) people with HIV were taking bictegravir/TAF/emtricitabine prior to the switch. Although 84% switched due to concerns about weight gain, only 16% had a weight gain of ≥10% in the year preceding, and 49% had no substantial change in weight. 86% switched to DOR/lamivudine/tenofovir disoproxil fumarate. A weight decrease (-2.6% [95% CI: -5.1, -0.1%, p = .041] was seen over the year following the ART switch. Weight change prior to switch was greatest in the year 2021 compared to 2019, 2020, and 2022. CONCLUSIONS: Overall, modest changes in weight were seen following ART switch from INSTI-based regimen to a DOR-based, non-INSTI regimen. Further investigations with larger people with HIV cohorts will be helpful to guide clinical practice, while the impact of the COVID-19 pandemic on weight change should also be considered.

Development of normal reference intervals for renal function in pregnancy: a secondary analysis of clinical trial data.

BACKGROUND: Due to its potential nephrotoxicity, screening for pre-existing renal function disorders has become a routine clinical assessment for initiating Tenofovir diphosphate fumarate (TDF)-containing antiretroviral treatment (ART) or pre-exposure prophylaxis (PrEP) in pregnant and non-pregnant adults. We aimed to establish reference values for commonly used markers of renal function in healthy pregnant women of African origin. METHODS: Pregnant women ≥18 years, not living with HIV, and at 14-28 weeks gestation were enrolled in a PrEP clinical trial in Durban, South Africa between September 2017 and December 2019. Women were monitored 4-weekly during pregnancy until six months postpartum. We measured maternal weight and serum creatinine (sCr) at each visit and calculated creatinine clearance (CrCl) rates using the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulae. Reference ranges for sCr and CrCl by CG and MDRD calculations were derived from the mean ± 2SD of values for pregnancy and postdelivery. RESULTS: Between 14--and 40 weeks gestation, 249 African women not exposed to TDF-PrEP contributed a total of 1193 renal function values. Postdelivery, 207 of these women contributed to 800 renal function values. The normal reference range for sCr was 30-57 and 32-60 umol/l in the 2nd and 3rd trimesters of pregnancy. Normal reference ranges for CrCl using the MDRD calculation were 129-282 and 119-267 ml/min/1.73m2 for the 2nd and 3rd trimesters, respectively. Using the CG method of calculation, normal reference ranges for CrCl were 120-304 and 123-309 ml/min/1.73m2 for the 2nd and 3rd trimesters respectively. In comparison, the normal reference range for sCr, CrCl by MDRD and CG calculations postpartum was 40-77 umol/l, 92-201, and 90-238 ml/min/1.73m2, respectively. CONCLUSIONS: In African women, the Upper Limit of Normal (ULN) for sCr in pregnancy is approximately 20% lower than 6 months postnatally. Inversely, the Lower Limit of Normal (LLN) for CrCl using either MDRD or CG equation is approximately 35% higher than 6 months postnatally. We provide normal reference ranges for sCr and CrCl for both methods of calculation and appropriate for the 2nd and 3rd trimesters of pregnancy in African women.

Screening for pre-existing renal function disorders has become a routine clinical assessment for initiating TDF-containing antiretroviral treatment or pre-exposure prophylaxis in adults including pregnant women. Pregnancy inherently increases renal function, hence normal reference standards for non-pregnant adults cannot be used for pregnant women. In a secondary analysis of data from a healthy pregnant population not living with HIV who participated in a PrEP clinical trial, we established reference intervals for serum creatinine (sCr) concentration and creatinine clearance (CrCl) during pregnancy and postpartum in an African population. Using sCr and CrCl values for 249 healthy pregnant African women, we can confirm that the upper limit of normal for sCr in pregnancy is 20% lower than that for the 6-month postnatal period and recommend an upper limit of 57 umol/l and 60 umol/l in the second and third trimesters respectively to determine normal renal function in pregnant African women.We further determined the lower limit of normal for creatinine clearance using two methods of calculation, which was 35% higher than that of the postnatal period. Using the modification of diet in renal disease calculation, we recommend a lower limit of 129 and 119 ml/min/1.73m² for the second and third trimesters respectively. Using the Cockcroft­Gault calculation, we recommend a lower limit of 120 and 123 ml/min/1.73m² for the second and third trimesters respectively. Using current standard cut-off values estimated for adults may lead to underreporting of abnormal renal function in African pregnant women.

Potential for high dynamic range Sedia Limiting Antigen antibody assay to support viral load monitoring during antiretroviral therapy.

INTRODUCTION: Viral Load (VL) monitoring is a crucial component of patient care during antiretroviral therapy (ART) but is not routinely available in many resource-constrained settings, where millions of patients will require care for decades to come. We hypothesise a serologic 'recent infection' test (Sedia LAg assay) which has a high dynamic range for detecting antigen-driven antibody response can provide informative proxies for VL trajectories. METHODS: A retrospective study where we analysed data linked via specimens in a well-described repository for recent infection test benchmarking (CEPHIA collaboration). Patient panels were comprised of 1) observations straddling ART start; 2) observations from a period of stable viral suppression; 3) observations straddling rebound after a period of viral suppression. We analysed an individual's Sedia LAg ELISA normalised optical density (ODn) trends within these categories. Using groups 2) and 3) we evaluated the specificity and sensitivity of a proposed proxy for "the latest observation is at a time of VL rebound"; proxy was defined as follows: we estimated patient-specific mean-previous-ODn for all observations with at least two preceding virally suppressed observations. We considered various thresholds to define both "VL suppression" and "ODn uptick". RESULTS: In regression analysis by category: 1) ODn gradients are statistically significantly negative just after ART-start (p = 0.010); 2) During periods of stable viral suppression, ODn tended to decline, but not statistically significantly, for a range of clinically meaningful "VL suppression" thresholds; 3) comparing ODn values just before, versus at, "VL rebound", ODn changes were statistically significantly increasing at rebound (p = 0.001). In the analysis comparing groups 2) and 3), at a Z score threshold of 0.8, the proposed proxy for a first viral rebound had an observed specificity and sensitivity both close to 90%. CONCLUSION: The high dynamic range of serological tests previously investigated for defining 'recent infection' has potential, as demonstrated using the Sedia LAg ELISA, to provide meaningful information about the success of ART, during treatment initiation, at times of stable suppression, and to flag possible viral rebound. It should be investigated how this can be combined with patient management workflows and (clinical and) other data, to provide efficiencies in long-term monitoring viral control in resource-limited settings.

Successful management of haemophagocytic lymphohistiocytosis in an adolescent with newly diagnosed HIV/AIDS and histoplasmosis.

Haemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening hyperinflammatory syndrome characterised by persistent fevers, cytopenia, hepatosplenomegaly and systemic inflammation. Secondary HLH can be triggered by various aetiologies including infections, malignancies and autoimmune conditions. We highlight the complexity of HLH diagnosis and management by describing a case of an adolescent Salvadoran immigrant with HLH, newly diagnosed HIV, Streptococcal bacteraemia and disseminated histoplasmosis. The patient presented with neurological and ocular findings along with persistent fevers and cytopenia. He was diagnosed with HLH and treated with anakinra in addition to receiving treatment for HIV, Streptococcal bacteraemia and histoplasmosis. The patient's HLH resolved without corticosteroids or chemotherapy, which are considered the mainstays for HLH treatment. This case underscores the need for the evaluation and management of multiple infections and individualised management in patients presenting with HLH to achieve favourable outcomes.

Cohort profile: longitudinal and population comparison of children who are HIV-exposed uninfected and children who are HIV unexposed in Kenya (HOPE study).

PURPOSE: Globally, the number of children/adolescents exposed to HIV but uninfected (HIV-exposed uninfected, HEU) is growing. The HEU outcomes: population-evaluation and screening strategies study was designed to provide population-level evidence of the impact of HIV and recent antiretroviral therapy regimen exposure on neurodevelopmental, hearing and mental health outcomes from infancy to adolescence. PARTICIPANTS: The study includes a prospective mother-infant cohort and cross-sectional child/youth-caregiver cohorts conducted in Kenya.Between 2021 and 2022, the study enrolled 2000 mother-infant pairs (1000 HEU and 1000 HIV-unexposed uninfected (HUU)) for longitudinal follow-up. Infants were eligible if they were aged 4-10 weeks and healthy. Mothers were eligible if their HIV status was known and were ≥18 years. Study visits are 6 monthly until the child reaches age 3 years.Cross-sectional cohorts spanning ages 3-18 years started enrolment in 2022. Target enrolment is 4400 children/youth (4000 HEU and 400 HUU). Children and youth are eligible if they are HIV negative, maternal HIV status and timing of diagnosis is known, and caregivers are ≥18 years.Data on infant/child/youth growth, neurodevelopment, mental health, morbidity and hearing are collected at enrolment using standardised tools. Dry blood spots samples are collected for telomere length assessment at baseline and yearly for the longitudinal cohort. Growth z-scores, neurodevelopmental scores, telomere length and prevalence of developmental and hearing problems will be compared between HEU/HUU populations. FINDINGS TO DATE: Full cohort enrolment for the longitudinal cohort is complete and participants are in follow-up. At 1 year of age, comparing HEU to HUU neurodevelopment using the Malawi developmental assessment tool, we found that HEU infants had higher language scores and comparable scores in fine motor, gross motor and social scores. The cross-sectional cohort has enrolled over 2000 participants and recruitment is ongoing. FUTURE PLANS: Longitudinal cohort follow-up and enrolment to the cross-sectional study will be completed in June 2024.

Depression symptoms and suicidal ideation among HIV infected Rwandans: the mediating and moderating effects of complicated grief and substance abuse.

BACKGROUND: People with HIV/AIDS (PWHA) have 7-36 times greater risk for completed suicide associated with depression symptoms compared to general population. However, no study has sufficiently analyzed the mediating or moderating variables of the relationship between depression and suicidal ideation in Rwanda. OBJECTIVES: This study aimed to examine how complicated grief mediates and substance abuse moderates the effects of depression symptoms on suicidal ideation. METHODS: Data were collected from a convenient sample of 140 participants (M-age = 38.79 years, SD = 10.218) receiving antiretroviral therapy (ART) at Remera Health Center in a cross-sectional study. Multiple linear regression and Sobel test were used to examine the relationships between depression symptoms, complicated grief, suicidal ideation, and substance abuse. RESULTS: The results indicated that 29% of the sample had clinically significant symptoms of depression and 18% had suicidal ideation. The interaction between substance abuse and depression symptoms (ß = .468, t = 8.02, p = 0.000) was a significant predictor, explaining the 55.7% of variance in suicidal ideation. Furthermore, the Sobel test demonstrated that complicated grief mediated the effects of depression symptoms (t = 4.67, SE = 0.0101, p ≤ 0.001) on suicidal ideation. CONCLUSION: The results suggest that depression symptoms are associated with an increased risk of suicidal ideation, and this risk significantly amplified in the presence of complicated grief and substance abuse. These findings highlight the importance of integrating mental health services, particularly those addressing depression, complicated grief, and substance abuse, into HIV care programs to mitigate the risk of suicidal ideation among PWHA.

Low clinical impact of HIV drug resistance mutations in oral pre-exposure prophylaxis: a systematic review and meta-analysis.

INTRODUCTION: Despite the widespread use of pre-exposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) transmission, scant information on HIV drug resistance mutations (DRMs) has been gathered over the past decade. This review aimed to estimate the pooled prevalence of pre-exposure prophylaxis and its two-way impact on DRM. METHODS: We systematically reviewed studies on DRM in pre-exposure prophylaxis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines. PubMed, Cochrane, and SAGE databases were searched for English-language primary studies published between January 2001 and December 2023. The initial search was conducted on 9 August 2021 and was updated through 31 December 2023 to ensure the inclusion of the most recent findings. The registration number for this protocol review was CRD42022356061. RESULTS: A total of 26,367 participants and 562 seroconversion cases across 12 studies were included in this review. The pooled prevalence estimate for all mutations was 6.47% (95% Confidence Interval-CI 3.65-9.93), while Tenofovir Disoproxil Fumarate/Emtricitabine-associated drug resistance mutation prevalence was 1.52% (95% CI 0.23-3.60) in the pre-exposure prophylaxis arm after enrolment. A subgroup analysis, based on the study population, showed the prevalence in the heterosexual and men who have sex with men (MSM) groups was 5.53% (95% CI 2.55-9.40) and 7.47% (95% CI 3.80-12.11), respectively. Notably, there was no significant difference in the incidence of DRM between the pre-exposure prophylaxis and placebo groups (log-OR = 0.99, 95% CI -0.20 to 2.18, I2 = 0%; p = 0.10). DISCUSSION: Given the constrained prevalence of DRM, the World Health Organization (WHO) advocates the extensive adoption of pre-exposure prophylaxis. Our study demonstrated no increased risk of DRM with pre-exposure prophylaxis (p > 0.05), which is consistent with these settings. These findings align with the previous meta-analysis, which reported a 3.14-fold higher risk in the pre-exposure prophylaxis group than the placebo group, although the observed difference did not reach statistical significance (p = 0.21). CONCLUSIONS: Despite the low prevalence of DRM, pre-exposure prophylaxis did not significantly increase the risk of DRM compared to placebo. However, long-term observation is required to determine further disadvantages of extensive pre-exposure prophylaxis use. PROSPERO Number: CRD42022356061.

Use of dental care services among adolescents living with HIV on antiretroviral treatment in Kampala, Uganda: a cross-sectional study.

OBJECTIVE: The primary purpose of this study was to assess the prevalence and socio-behavioral determinants of ever-use of dental care services among adolescents aged 10-18 years, living with HIV, on Antiretroviral treatment (ART), and attending selected HIV clinics in Kampala, Uganda. METHODS: A cross-sectional study was carried out between March and September 2020. The study conveniently recruited 154 adolescents between 10 and 18 years old from 4 specific HIV clinics in Kampala. Andersen's behavioral model guided the selection of variables, with the ever-use of dental care services as the outcome and predisposing, enabling, need-related factors and personal dental health practices as exposure variables. Data were analyzed using Fischer's exact test for cross-tabulation and modified Poisson regression for multivariate analysis. RESULTS: The prevalence of ever-use of dental care services was 12.3%. The adolescents aged 14-18 had higher odds of using dental care services (Prevalence ratio (PR) of 3.35 than those aged 10-13 years. Fear of the spread of HIV was negatively associated with ever-use of dental care services (PR of 0.06). Participants who were afraid of going to the dentist had higher odds of using dental care services (PR of 2.98) than those not afraid. Failure to receive dental treatment because it was not part of the medical appointment had a positive association with the ever-use of dental care services (PR of 4.50). Those who were satisfied with their dental condition had lower odds of using dental care services. The bad oral odor was positively associated with the ever-use of dental care services (PR of 2.80). The use of soap for toothbrushing was positively associated with the ever-use of dental care services (PR of 2.51). CONCLUSION: The study found a low frequency of dental care use among HIV-infected adolescents in Kampala, Uganda, with age being a predisposing factor. Enabling factors included fear of HIV spread, medical-dental appointment incoordination, and satisfaction with the dental condition and bad oral odor while under personal dental health practices. The use of soap for toothbrushing was an important association with dental care. Nevertheless, these study results cannot be generalized to the entire HIV adolescent population in Uganda.

A helping HAND: therapeutic potential of MAGL inhibition against HIV-1-associated neuroinflammation.

Background: Human immunodeficiency virus (HIV) affects nearly 40 million people globally, with roughly 80% of all people living with HIV receiving antiretroviral therapy. Antiretroviral treatment suppresses viral load in peripheral tissues but does not effectively penetrate the blood-brain barrier. Thus, viral reservoirs persist in the central nervous system and continue to produce low levels of inflammatory factors and early viral proteins, including the transactivator of transcription (Tat). HIV Tat is known to contribute to chronic neuroinflammation and synaptodendritic damage, which is associated with the development of cognitive, motor, and/or mood problems, collectively known as HIV-associated neurocognitive disorders (HAND). Cannabinoid anti-inflammatory effects are well documented, but therapeutic utility of cannabis remains limited due to its psychotropic effects, including alterations within brain regions encoding reward processing and motivation, such as the nucleus accumbens. Alternatively, inhibiting monoacylglycerol lipase (MAGL) has demonstrated therapeutic potential through interactions with the endocannabinoid system. Methods: The present study utilized a reward-related operant behavioral task to quantify motivated behavior in female Tat transgenic mice treated with vehicle or MAGL inhibitor MJN110 (1 mg/kg). Brain tissue was collected to assess dendritic injury and neuroinflammatory profiles, including dendritic microtubule-associated protein (MAP2ab) intensity, microglia density, microglia morphology, astrocyte density, astrocytic interleukin-1ß (IL-1ß) colocalization, and various lipid mediators. Results: No significant behavioral differences were observed; however, MJN110 protected against Tat-induced dendritic injury by significantly upregulating MAP2ab intensity in the nucleus accumbens and in the infralimbic cortex of Tat(+) mice. No or only minor effects were noted for Iba-1+ microglia density and/or microglia morphology. Further, Tat increased GFAP+ astrocyte density in the infralimbic cortex and GFAP+ astrocytic IL-1ß colocalization in the nucleus accumbens, with MJN110 significantly reducing these measures in Tat(+) subjects. Lastly, selected HETE-related inflammatory lipid mediators in the striatum were downregulated by chronic MJN110 treatment. Conclusions: These findings demonstrate anti-inflammatory and neuroprotective properties of MJN110 without cannabimimetic behavioral effects and suggest a promising alternative to cannabis for managing neuroinflammation.

Phase 1 randomized trials to assess safety, pharmacokinetics, and vaginal bleeding associated with use of extended duration dapivirine and levonorgestrel vaginal rings.

BACKGROUND: Vaginal rings formulated to deliver two drugs simultaneously have potential as user-controlled, long-acting methods for dual prevention of HIV and pregnancy. METHODS: Two phase 1 randomized trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019) respectively enrolled 24 and 25 healthy, HIV-negative participants to evaluate safety, pharmacokinetics, and vaginal bleeding associated with use of a vaginal ring containing 200mg dapivirine (DPV) and 320mg levonorgestrel (LNG) designed for 90-day use. MTN-030/IPM 041 compared the DPV/LNG ring to a DPV-only ring (200mg) over 14 days of use. MTN-044/IPM 053/CCN019 compared continuous or cyclic use of the DPV/LNG ring over 90 days of use. Safety was assessed by recording adverse events (AEs). DPV and LNG concentrations were quantified in plasma, cervicovaginal fluid, and cervical tissue. Vaginal bleeding was self-reported. RESULTS: There were no differences in the proportion of participants with grade ≥2 genitourinary AEs or grade ≥3 AEs with DPV/LNG ring vs. DPV ring use (p = .22), or with DPV/LNG ring continuous vs. cyclic use (p = .67). Higher plasma DPV concentrations were observed in users of DPV/LNG compared to DPV-only rings (Cmax p = 0.049; AUC p = 0.091). Plasma DPV and LNG concentrations were comparable with continuous and cyclic use (Cmax p = 0.74; AUC p = 0.25). With cyclic use, median nadir plasma DPV concentration was approximately 300 pg/mL two days after removal and median t1/2 for cervicovaginal fluid DPV concentration was 5.76 hours (n = 3). Overall bleeding experiences did not differ between continuous and cyclic users (p = 0.12). CONCLUSIONS: The extended duration DPV/ LNG rings were well tolerated and the observed DPV concentrations in plasma and cervicovaginal fluid when used continuously exceeded concentrations observed in previous DPV ring efficacy studies. LNG concentrations in plasma were comparable with other efficacious LNG-based contraceptives. Genital DPV concentrations had a short half-life and were thus not well sustained following ring removal.

Coprevalence and associations of diabetes mellitus and hypertension among people living with HIV/AIDS in Cameroon.

BACKGROUND: The association between HIV infection and increased cardiometabolic risk, attributed to chronic inflammation in people living with HIV (PLWH) and/or antiretroviral therapy (ART) effects, has been inconsistent. In this study, we aimed to assess the associations of HIV-related factors with hypertension (HTN) and type-2 diabetes mellitus (T2DM), and the potential mediation effects of body mass index (BMI) in the associations between ART use and HTN or T2DM in PLWH in Cameroon. METHODS: A cross-sectional study was conducted with 14,119 adult PLWH from Cameroon enrolled in the International epidemiology Databases to Evaluate AIDS (IeDEA) between 2016 and 2021. HTN was defined as systolic/diastolic blood pressure ≥ 140/90 mmHg and/or current use of antihypertensive medication, while T2DM was defined as fasting blood sugar ≥ 126 mg/dL and/or use of antidiabetic medications. Univariable and multivariable multinomial logistic regression analyses examined the associations of factors with HTN alone, T2DM alone, and both (HTN + T2DM). Mediation analyses were conducted to assess the potential mediation roles of BMI, while controlling for age, sex, and smoking. RESULTS: Of the 14,119 participants, 9177 (65%) were women, with a median age of 42 (25th-75th percentiles: 35-51) years. Age > 50 years was associated with HTN alone, T2DM alone, and HTN + T2DM compared to the age group 19-29 years. Men had higher odds of having HTN + T2DM. Overweight and obesity were predictors of HTN alone compared to being underweight. WHO stages II and III HIV disease were inversely associated with HTN alone compared to stage I. The odds of diabetes alone were lower with ART use. BMI partially mediated the association between ART use and hypertension, with a proportion of mediation effect of 49.6% (all p < 0.02). However, BMI did not mediate the relationship between ART use and diabetes. CONCLUSIONS: Traditional cardiovascular risk factors were strongly associated with hypertension among PLWH, while HIV-related exposures had smaller associations. BMI partially mediated the association between ART use and hypertension. This study emphasizes the importance of screening, monitoring, and managing HTN and T2DM in older, male, and overweight/obese PLWH. Further research on the associations of HIV disease stage and ART use with HTN and T2DM is warranted.

Joint clinical determinants for bivariate hematological parameter among TB/HIV co-infected adults under TB/HIV treatment in university of Gondar comprehensive specialized hospital: Retrospective panel data study.

BACKGROUND: Worldwide ranking above HIV/AIDS, tuberculosis is continues to have a significant effect on public health and the leading cause of death due to high progression of HIV. The objective of current study was identify joint clinical determinants that affecting bivariate hematological parameter among TB/HIV co-infected adults under TB/HIV treatment in university of Gondar comprehensive specialized hospital. METHOD: The result of these study was conducted at university of Gondar comprehensive specialized hospital, Gondar, Ethiopia by using a retrospective cohort follow up study from September 2015-march 2022 G.C. The source of data in this study was secondary data obtained from patients chart. Bayesian approach of longitudinal linear mixed effect sub model was used in panel data set to get wide range of information about TB/HIV co-infected patients. RESULT: Out of 148 co-infected participants more than half of the patients (56.1%) and (52.7%) accounted for CPT and INH non users, of which 10.8% and 10.3% had the outcome of mortality respectively. The random intercept and slope model were selected for repeated measure hemoglobin level and hematocrit based on deviance information criteria (DIC), and probability of direction (Pd) under the full model. CONCLUSION: Current study revealed that clinical predictors red blood cell count, platelet cell count, fair and good treatment adherence, other ART regiment, IPT drug users, and viral load count < 10,000 copies/mL, were associated with high hemoglobin level concentration while, lymphocyte count, WHO clinical stage-IV,1e ART regiment, and patients with OIs results for low hemoglobin level concentration. Likewise, red blood cell count, platelet cell count, fair and good treatment adherence, IPT drug users, and viral load count < 10,000 copies/mL co-infected patients had high hematocrit, while lymphocyte count, WHO clinical stage-III,1c ART regiment, and patients with OIs significantly leads to low hematocrit. Health professionals give more attention to these important predictors to reduce progression of disease when the co-infected patients come back again in the hospital. In addition, health staff should conduct health related education for individuals to examine continuous check-up of co-infected patients.

Post-intervention perceptions on the antiretroviral therapy community group model in Trans Nzoia County, Kenya.

Introduction: the increasing number of people receiving antiretroviral therapy (ART) in sub-Saharan Africa has stressed already overburdened health systems. A care model utilizing community-based peer-groups (ART Co-ops) facilitated by community health workers (CHW) was implemented (2016-2018) to address these challenges. In 2018, a post-intervention study assessed perceptions of the intervention. Methods: forty participants were engaged in focus group discussions consisting of ART Co-op clients, study staff, and health care providers from Kitale HIV clinic. Data were analyzed thematically for content on the intervention, challenges, and recommendations for improvement. Results: all participants liked the intervention. However, some reported traveling long distances to attend ART Co-op meetings and experiencing stigma with ART Co-ops participation. The ART Co-op inclusion criteria were considered appropriate; however, additional outreach to deliberately include spouses living with HIV, the disabled, the poor, and HIV pregnant women was recommended. Participants liked CHW-directed quarterly group meetings which included ART distribution, adherence review, and illness identification. The inability of the CHW to provide full clinical care, inconvenient meeting venues, poor timekeeping, and non-attendance behaviors were noted as issues. Participants indicated that program continuation, regular CHW training, rotating meetings at group members´ homes, training ART Co-ops leaders to assume CHW tasks, use of pill diaries to check adherence, nutritional support, and economically empowering members through income generation projects would be beneficial. Conclusion: the intervention was viewed positively by both clinic staff and clients. They identified specific challenges and generated actionable key considerations to improve access and acceptability of the community-based model of care.

Alzheimer-Type Cerebral Amyloidosis in the Context of HIV Infection: Implications for a Proposed New Treatment Approach.

Reverse transcriptase inhibitors (RTIs) are currently broadly prescribed for the treatment of HIV infection but are also thought to prevent Alzheimer's disease (AD) progression by protecting against amyloidosis. Our study evaluates the hypothesis that reverse transcriptase inhibitors protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection. We compiled a case series of participants from a prospective study of the neurological consequences of HIV infection at the HIV Neurobehavioral Research Program (HNRP) who had serial neuropsychological and neurological assessments and were on RTIs. Two participants had gross and microscopic examination and immunohistochemistry of the brain at autopsy; one was assessed clinically for Alzheimer's disease by cerebrospinal fluid (CSF) analysis of phosphorylated-Tau, Total-Tau and Aß42. Additionally, a larger cohort of 250 autopsied individuals was evaluated for presence of amyloid plaques, Tau, and related pathologies. Three older, virally suppressed individuals with HIV who had long-term treatment with RTIs were included in analyses. Two cases demonstrated substantial cerebral amyloid deposition at autopsy. The third case met clinical criteria for AD based on a typical clinical course and CSF biomarker profile. In the larger cohort of autopsied individuals, the prevalence of cerebral amyloidosis among people with HIV (PWH) was greater for those on RTIs. Our study showed that long-term RTI therapy did not protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection in these patients. Given the known toxicities of RTIs, it is premature to recommend them to individuals at risk or with Alzheimer's disease who do not have HIV infection.

The introduction of video-enabled directly observed therapy (video-DOT) for patients with drug-resistant TB disease in Eswatini amid the COVID-19 pandemic - a retrospective cohort study.

BACKGROUND: Video-enabled directly observed therapy (video-DOT) has been proposed as an additional option for treatment provision besides in-person DOT for patients with drug-resistant TB (DRTB) disease. However, evidence and implementation experience mainly originate from well-resourced contexts. This study describes the operationalization of video-DOT in a low-resourced setting in Eswatini facing a high burden of HIV and TB amid the emergence of the COVID-19 pandemic. METHODS: This is a retrospectively established cohort of patients receiving DRTB treatment during the implementation of video-DOT in Shiselweni from May 2020 to March 2022. We described intervention uptake (vs. in-person DOT) and assessed unfavorable DRTB treatment outcome (death, loss to care) using Kaplan-Meier statistics and multivariable Cox-regression models. Video-related statistics were described with frequencies and medians. We calculated the fraction of expected doses observed (FEDO) under video-DOT and assessed associations with missed video uploads using multivariable Poisson regression analysis. RESULTS: Of 71 DRTB patients eligible for video-DOT, the median age was 39 (IQR 30-54) years, 31.0% (n = 22) were women, 67.1% (n = 47/70) were HIV-positive, and 42.3% (n = 30) were already receiving DRTB treatment when video-DOT became available. About half of the patients (n = 37; 52.1%) chose video-DOT, mostly during the time when COVID-19 appeared in Eswatini. Video-DOT initiations were lower in new DRTB patients (aHR 0.24, 95% CI 0.12-0.48) and those aged ≥ 60 years (aHR 0.27, 95% CI 0.08-0.89). Overall, 20,634 videos were uploaded with a median number of 553 (IQR 309-748) videos per patient and a median FEDO of 92% (IQR 84-97%). Patients aged ≥ 60 years were less likely to miss video uploads (aIRR 0.07, 95% CI 0.01-0.51). The cumulative Kaplan-Meier estimate of an unfavorable treatment outcome among all patients was 0.08 (95% CI 0.03-0.19), with no differences detected by DOT approach and other baseline factors in multivariable analysis. CONCLUSIONS: Implementing video-DOT for monitoring of DRTB care provision amid the intersection of the HIV and COVID-19 pandemics seemed feasible. Digital health technologies provide additional options for patients to choose their preferred way to support treatment taking, thus possibly increasing patient-centered health care while sustaining favorable treatment outcomes.

Characterization of the intestinal microbiota in MSM with HIV infection.

BACKGROUND: HIV-infected persons demonstrate notable disturbances in their intestinal microbiota; however, the impact of intestinal microbiota on HIV susceptibility in men who have sex with men (MSM), as well as the effects of HIV and antiretroviral therapy (ART) on their gut microbiota, remains under active study. Thus, our research focuses on clarifying the distinctions in intestinal microbiota composition among uninfected MSM and non-MSM healthy controls, investigating the alterations in early-stage intestinal microbial communities following HIV infection, and assessing how ART affects the intestinal microbiota. METHODS: This study enrolled four participant groups: uninfected MSM, Recent HIV-1 infection (RHI) MSM, MSM on ART, and non-MSM healthy controls, with 30 individuals in each group. We utilized 16S ribosomal DNA (16S rDNA) amplicon sequencing to analyze fecal microbiota and employed Luminex multiplex assays to measure plasma markers for microbial translocation (LBP, sCD14) and the inflammatory marker CRP. FINDINGS: Comparing uninfected MSM to non-MSM healthy controls, no substantial variances were observed in α and ß diversity. Uninfected MSM had higher average relative abundances of Bacteroidetes, Prevotella, and Alloprevotella, while Bacteroides, Firmicutes, and Faecalibacterium had lower average relative abundances. MSM on ART had lower intestinal microbiota diversity than RHI MSM and uninfected MSM. In MSM on ART, Megasphaera and Fusobacterium increased, while Faecalibacterium and Roseburia decreased at genus level. Additionally, treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) led to significant alterations in intestinal microbiota diversity and composition compared to RHI MSM. The random forest model showed that HIV infection biomarkers effectively distinguished between newly diagnosed HIV-infected MSM and HIV-negative MSM, with an ROC AUC of 76.24% (95% CI: 61.17-91.31%). CONCLUSIONS: MSM showed early intestinal microbiota imbalances after new HIV infection. MSM on ART experienced worsened dysbiosis, indicating a combined effect of HIV and ART. NNRTI-based treatment notably changed intestinal microbiota, suggesting a potential direct impact of NNRTI drugs on intestinal microbiota.

Assessment of Isoniazid Preventive Therapy and Incidence of Tuberculosis among People Living with Human Immunodeficiency Virus Seeking Care in an Anti-retroviral Therapy Center, Puducherry.

BACKGROUND: One in three deaths among people living with human immunodeficiency virus (PLHIV) is due to Tuberculosis. Isoniazid preventive therapy (IPT) was implemented in antiretroviral therapy (ART) center Puducherry in July 2017. OBJECTIVES: We have determined the proportion of PLHIV who were eligible, initiated, completed IPT and also the incidence of tuberculosis before and after implementation of IPT. MATERIALS AND METHODS: It was a facility based longitudinal descriptive study. All PLHIV, aged 10 years and above, seeking care in ART Centers was included. The number of PLHIV eligible, initiated and completed IPT was summarized as proportion with 95% CI. RESULTS: Among the registered PLHIV (999), the proportion of PLHIV those were found eligible for IPT was 93% [95% CI (91.24%-94.67%)] and initiated on IPT was 92% [95% CI (90.20%-93.95%)]. Completion rate of IPT was 96.3% [95% CI (94.59%-97.63%)]. CONCLUSION: Initiation of IPT was relatively less among newly registered PLHIV as compared to older cohort of PLHIV.