The impact of geriatric syndromes on quality of life among older people living with HIV in Kampala, Uganda.

Objective: Older people living with HIV (OPWH) often have lower quality of life (QoL) compared to general population. Measuring their QoL is an important step in HIV care to ensure they have long healthy lives. This study aimed to evaluate the quality of life and its associated factors among people living with HIV aged 60 years and above in Uganda. Methods: We used a cross-sectional analysis of older people living with HIV (OPWH) enrolled in a prospective cohort from December 2020 - December 2021. Quality of life was assessed using the World Health Organisation QoL OLD instrument (WHOQOL-OLD). Linear regression model was used to determine associated factors. Results: Of the 500 participants enrolled, 51.2% were men and their median age was 64 years (IQR: 62 - 68). WHOQOL-OLD mean score (SD) was 90.1 (8.3) out of 120. Factors that increased overall QoL were (Coefficient [95% Confidence Interval]): being male 2.35 (1.21 - 3.73), having an income of ≥$1 1.30 (-0.16 - 2.76) and paradoxically having more than 2 non-communicable diseases 0.69 (-0.76 - 2.14) in the past, present and future domain of QoL. Those that decreased QoL in the overall and various domains included: an increasing number of geriatric syndromes, depression, pre-frailty, frailty, malnutrition, and low physical function. Conclusion: Our findings suggest that financial stability contributed to good QoL while geriatric syndromes decreased QoL for OPWH. Integrating the screening and management of geriatric syndromes into HIV care has the potential to improve the overall QoL of OPWH.

Effectiveness and acceptance of group therapy as a mental health intervention for people living with HIV in Africa - a scoping literature review.

Mental health problems are highly prevalent among people living with HIV/AIDS (PLWHA), yet mental health care in African countries is scarce. There is growing interest in understanding the effect of group therapy delivery models and task-shifting to support mental health care in African settings. We conducted a scoping review following the PRISMA-ScR statement on group therapy in PLWHA in Africa. We searched PubMed/Medline, Embase, and Google Scholar for articles published before October 2023 on evidence for effectiveness and acceptance of group therapies in PLWHA, and evidence of task-shifting approaches. A narrative synthesis approach for data analysis was used. We included 17 studies, which comprised 26 different outcome measures across seven countries in sub-Sahara Africa. The majority (72%) of the assessed single outcomes demonstrated a positive impact of group therapy delivery models on outcome measures, particularly depression, alcohol use, overall functioning, and social support in sub-Sahara Africa. High acceptance was demonstrated by quantitative and qualitative approaches. Task shifting approaches generally were shown to be effective, cost-effective, and accepted, and may support burdened healthcare systems in rural settings. The current evidence, albeit scarce, supports the use of group therapy and task shifting in addressing mental health among PLWHA living in sub-Sahara Africa.

Anastrozole as a therapeutic option for gynecomastia in a person receiving antiretroviral therapy: Case report.

A middle-aged Caucasian man living with HIV, clinically stable (viral load <20 copies/mL) on injectable antiretroviral cabotegravir plus rilpivirine every 2 months presented with a 6-month history of bilateral enlargement of the breasts associated with pain. His hormonal profile was normal, and no other underlying cause was identified. He was diagnosed with idiopathic gynecomastia. Tamoxifen is an anti-oestrogen recommended for gynecomastia and has been described in people living with HIV but can potentially induce the activity of cytochrome P450 3A4 (CYP3A4), reducing rilpivirine concentrations, which consequently may cause virological failure and resistance. This is the same for other antiretroviral agents majorly induced by CYP3A4. To date, there have been no reported cases of using anastrozole as a treatment for gynecomastia in people living with HIV or of its co-administration with antiretroviral. We describe the use of an aromatase inhibitor instead of tamoxifen in a person living with HIV, diagnosed with gynecomastia.

Direct switch from an efavirenz-based regimen to intramuscular long-acting cabotegravir plus rilpivirine: A case report.

Switching from oral antiretroviral treatment to intramuscular (IM) cabotegravir (CAB) + rilpivirine (RPV) has an optional oral lead-in to ensure tolerability. The British HIV Association guidelines advise against directly switching from oral antiretroviral (ART) combinations containing strong/moderate cytochrome inducers like efavirenz (EFV) to IM CAB + RPV. EFV has a prolonged elimination half-life, leading to a residual induction of UGT1A1 and CYP3A4 after discontinuation. These enzymes are responsible for CAB and RPV metabolism and their induction might lead to sub-optimal concentrations of CAB and RPV, risking drug resistance. When switching from EFV to oral CAB + RPV, the ATLAS and ATLAS 2M studies showed reduced RPV concentrations but with maintained viral suppression during the oral lead-in and subsequent long-acting injectable (LAI) phases. Also, a recent pharmacokinetic modelling study indicated reduced RPV concentrations, without viral implication, when switching from EFV to IM CAB + RPV. However, there are limited real-world data on direct switching from EFV-based therapy to long-acting IM CAB + RPV. We describe a case where oral intake was impossible in a critical care scenario, switching from emitricitabine/tenofovir-DF (FTC/TDF) 200/245 mg + 600 mg EFV to IM CAB + RPV for treatment optimisation.

Barriers and facilitators of people living with HIV receiving optimal care for hypertension and diabetes in Tanzania: a qualitative study with healthcare professionals and people living with HIV.

BACKGROUND: People living with HIV (PLWH) are at a higher risk for developing diabetes and hypertension. Often services are separate for HIV and non-communicable diseases (NCDs), but how this impacts NCD care among PLWH is unknown. We aimed to understand the barriers and facilitators for prevention, early diagnosis and safe effective care for diabetes and hypertension among PLWH. METHODS: Semi-structured interviews (SSIs) were conducted with 10 healthcare professionals (HCPs) that care for PLWH, 10 HCPs that care for people with diabetes and hypertension and 16 PLWH with a comorbidity of diabetes and/or hypertension. Participants were recruited from two healthcare facilities in Dodoma, Tanzania and purposively sampled based on age and sex. Interviews were conducted in Swahili using pre-developed topic guides, audio recorded then translated verbatim into English. An inductive thematic analysis was conducted using The Framework Method. RESULTS: Three themes were found: organisational/healthcare system factors, individual factors and syndemic factors. Organisational/healthcare system factors comprised the only facilitators for prevention (education on lifestyle behaviours and counselling on adherence), but included the most barriers overall: fragmented services, no protocol for NCD screening and lack of access to diagnostic equipment were barriers for early diagnosis whereas the former plus lack of continuity of NCD care were barriers for safe effective care. Individual factors comprised four sub-themes, three of which were considered facilitators: HCPs' knowledge of NCDs for early diagnosis, self-monitoring of NCDs for safe effective care and HCPs' personal practice for both early diagnosis and safe effective care. HCPs' knowledge was simultaneously a barrier for prevention and PLWH knowledge was a barrier for prevention and safe effective care. Syndemic factors comprised three sub-themes; all were barriers for prevention, early diagnosis and/or safe effective care: poverty and mental health of PLWH and HIV stigma. CONCLUSIONS: Organisational/healthcare system, individual and syndemic factors were found to be interlinked with barriers and facilitators that contribute to the prevention, early diagnosis and safe effective care of diabetes and hypertension among PLWH in Tanzania; these findings can inform future initiatives for making small and large health system changes to improve the health of aging PLWH.

Upscaling cervical cancer screening and treatment for women living with HIV at a rural referral hospital in Tanzania: protocol of a before-and-after study exploring HPV testing and novel diagnostics.

BACKGROUND: Cervical cancer (CC) is nearly always caused by persistent human papillomavirus (HPV) infection. It is the most common cancer among women living with HIV (WLWH) and is the leading cause of cancer-related death in women in East Africa, with 10,241 new cases reported in Tanzania in 2020. In 2019, the World Health Organization (WHO) presented a global strategy for the elimination of CC as a public health problem, proposing targets to meet by 2030 for HPV vaccine coverage (90% of all 15-year-old girls), CC screening (70% of all women once at 35 and again at 45 years of age) and treatment delivery, to be scaled at national and subnational levels with a context-sensitive approach. This study aims to evaluate the upscaling of screening and treatment services at a rural referral hospital in Tanzania in order to address the second and third WHO targets. METHODS: This is an implementation study with a before-and-after design performed at St. Francis Referral Hospital (SFRH) in Ifakara (south-central Tanzania). CC screening and treatment services are integrated within the local HIV Care and Treatment Center (CTC). The standard of care, consisting of visualization of the cervix with acetic acid (VIA) and cryotherapy has been up-scaled with self-sampled HPV testing and also involved the introduction of mobile colposcopy, thermal ablation and loop electrosurgical excision procedure (LEEP). Participants are WLWH aged 18 to 65 years. Outcome measures included the percentage of women screened, HPV prevalence and genotype, and adherence to screening, treatment and follow-up plan. Additionally, we will explore the performance of novel diagnostic tests (QG-MPH®, Prevo-Check® and PT Monitor®), which share the features of being manageable and inexpensive, and thus a potential tool for effective triage in HPV high-prevalence cohorts. DISCUSSION: The study will provide relevant information about HPV prevalence and persistence, as well as reproductive and lifestyle indicators in a CC high-risk cohort of WLWH and about upscaling screening and treatment services at the level of a rural referral hospital in Tanzania. Furthermore, it will provide exploratory data on novel assays. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05256862, date of registration 25/02/2022. Retrospectively registered.

Stigma-directed services (Stig2Health) to improve 'linkage to care' for people living with HIV in rural Tanzania: study protocol for a nested pre-post implementation study within the Kilombero and Ulanga Antiretroviral Cohort.

Background: HIV-related stigma is a major barrier to the timely linkage and retention of patients in HIV care in sub-Saharan Africa, where most people living with HIV/AIDS reside. In this implementation study we aim to evaluate the effect of stigma-directed services on linkage to care and other health outcomes in newly diagnosed HIV-positive patients. Methods: In a nested project of the Kilombero and Ulanga Antiretroviral Cohort in rural Tanzania, we conduct a prospective observational pre-post study to assess the impact of a bundle of stigma-directed services for newly diagnosed HIV positive patients. Stigma-directed services, delivered by a lay person living with HIV, are i) post-test counseling, ii) post-test video-assisted teaching, iii) group support therapy and group health education, and iv) mobile health. Patients receiving stigma services (enrolled from 1 st February 2020 to 31 st August 2021) are compared to a historical control receiving the standard of care (enrolled from 1 st July 2017 to 1 st February 2019). The primary outcome is 'linkage to care'. Secondary endpoints are retention in care, viral suppression, death and clinical failure at 6-12 months (up to 31 st August 2022). Self-reported stigma and depression are assessed using the Berger Stigma scale and the PHQ-9 questionnaire, respectively. The sample size calculation was based on cohort data from 2018. Assuming a pre-intervention cohort of 511 newly diagnosed adults of whom 346 (68%) were in care and on antiretroviral treatment (ART) at 2 months, a 10% increase in linkage (from 70 to 80%), a two-sided type I error rate of 5%, and 90% power, 321 adults are required for the post-implementation group. Discussion: We expect that integration of stigma-directed services leads to an increase of proportions of patients in care and on ART. The findings will provide guidance on how to integrate stigma-directed services into routine care in rural sub-Saharan Africa.

Failure to return pillbox is a predictor of being lost to follow-up among people living with HIV on antiretroviral therapy in rural Tanzania.

OBJECTIVES: Pill count is used to assess drug adherence in people living with HIV (PLHIV). Carrying a pillbox is associated with fear of concealment and stigma and might indicate poor adherence and predict someone who will be lost to follow-up (LTFU). We therefore assessed the association between pillbox return and being LTFU in rural Tanzania. METHODS: This is a nested study of the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). We included PLHIV aged ≥ 18 years enrolled in KIULARCO between January 2013 and March 2019 with follow-up through January 2020, who were on antiretroviral treatment (ART) for ≥ 6 months. Baseline was defined as the latest ART initiation or KIULARCO enrolment. We determined the association between time-dependent failed pillbox return updated at every visit and LTFU using Kaplan-Meier estimation and Cox models. RESULTS: Among 2552 PLHIV included in the study, 1735 (68.0%) were female, 959 (40.3%) had a WHO stage III/IV and 1487 (66.4%) had a CD4 cell count < 350 cells/µL. The median age was 38.4 years [interquartile range (IQR): 31.7-46.2]. During a median follow-up of 33.1 months (IQR: 17.5-52.4), 909 (35.6%) participants were LTFU, 43 (1.7%) died and 194 (7.6%) had transferred to another clinic. The probability of being LTFU was higher among PLHIV with failed pillbox return than among those who returned their pillbox [30.0%, 95% confidence interval (CI): 26.8-33.2% vs. 19.4%, 95% CI: 17.4-21.6%, respectively, at 24 months (hazard ratio = 1.67, 95% CI: 1.46-1.90; p < 0.001)]. CONCLUSIONS: Failed pillbox return was associated with a higher risk of being LTFU and could be used as a simple tool to identify PLHIV for appropriate interventions to reduce their chance of being LTFU.

Prevalence, incidence and predictors of renal impairment in persons with HIV receiving protease-inhibitors in rural Tanzania.

OBJECTIVE: Ritonavir-boosted protease inhibitors (bPI) in people living with HIV (PLWH) have been associated with renal impairment. Limited data are available from rural sub-Saharan Africa. METHODS: Using data from the Kilombero and Ulanga Antiretroviral Cohort Study (KIULARCO) in rural Tanzania from 2005-01/2020, we assessed the prevalence of renal impairment (estimated glomerular filtration rate <60 mL/min/1.73m2) at the time of switch from first-line antiretroviral treatment (ART) to bPI-regimen and the incidence of renal impairment on bPI. We assessed risk factors for renal impairment using logistic and Cox regression models. RESULTS: Renal impairment was present in 52/687 PLWH (7.6%) at the switch to bPI. Among 556 participants with normal kidney function at switch, 41 (7.4%) developed renal impairment after a median time of 3.5 (IQR 1.6-5.1) years (incidence 22/1,000 person-years (95%CI 16.1-29.8)). Factors associated with renal impairment at switch were older age (adjusted odds ratio (aOR) 1.55 per 10 years; 95%CI 1.15-2.11), body mass index (BMI) <18.5 kg/m2 (aOR 2.80 versus ≥18kg/m2; 95%CI 1.28-6.14) and arterial hypertension (aOR 2.33; 95%CI 1.03-5.28). The risk of renal impairment was lower with increased duration of ART use (aOR 0.78 per one-year increase; 95%CI 0.67-0.91). The renal impairment incidence under bPI was associated with older age (adjusted hazard ratio 2.01 per 10 years; 95%CI 1.46-2.78). CONCLUSIONS: In PLWH in rural sub-Saharan Africa, prevalence and incidence of renal impairment among those who were switched from first-line to bPI-regimens were high. We found associations between renal impairment and older age, arterial hypertension, low BMI and time on ART.

"Linkage to care" among people living with HIV - definition in the era of "universal test and treat" in a sub-Sahara African setting.

BACKGROUND: Prompt linkage to human immunodeficiency virus (HIV) care after diagnosis is of utmost importance for individual health and reduction of HIV transmission. Different definitions for "linkage to care" have challenged comparisons as a public health marker. Its meaning in the era of "universal test and treat" has transformed in all settings, but is most relevant in sub-Sahara Africa, where the burden of new HIV infection is still highest. METHODS: For this narrative review on "linkage to care" definitions with a focus on sub-Saharan Africa, we searched PubMed/Medline between September and December 2020, restricted to the period 2000­2020 using Boolean operators: "HIV" AND ("linkage to care" OR "engagement in care") and screened for institutional definitions of "linkage to care". Additionally, as one example of a rural sub-Saharan African setting, we analysed linkage steps within the Chronic Diseases Clinic Ifakara (CDCI) and its associated Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) in rural Tanzania between 1 January 2017 and 31 March 2019. RESULTS: We analysed 81 articles that included "linkage to care" within different study settings and HIV organisations. Major differences in defining "linkage to care" exist, according to setting and location, patient populations and the timing of steps within the linkage process. We identified 16 different numerators and 10 denominators used to define linkage with time periods ranging from "same day as diagnosis" up to 12 months after diagnosis among 34 original articles from sub-Saharan Africa. At the CDCI, 1149/1671 (69%) newly diagnosed individuals were enrolled into care after diagnosis. Three months after enrolment into care, 94%, 86%, 85% and 71% of enrolled patients had a laboratory evaluation, a clinical evaluation, were initiated on treatment and had a first clinical follow-up visit after initiation of treatment, respectively. DUSCUSSION: To address the inconsistency in defining "linkage to care" and in order to guarantee the comparability of "linkage to care" in the sub-Saharan Africa region, we support the definition from the European region with some adaptions. We suggest a priority list of care indicators if more than one care indicator is available for successful "linkage to care" in the era of "universal test and treat" for sub-Sahara Africa.

The coArtHA trial-identifying the most effective treatment strategies to control arterial hypertension in sub-Saharan Africa: study protocol for a randomized controlled trial.

BACKGROUND: Arterial hypertension is the most prevalent risk factor for cardiovascular disease in sub-Saharan Africa. Only a few and mostly small randomized trials have studied antihypertensive treatments in people of African descent living in sub-Saharan Africa. METHODS: In this open-label, three-arm, parallel randomized controlled trial conducted at two rural hospitals in Lesotho and Tanzania, we compare the efficacy and cost-effectiveness of three antihypertensive treatment strategies among participants aged ≥ 18 years. The study includes patients with untreated uncomplicated arterial hypertension diagnosed by a standardized office blood pressure ≥ 140/90 mmHg. The trial encompasses a superiority comparison between a triple low-dose antihypertensive drug combination versus the current standard of care (monotherapy followed by dual treatment), as well as a non-inferiority comparison for a dual drug combination versus standard of care with optional dose titration after 4 and 8 weeks for participants not reaching the target blood pressure. The sample size is 1268 participants with parallel allocation and a randomization ratio of 2:1:2 for the dual, triple and control arms, respectively. The primary endpoint is the proportion of participants reaching a target blood pressure at 12 weeks of ≤ 130/80 mmHg and ≤ 140/90 mmHg among those aged < 65 years and ≥ 65 years, respectively. Clinical manifestations of end-organ damage and cost-effectiveness at 6 months are secondary endpoints. DISCUSSION: This trial will help to identify the most effective and cost-effective treatment strategies for uncomplicated arterial hypertension among people of African descent living in rural sub-Saharan Africa and inform future clinical guidelines on antihypertensive management in the region. TRIAL REGISTRATION: Clinicaltrials.gov NCT04129840 . Registered on 17 October 2019 ( https://www.clinicaltrials.gov/ ).

Maternal and fetal risk factors for stillbirth in Northern Tanzania: A registry-based retrospective cohort study.

BACKGROUND: Stillbirth is a major cause of perinatal mortality and occurs disproportionately in developing countries including Tanzania. However, there is scant information regarding the predictors of this condition in Tanzania. This study aimed to determine maternal and fetal risk factors for stilbirth in northen Tanzania. METHODOLOGY: A retrospective cohort study was performed using maternally-linked data from the Kilimanjaro Christian Medical Centre birth registry. A total of 47681 women who had singleton delivery at KCMC between 2000 and 2014 were analyzed. Women with multiple gestations were excluded. Descriptive statistics were summarized using proportions and frequency. Chi-square test was used to determine risk factors for stillbirth in bivariate analysis. A multivariable regression model was used to estimate adjusted odds ratios (AOR) with 95% confidence intervals for maternal and fetal factors associated with stillbirth. A p-value of less than 0.05 was considered statistically significant. RESULTS: The frequency of stillbirth was 3.5%. Pre-eclampsia (AOR 3.99; 95% CI: 3.31-4.81) and placental abruption (AOR 22.62; 95% CI: 15.41-33.19) were the strongest maternal risk factors associated with still birth. While non-cephalic presentation (AOR 6.05; 95% CI: 4.77-7.66) and low birth weight (AOR 9.66; 95%CI: 8.66-10.77) were the fetal factors with the greatest impact on stillbirth. CONCLUSION: The rate of stillbirth in our study was consistent with past studies of developing countries. Numerous maternal and fetal factors risk factors were identified. Early identification of at risk pregnancies and appropriate intervention may help to reduce the occurrence of stillbirth.

Frequency, Risk Factors, and Adverse Fetomaternal Outcomes of Placenta Previa in Northern Tanzania.

Background and Objective. Placenta previa (PP) is a potential risk factor for obstetric hemorrhage, which is a major cause of fetomaternal morbidity and mortality in developing countries. This study aimed to determine frequency, risk factors, and adverse fetomaternal outcomes of placenta previa in Northern Tanzania. Methodology. A retrospective cohort study was conducted using maternally-linked data from Kilimanjaro Christian Medical Centre birth registry spanning 2000 to 2015. All women who gave birth to singleton infants were studied. Adjusted odds ratios (ORs) with 95% confidence intervals for risk factors and adverse fetomaternal outcomes associated with PP were estimated in multivariable logistic regression models. Result. A total of 47,686 singleton deliveries were analyzed. Of these, the frequency of PP was 0.6%. Notable significant risk factors for PP included gynecological diseases, alcohol consumption during pregnancy, malpresentation, and gravidity ≥5. Adverse maternal outcomes were postpartum haemorrhage, antepartum haemorrhage, and Caesarean delivery. PP increased odds of fetal Malpresentation and early neonatal death. Conclusion. The prevalence of PP was comparable to that found in past research. Multiple independent risk factors were identified. PP was found to have associations with several adverse fetomaternal outcomes. Early identification of women at risk of PP may help clinicians prevent such complications.