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BackgroundCryptococcal infection is a common opportunistic infection among severely immunosuppressed HIV patients and is associated with high mortality. Positive cryptococcal antigenemia is an independent predictor of cryptococcal meningitis and death in patients with severe immunosuppression. We evaluated the prevalence and factors associated with cryptococcal antigenemia among patients with CD4 counts of 100 cells/mm3 or less in Mulago Hospital, Kampala, Uganda. Screening of a targeted group of HIV patients may enable early detection of cryptococcal infection and intervention before initiating antiretroviral therapy. Factors associated with cryptococcal antigenemia may be used subsequently in resource‐limited settings in screening for cryptococcal infection, and this data may also inform policy for HIV care.MethodsIn this cross‐sectional study, HIV‐infected patients aged 18 years and older with CD4 counts of up to 100 cells/mm3 were enrolled between December 2009 and March 2010. Data on socio‐demographics, physical examinations and laboratory tests were collected. Factors associated with cryptococcal antigenemia were analyzed using multiple logistic regression.ResultsWe enrolled 367 participants and the median CD4 count was 23 (IQR 9‐51) cells/mm3. Sixty‐nine (19%) of the 367 participants had cryptococcal antigenemia. Twenty‐four patients (6.5%) had cryptococcal meningitis on cerebrospinal fluid analysis and three had isolated cryptococcal antigenemia. Factors associated with cryptococcal antigenemia included: low body mass index of 15.4 kg/m2 or less (adjusted odds ratio, AOR = 0.5; 95% CI 0.3‐1.0), a CD4+ T cell count of less than 50 cells/mm3 (AOR = 2.7; 95% CI1.2‐6.1), neck pain (AOR = 2.3; 95% CI 1.2‐4.6), recent diagnosis of HIV infection (AOR = 1.9; 95% CI 1.1‐3.6), and meningeal signs (AOR = 7.9; 95% CI 2.9‐22.1). However, at sub‐analysis of asymptomatic patients, absence of neck pain (AOR = 0.5), photophobia (AOR = 0.5) and meningeal signs (AOR = 0.1) were protective against cryptococcal infection.ConclusionsCryptococcal antigenemia is common among severely immunosuppressed HIV patients in Mulago Hospital, Kampala, Uganda. Independent predictors of positive serum cryptococcal antigenemia were CD4+ T cell counts of less than 50 cells/mm, low body mass index, neck pain, signs of meningeal irritation, and a recent diagnosis of HIV infection. Routine screening of this category of patients may detect cryptococcosis, and hence provide an opportunity for early intervention. Absence of neck pain, photophobia and meningeal signs were protective against cryptococcal infection compared with symptomatic patients.

BackgroundWith widespread use of antiretroviral therapy (ART) and prolonged survival of HIV‐infected children, toxicities like lipodystrophy are becoming more evident. Little is known about lipodystrophy in children in Uganda yet there is increased use of ART. The aim of this study was to determine the prevalence and factors associated with fat redistribution and metabolic abnormalities among HIV‐infected children on highly active antiretroviral therapy (HAART) in Uganda.MethodsA cross‐sectional study of 364 HIV positive children aged between 2 and 18 years on ART were enrolled after consent and assent as appropriate. Sociodemographic, clinical and immunological data were collected and recorded in a questionnaire. Fat redistribution was assessed clinically for physical findings of lipohypertrophy and lipoatrophy. A fasting blood sample was taken for lipid profile and blood glucose analysis. Lipodystrophy was defined as presence of abnormal fat redistribution or metabolic abnormalities or both. The proportion of children with fat redistribution and metabolic abnormalities was calculated. We conducted multivariate analysis for factors associated with lipodystrophy among children with lipodystrophic features and those without.ResultsThe median age of the participants was eight years (range 2 to 18), with 43% of these aged ≥10 years and a male to female ratio of 1.1:1. Majority (65%) had advanced HIV (WHO Stage III/IV) at ART initiation with a mean duration on ART of 3.8 years (±1.2). The prevalence of fat redistribution and hyperlipidemia was 27.0% and 34.0%, respectively. None of the children had hyperglycaemia. Among the children with hyperlipidemia, 16.8% exhibited hypercholesterolemia and 83% had hypertriglyceridemia. Only 29% of children with fat redistribution had hyperlipidemia. We found significant association between fat redistribution and Tanner stages 2 to 5 OR=2.3 (95%CI 1.3 to 3.8), age≥5 years OR=3.9 (95%CI 1.5 to 9.9) and d4T exposure OR=3.4 (95%CI 2.0 to 5.8). A Tanner stage 2 to 5 was independently associated with hyperlipidemia. No significant association was observed with HIV clinical stage and any of the anthropometric measurements.ConclusionThe prevalence of lipodystrophy is high among HIV‐infected children on ART with a likelihood of developing fat redistribution and metabolic abnormalities increased during puberty.

IntroductionHIV/ AIDS clinics in resource limited settings (RLS) face increasing numbers of patients and workforce shortage [1, 2]. To address these challenges, efficient models of care like pharmacy only visits (POV) and nurse only visits (NOV) are recommended [3]. The Makerere University Joint AIDS Program (MJAP), a PEPFAR funded program providing care to over 42,000 HIV infected adults has implemented the POV model since 2009. In this model, stable patients on antiretroviral therapy (ART) with adherence to ART >95% and Karnofsky score >90% are reviewed by a doctor every four months but visit pharmacy for ART re‐fills every two months. A study conducted in August 2011 showed low retention on the POV program with symptomatic diseases, pending CD4 count, complete blood count results, and poor adherence to ART as the major reasons for the non‐retention in the POV program. To improve retention on POV, the TAT (Turnaround Time) for laboratory results (the main reason for non‐retention in the previous study) was reduced from one month to one week. In August 2012, the study was repeated to assess the effect of reducing TAT on improving retention one year after patients were placed on POV.Materials and MethodsA cohort analysis of data from patients in August 2011 and in August 2012 on POV was done. We compared retention of POV before and after reducing the TAT for laboratory results.ResultsRetention on POV was 12.0% (95% CI 9.50–14.7) among 619 patients in 2011, (70% Females), mean age was 33 years, Standard Deviation (SD) 8.5 compared to 11.1% (95% CI 9.15–13.4) among 888 patients (70% Females), mean age 38.3 years, SD 8.9 in 2012 (p=0.59). The main reasons for non‐retention on the POV program in 2012 were poor adherence to ART (23%) and missed clinic appointments (14%).ConclusionsReducing TAT for laboratory test results did not improve retention of stable HIV‐infected adults on POV in our clinic. Strategies for improving adherence to ART and keeping clinic appointments need to be employed to balance workload and management of patients without compromising quality of care, patients' clinical, immunological and adherence outcome.

AbstractIntroductionGeographic and transportation barriers are associated with poorer HIV‐related health outcomes in sub‐Saharan Africa, but data on the impact of these barriers on prevention interventions are limited. We estimated the association between distance to clinic and other transportation‐related barriers on pre‐exposure prophylaxis (PrEP) uptake and initial clinic visit attendance in a rural community in southwestern Uganda enrolled in the ongoing SEARCH study (NCT01864603).MethodsCommunity‐wide HIV testing was conducted and offered to adult (≥15 years) participants in Ruhoko. Participants were eligible for PrEP based on an empiric risk score, having an HIV‐discordant partner, or self‐referral at either the community health campaign or during home‐based testing from March to April 2017. We collected data from PrEP‐eligible households on GPS‐measured distance to clinic, walking time to clinic and road difficulty. A sample of participants was also asked to identify their primary barriers to PrEP use with a semi‐quantitative questionnaire. We used multivariable logistic regression to evaluate the association between transportation barriers and (1) PrEP uptake among PrEP‐eligible individuals and (2) four‐week clinic visit attendance among PrEP initiators.ResultsOf the 701 PrEP‐eligible participants, 272 (39%) started PrEP within four weeks; of these, 45 (17%) were retained at four weeks. Participants with a distance to clinic of ≥2 km were less likely to start PrEP (aOR 0.34; 95% CI 0.15 to 0.79, p = 0.012) and less likely to be retained on PrEP once initiated (aOR 0.29; 95% CI 0.10 to 0.84; p = 0.024). Participants who were deemed eligible during home‐based testing and did not have the option of same‐day PrEP start were also substantially less likely to initiate PrEP (aOR 0.16, 95% CI 0.07 to 0.37, p < 0.001). Of participants asked to name barriers to PrEP use (N = 98), the most frequently cited were "needing to take PrEP every day" (N = 18) and "low/no risk of getting HIV" (N = 18). Transportation‐related barriers, including "clinic is too far away" (N = 6) and "travel away from home" (N = 4) were also reported.ConclusionsDistance to clinic is a significant predictor of PrEP uptake and four‐week follow‐up visit attendance in a community in rural Uganda. Interventions that address geographic and transportation barriers may improve PrEP uptake and retention in sub‐Saharan Africa.

AbstractIntroduction: Multi‐disease community health campaigns can be effective for population‐wide HIV testing in a research setting (SEARCH: NCT01864603). We sought to evaluate feasibility and uptake of a community‐led health campaign (CLHC) planned and implemented by village leaders and local clinic workers in Uganda.Methods: Over five months in 2014, locally elected village leaders and Ministry of Health (MoH) clinic staff in a rural parish in Uganda planned a census followed by a CLHC, after training by two SEARCH trial consultants and by leaders from a neighbouring parish that had previously participated in a SEARCH health campaign. We defined feasibility as: (1) elected leaders' participation in training and implementation of pre‐campaign census and mobilization activities; (2) implementation of all campaign activities by MoH‐funded, local clinic staff; and (3) community participation in the campaign, including point‐of‐care screening for HIV, malaria, hypertension and diabetes, and same‐day referral for male circumcision and family planning (FP). Costing of all salaries and supplies was conducted.Results: Elected leaders from all eight villages in the parish participated in CLHC training. They and local clinic staff met monthly to select and plan CLHC services. Village leaders then leveraged existing volunteer health teams to perform a door‐to‐door census, enumerating 5,202 parish residents over 2 weeks. 2,753 (53%) residents participated in the 6‐day CLHC. Of 1,584 adult participants, 1,474 (93%) tested for HIV: 105/1,474 (7.1%) tested HIV positive. 27% (751/2,753) of participants reported fever and underwent malaria rapid diagnostic testing: 5.3% (40/751) tested positive. Among adults screened, 19% (271/1,452) were hypertensive, and 3% (18/637) had a random blood sugar >11.1 mmol/L. Of 805 men and boys (>10 years), 91 (11%) accepted same‐day clinic referral and underwent medical circumcision. Of 900 women offered same‐day long‐term FP referrals, 25 accepted. The CLHC cost, including census, mobilization and testing services, was $23,597 ($8.57/participant).Conclusions: Elected village leaders successfully planned and conducted a 6‐day multi‐disease health campaign with service provision by local clinic staff that reached over half of a rural Ugandan community. These data suggest it is feasible for local leaders and clinics to adopt a multi‐disease health campaign approach to scale‐up HIV testing in rural Africa.

AbstractIntroductionPerson‐centred HIV prevention delivery models that offer structured choices in product, testing and visit location may increase coverage. However, data are lacking on the actual uptake of choices among persons at risk of HIV in southern Africa. In an ongoing randomized study (SEARCH; NCT04810650) in rural East Africa, we evaluated the uptake of choices made when offered in a person‐centred, dynamic choice model for HIV prevention.MethodsUsing the PRECEDE framework, we developed a persont‐centred, Dynamic Choice HIV Prevention (DCP) intervention for persons at risk of HIV in three settings in rural Kenya and Uganda: antenatal clinic (ANC), outpatient department (OPD) and in the community. Components include: provider training on product choice (predisposing); flexibility and responsiveness to client desires and choices (pre‐exposure prophylaxis [PrEP]/post‐exposure prophylaxis [PEP], clinic vs. off‐site visits and self‐ or clinician‐based HIV testing) (enabling); and client and staff feedback (reinforcing). All clients received a structured assessment of barriers with personalized plans to address them, mobile phone access to clinicians (24 hours/7 days/week) and integrated reproductive health services. In this interim analysis, we describe the uptake of choices of product, location and testing during the first 24 weeks of follow‐up (April 2021−March 2022).ResultsA total of 612 (203 ANC, 197 OPD and 212 community) participants were randomized to the person‐centred DCP intervention. We delivered the DCP intervention in all three settings with diverse populations: ANC: 39% pregnant; median age: 24 years; OPD: 39% male, median age 27 years; and community: 42% male, median age: 29 years. Baseline choice of PrEP was highest in ANC (98%) vs. OPD (84%) and community (40%); whereas the proportion of adults selecting PEP was higher in the community (46%) vs. OPD (8%) and ANC (1%). Personal preference for off‐site visits increased over time (65% at week 24 vs. 35% at baseline). Interest in alternative HIV testing modalities grew over time (38% baseline self‐testing vs. 58% at week 24).ConclusionsA person‐centred model incorporating structured choice in biomedical prevention and care delivery options in settings with demographically diverse groups, in rural Kenya and Uganda, was responsive to varying personal preferences over time in HIV prevention programmes.

AbstractIntroductionAntiretroviral‐based HIV prevention, including pre‐exposure prophylaxis (PrEP), is expanding in generalized epidemic settings, but additional prevention options are needed for individuals with periodic, high‐risk sexual exposures. Non‐occupational post‐exposure prophylaxis (PEP) is recommended in global guidelines. However, in Africa, awareness of and access to PEP for sexual exposures are limited. We assessed feasibility, acceptability, uptake and adherence in a pilot study of a patient‐centred PEP programme with options for facility‐ or community‐based service delivery.MethodsAfter population‐level HIV testing with universal access to PrEP for persons at elevated HIV risk (SEARCH Trial:NCT01864603), we conducted a pilot PEP study in five rural communities in Kenya and Uganda between December 2018 and May 2019. We assessed barriers to PEP in the population and implemented an intervention to address these barriers, building on existing in‐country PEP protocols. We used community leaders for sensitization. Test kits and medications were acquired through the Ministry of Health supply chain and healthcare providers based at the Ministry of Health clinics were trained on PEP delivery. Additional intervention components were (a)PEP availability seven days/week, (b)PEP hotline staffed by providers and (c)option for out‐of‐facility medication delivery. We assessed implementation using the Proctor framework and measured seroconversions via repeat HIV testing. Successful "PEP completion" was defined as self‐reported adherence over four weeks of therapy with post‐PEP HIV testing.ResultsCommunity leaders were able to sensitize and mobilize for PEP. The Ministry of Health supplied test kits and PEP medications; after training, healthcare providers delivered the 28‐day regimen with high completion rates. Among 124 persons who sought PEP, 66% were female, 24% were ≤25 years and 42% were fisherfolk. Of these, 20% reported exposure with a serodifferent partner, 72% with a new or existing relationship and 7% from transactional sex. 12% of all visits were conducted at out‐of‐facility community‐based sites; 35% of participants had ≥1 out‐of‐facility visit. No serious adverse events were reported. Overall, 85% met the definition of PEP completion. There were no HIV seroconversions.ConclusionsAmong individuals with elevated‐risk exposures in rural East African communities, patient‐centred PEP was feasible, acceptable and provides a promising addition to the current prevention toolkit.

AbstractIntroductionThere are significant knowledge gaps concerning complex forms of mobility emergent in sub‐Saharan Africa, their relationship to sexual behaviours, HIV transmission, and how sex modifies these associations. This study, within an ongoing test‐and‐treat trial (SEARCH, NCT01864603), sought to measure effects of diverse metrics of mobility on behaviours, with attention to gender.MethodsCross‐sectional data were collected in 2016 from 1919 adults in 12 communities in Kenya and Uganda, to examine mobility (labour/non‐labour‐related travel), migration (changes of residence over geopolitical boundaries) and their associations with sexual behaviours (concurrent/higher risk partnerships), by region and sex. Multilevel mixed‐effects logistic regression models, stratified by sex and adjusted for clustering by community, were fitted to examine associations of mobility with higher‐risk behaviours, in past 2 years/past 6 months, controlling for key covariates.ResultsThe population was 45.8% male and 52.4% female, with mean age 38.7 (median 37, IQR: 17); 11.2% had migrated in the past 2 years. Migration varied by region (14.4% in Kenya, 11.5% in southwestern and 1.7% in eastern and Uganda) and sex (13.6% of men and 9.2% of women). Ten per cent reported labour‐related travel and 45.9% non‐labour‐related travel in past 6 months—and varied by region and sex: labour‐related mobility was more common in men (18.5%) than women (2.9%); non‐labour‐related mobility was more common in women (57.1%) than men (32.6%). In 2015 to 2016, 24.6% of men and 6.6% of women had concurrent sexual partnerships; in past 6 months, 21.6% of men and 5.4% of women had concurrent partnerships. Concurrency in 2015 to 2016 was more strongly associated with migration in women [aRR = 2.0, 95% CI(1.1 to 3.7)] than men [aRR = 1.5, 95% CI(1.0 to 2.2)]. Concurrency in past 6 months was more strongly associated with labour‐related mobility in women [aRR = 2.9, 95% CI(1.0 to 8.0)] than men [aRR = 1.8, 95% CI(1.2 to 2.5)], but with non‐labour‐related mobility in men [aRR = 2.2, 95% CI(1.5 to 3.4)].ConclusionsIn rural eastern Africa, both longer‐distance/permanent, and localized/shorter‐term forms of mobility are associated with higher‐risk behaviours, and are highly gendered: the HIV risks associated with mobility are more pronounced for women. Gender‐specific interventions among mobile populations are needed to combat HIV in the region.

AbstractIntroductionThe Streamlined Antiretroviral Therapy Initiation Strategy (START‐ART) study found that a theory‐based intervention using opinion leaders to inform and coach health care providers about the risks of treatment delay, provision of point of care (POC) CD4 testing machines (PIMA) and reputational incentives, led to rapid rise in ART initiation. We used qualitative research methods to explore mechanisms of provider behaviour change.MethodsWe conducted in‐depth interviews (IDIs) with 24 health care providers and nine study staff to understand perceptions, attitudes and the context of changes in ART initiation practices. Analyses were informed by the Theoretical Domains Framework.ResultsRapid dissemination of new practices was enabled in the environmental context of an existing relationship based on communication, implementation and accountability between Makerere University Joint AIDS Program (MJAP), a Ugandan University‐affiliated organization that provided technical oversight for HIV service delivery at the health facilities where the intervention was implemented, and a network of health facilities operated by the Uganda Ministry of Health. Coaching carried out by field coordinators from MJAP strengthened influence and informal accountability for carrying out the intervention. Frontline health workers held a pre‐existing strong sense of professional identity. They were proud of attainment of new knowledge and skills and gratified by providing what they perceived to be higher quality care. Peer counsellors, who were not explicitly targeted in the intervention design, effectively substituted some functions of health care providers; as role models for successful ART uptake, they played a crucial role in creating demand for rapid ART initiation through interactions with patients. Point of care (POC) CD4 testing enabled immediate action and relieved providers from frustrations of lost or delayed laboratory results, and led to higher patient satisfaction (due to reduced costs because of ability to initiate ART right away, requiring fewer return trips to clinic).ConclusionsQualitative data revealed that a multicomponent intervention to change provider behaviour succeeded in the context of strong institutional and individual relationships between a University‐affiliated organization, government facilities, and peer health workers (who acted as a crucial link between stakeholders) and the community. Fostering stable institutional relationships between institutional actors (non‐governmental organization (NGOs) and ministry‐operated facilities) as well as between facilities and the community (through peer health workers) can enhance uptake of innovations targeting the HIV cascade in similar clinical settings.

IntroductionThe Streamlined Antiretroviral Therapy Initiation Strategy (START-ART) study found that a theory-based intervention using opinion leaders to inform and coach health care providers about the risks of treatment delay, provision of point of care (POC) CD4 testing machines (PIMA) and reputational incentives, led to rapid rise in ART initiation. We used qualitative research methods to explore mechanisms of provider behaviour change.MethodsWe conducted in-depth interviews (IDIs) with 24 health care providers and nine study staff to understand perceptions, attitudes and the context of changes in ART initiation practices. Analyses were informed by the Theoretical Domains Framework.ResultsRapid dissemination of new practices was enabled in the environmental context of an existing relationship based on communication, implementation and accountability between Makerere University Joint AIDS Program (MJAP), a Ugandan University-affiliated organization that provided technical oversight for HIV service delivery at the health facilities where the intervention was implemented, and a network of health facilities operated by the Uganda Ministry of Health. Coaching carried out by field coordinators from MJAP strengthened influence and informal accountability for carrying out the intervention. Frontline health workers held a pre-existing strong sense of professional identity. They were proud of attainment of new knowledge and skills and gratified by providing what they perceived to be higher quality care. Peer counsellors, who were not explicitly targeted in the intervention design, effectively substituted some functions of health care providers; as role models for successful ART uptake, they played a crucial role in creating demand for rapid ART initiation through interactions with patients. Point of care (POC) CD4 testing enabled immediate action and relieved providers from frustrations of lost or delayed laboratory results, and led to higher patient satisfaction (due to reduced costs because of ability to initiate ART right away, requiring fewer return trips to clinic).ConclusionsQualitative data revealed that a multicomponent intervention to change provider behaviour succeeded in the context of strong institutional and individual relationships between a University-affiliated organization, government facilities, and peer health workers (who acted as a crucial link between stakeholders) and the community. Fostering stable institutional relationships between institutional actors (non-governmental organization (NGOs) and ministry-operated facilities) as well as between facilities and the community (through peer health workers) can enhance uptake of innovations targeting the HIV cascade in similar clinical settings.

AbstractIntroductionThe concept of "therapeutic citizenship" has drawn attention to ways in which public testimony, the "story‐telling in the public sphere" undertaken by people living with HIV (PLHIV), has shaped the global response to the epidemic. This paper presents qualitative findings from two large studies in eastern Africa that reveal how the advent of population‐based HIV testing campaigns and efforts to accelerate antiretroviral "treatment for all" has precipitated a rapidly expanding therapeutic citizenship "project," or social movement. The title of this paper refers to Goffman's original conceptualization of stigma as a social process through which a person's identity is rendered "spoiled."MethodsData were derived from qualitative studies embedded within two clinical trials, Sustainable East African Research in Community Health (SEARCH) (NCT# 01864603) in Kenya and Uganda, and START‐ART (NCT# 01810289) in Uganda, which aimed to offer insights into the pathways through which outcomes across the HIV care continuum can be achieved by interventions deployed in the studies, any unanticipated consequences, and factors that influenced implementation. Qualitative in‐depth semi‐structured interviews were conducted among cohorts of adults in 2014 through 2015; across both studies and time periods, 217 interviews were conducted with 166 individuals. Theoretically informed, team‐based analytic approaches were used for the analyses.ResultsNarratives from PLHIV, who have not always been conceptualized as actors but rather usually as targets of HIV interventions, revealed strongly emergent themes related to these individuals' use of HIV biomedical resources and discourses to fashion a new, empowered subjecthood. Experiencing the benefits of antiretroviral therapy (ART) emboldens many individuals to transform their "spoiled" identities to attain new, valorized identities as "advocates for ART" in their communities. We propose that the personal revelation of what some refer to as the "gospel of ARVs," the telling of personal stories about HIV in the public sphere and actions to accompany other PLHIV on their journey into care, is driven by its power to redeem the "spoiled identity:" it permits PLHIV to overcome self‐stigma and regain full personhood within their communities.ConclusionsPLHIV are playing an unanticipated but vital role in the successful implementation of HIV care cascade interventions.