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Background HIV disclosure is vital in HIV management. Community Health Workers (CHW) were reported to support partner disclosure among HIV affected heterosexual partners with disclosure difficulties. However, time to disclosure attributed to use of CHW led disclosure support mechanism was not documented. This study compared the incidence of sexual partner disclosure among adults living with HIV (ALHIV) with CHW support and those without in the greater Luwero region, Uganda. Methods We conducted a quasi-experimental study with two arms allocated by geographically determined clusters and adjusted for between-group differences; among ALHIV in the greater Luwero region of Uganda who had never disclosed to their current primary sexual partners. We allocated study clusters to either a CHW-led intervention or control arm. In both arms, we consecutively recruited participants; those in the intervention arm received CHW disclosure support in addition to routine care. The overall follow-up was six months, and the primary outcome was disclosure to the partner. We used survival analysis with proportional hazard ratios to determine the time to partner disclosure in both arms. Results A total of 245 participants were enrolled, and 230 (93.9%) completed the study; of these, 112 (48.7%) were in the intervention and 118 (51.3%) in the control arm. The mean age was 31 ± 8 years with a range of 18 to 55 years; the majority were females, 176 (76.5%). The cumulative incidence of disclosure was higher in the intervention arm, 8.76 [95% CI: 7.20–10.67] per 1,000 person-days versus 5.15 [95%CI: 4.85–6.48] per 1,000 person-days in the control arm, log-rank test, X2 = 12.93, P Male gender, aHR = 1.82, tertiary education, aHR = 1.51, and relationship duration of > six months, aHR = 1.19 predicted disclosure. Prior disclosure to a relative, aHR = 0.55, and having more than one sexual partner in the past three months, aHR = 0.74, predicted non-disclosure. Conclusion CHW-led support mechanism increased the rate of sexual partner disclosure among ALHIV with disclosure difficulties. Therefore, to achieve the global targets of ending HIV, near location CHW-led disclosure support mechanism may be used to hasten HIV disclosure in rural settings.

Background HIV status disclosure among sexual partners is vital in HIV management. Community health workers (CHW) support HIV disclosure among adults living with HIV (ALHIV) in sexual relationships with disclosure difficulties. However, experiences and challenges of using CHW-led disclosure support mechanism were not documented. This study explored experiences and challenges involved in using CHW-led disclosure support mechanism among ALHIV in heterosexual relationships in the rural Uganda. Methods This was a phenomenological qualitative study involving in-depth interviews among CHWs and ALHIV with HIV disclosure difficulties to sexual partners in greater Luwero region, Uganda. We conducted 27 interviews among purposively selected CHWs and participants who had participated in the CHW-led disclosure support mechanism. Interviews were conducted until saturation was reached; and analysis was done using inductive and deductive content analysis in Atlas. Results All respondents viewed HIV disclosure as an important strategy in HIV management. Provision of adequate counseling and support to those intending to disclose was instrumental for successful disclosure. However, fear of the negative disclosure outcomes was viewed as a barrier to disclosure. The CHWs were viewed as having an added advantage in supporting disclosure as opposed to the routine disclosure counseling. However, HIV disclosure using CHW-led support mechanism would be limited by possible bleach of client’s confidentiality. Therefore, respondents thought that appropriate selection of CHWs would improve their trust in the community. Additionally, providing CHWs with adequate training and facilitation during the disclosure support mechanism was viewed to improve their work. Conclusion Community health workers were viewed as being more supportive in HIV disclosure among ALHIV with disclosure difficulties to sexual partners compared to routine facility based disclosure counseling. Therefore, near location CHW-led disclosure mechanism was acceptable and useful in supporting HIV disclosure among HIV-affected sexual partners in rural settings.

Background Transfusion-transmitted infections (TTIs) are a global health challenge. One new approach to reduce TTIs is the use of pathogen reduction technology (PRT). In vitro, Mirasol PRT reduces the infectious load in whole blood (WB) by at least 99%. However, there are limited in vivo data on the safety and efficacy of Mirasol PRT. The objective of the Mirasol Evaluation of Reduction in Infections Trial (MERIT) is to investigate whether Mirasol PRT of WB can prevent seven targeted TTIs (malaria, bacteria, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, hepatitis E virus, and human herpesvirus 8). Methods MERIT is a randomized, double-blinded, controlled clinical trial. Recruitment started in November 2019 and is expected to end in 2024. Consenting participants who require transfusion as medically indicated at three hospitals in Kampala, Uganda, will be randomized to receive either Mirasol-treated WB (n = 1000) or standard WB (n = 1000). TTI testing will be performed on donor units and recipients (pre-transfusion and day 2, day 7, week 4, and week 10 after transfusion). The primary endpoint is the cumulative incidence of one or more targeted TTIs from the Mirasol-treated WB vs. standard WB in a previously negative recipient for the specific TTI that is also detected in the donor unit. Log-binomial regression models will be used to estimate the relative risk reduction of a TTI by 10 weeks associated with Mirasol PRT. The clinical effectiveness of Mirasol WB compared to standard WB products in recipients will also be evaluated. Discussion Screening infrastructure for TTIs in low-resource settings has gaps, even for major TTIs. PRT presents a fast, potentially cost-effective, and easy-to-use technology to improve blood safety. MERIT is the largest clinical trial designed to evaluate the use of Mirasol PRT for WB. In addition, this trial will provide data on TTIs in Uganda. Trial registration Mirasol Evaluation of Reduction in Infections Trial (MERIT) NCT03737669. Registered on 9 November 2018

Background Viral load (VL) testing is key in monitoring adherence to antiretroviral therapy (ART) and documenting HIV treatment response. As per HIV treatment guidelines in Uganda, the first VL test is recommended 6 months after initiation of ART. Undetectable VL (uVL) at ART initiation may be helpful in detecting elite controllers in the absence of previous ART use. We investigated viral suppression at ART initiation among a cohort of HIV-positive pregnant women enrolled in the Friends for Life Circles (FLC) for Option B+ randomized controlled trial (RCT). Methods Pregnant women ≥ 18 years of age testing positive for HIV at their first antenatal care visit and starting on ART Option B+ as per the National PMTCT Program guidelines were enrolled into the FLC for Option B+ RCT in urban Kampala and rural Mityana districts of Uganda. Each participant had whole blood samples collected at enrolment to assess baseline VL. Plasma HIV-1 RNA was quantified using COBAS Ampliprep /COBAS Taqman. Baseline VL below 400 RNA copies/ml was considered as viral suppression while baseline VL below 20 RNA copies/ml was considered uVL. Results The mean duration from the date of ART initiation to time of sample collection for baseline VL assessment was 4.4 days (SD 3.6). Of the 532 HIV-positive pregnant women enrolled in the FLC for Option B+ study and newly starting Option B+ without a self-reported history of prior ART use, 29 (5.5%) had uVL and 113 (21.4%) had suppressed VL at baseline. There was no association between participants’ age, gravidity, marital status, mean monthly income, educational level, disclosure of HIV status to partner, and uVL or viral suppression at baseline. However, non-disclosure of HIV status to any other person was associated with decreased odds of viral suppression at baseline (OR 0.640; 0.416–0.982). Conclusion Twenty-one percent of HIV-positive Ugandan pregnant women initiating ART (Option B+) showed virological suppression at baseline and were presumed to be “elite controllers” or to have misreported being ART-naive. Further studies are needed to better understand the biologic mechanisms of elite controllers among pregnant women as well as to differentiate elite controllers from concealed ART use. Trial Registration The trial was registered as NCT02515370 (04/08/2015) on Clinicaltrials.gov.

Background HIV infection is associated with significant neurocognitive deficits making maximization of cognitive function among children receiving antiretroviral therapy (ART) a public health imperative. Non-protease inhibitors (non-PIs) achieve higher drug levels in the cerebral spinal fluid (CSF) compared to PIs, potentially leading to better neurocognitive function by reducing CSF viral load and inflammation. ART that maximises children’s neurodevelopment and school achievement could result in improved quality of life and productivity as adults, but little research to date has examined whether non-PI ART is associated with better neurocognitive outcomes. We compared the neurocognitive function between children living with HIV receiving PI-based and non PI-based ART. Methods We recruited a consecutive sample of clinically stable Ugandan children living with HIV aged 5–12 years who received PI-based or non PI-based ART for ≥ 1 year (viral load Results We enrolled 76 children living with HIV; 34 on PI ART and 42 on non-PI ART. Mean (±SD) age was greater in the non-PI vs. PI group (9.5 ± 1.9 vs. 8.5 ± 2.0) years (p = 0.03). Children in the non-PI group had lower socioeconomic scores (5.7 ± 3.3 vs. 7.4 ± 2.8, p = 0.02). There was no difference in neurocognitive function between the groups (adjusted p > 0.05) for KABC and TOVA. Children in the PI group had better total BOT scores than their counterparts (46.07 ± 1.40) vs. 40.51 (1.24), p = 0.03). Conclusions We detected no difference in neurocognitive function among children on PI and non PI-based ART therapy based on KABC and TOVA tests. Children on PI based ART had better motor function than their counterparts. We recommend a prospective study with a larger sample size.

Background Whereas many adolescents and young people with HIV require the transfer of care from paediatric/adolescent clinics to adult ART clinics, this transition is beset with a multitude of factors that have the potential to hinder or facilitate the process, thereby raising ethical challenges of the transition process. Decisions made regarding therapy, such as when and how to transition to adult HIV care, should consider ethical benefits and risks. Understanding and addressing ethical challenges in the healthcare transition could ensure a smooth and successful transition. The purpose of this study was to analyze the ethical challenges of transitioning HIV care for adolescents into adult HIV clinics. Methods Data presented were derived from 191 adolescents attending nine different health facilities in Uganda, who constituted 18 focus group discussions. In the discussions, facilitators and barriers regarding adolescents transitioning to adult HIV clinics were explored. Guided by the Silences Framework for data interpretation, thematic data analysis was used to analyze the data. The principles of bioethics and the four-boxes ethics framework for clinical care (patient autonomy, medical indications, the context of care, and quality of life) were used to analyze the ethical issues surrounding the transition from adolescent to adult HIV care. Results The key emerging ethical issues were: reduced patient autonomy; increased risk of harm from stigma and loss of privacy and confidentiality; unfriendly adult clinics induce disengagement and disruption of the care continuum; patient preference to transition as a cohort, and contextual factors are critical to a successful transition. Conclusion The priority outcomes of the healthcare transition for adolescents should address ethical challenges of the healthcare transition such as loss of autonomy, stigma, loss of privacy, and discontinuity of care to ensure retention in HIV care, facilitate long-term self-care, offer ongoing all-inclusive healthcare, promote adolescent health and wellbeing and foster trust in the healthcare system. Identifying and addressing the ethical issues related to what hinders or facilitates successful transitions with targeted interventions for the transition process may ensure adolescents and young people with HIV infection remain healthy across the healthcare transition.

The goal of this paper is to review the prevention of mother-to-child HIV transmission (PMTCT) research that informed World Health Organization (WHO) guidelines for PMTCT and describe the impact of worldwide scale-up of PMTCT programs and antiretroviral therapy (ART) coverage. The impact of these interventions on new pediatric infections and infected children’s morbidity and mortality in sub-Saharan Africa are reviewed. The IMPAACT PROMISE study demonstrated that triple therapy consisting of tenofovir (TDF), lamivudine (3TC), and lopinavir/ritonavir (LPVr) or zidovudine (AZT), 3TC, and LPVr initiated in the first trimester reduced vertical transmission at 2 weeks of age to 0.6% and 0.5%, respectively, supporting the current WHO Option B+ recommendation for PMTCT. However, increased adverse pregnancy outcomes in the AZT- and TDF-based triple therapy arms were reported when compared with the AZT prophylaxis arm (low birth weight [20.4% and 16.9% vs. 8.9%; p = 0.004] and premature deliveries [19.7% and 18.5% vs. 13.5%; p = 0.09], respectively). Implementation of Option B+ for PMTCT has led to significant reductions in vertical transmission rates, including elimination of new pediatric infections in some countries. The WHO declared elimination of mother-to-child HIV transmission (MTCT) in Cuba in 2015 and in Armenia, Belarus, and Thailand in 2016. Globally, new pediatric HIV infections have declined significantly since the introduction of effective antiretroviral regimens for PMTCT. Perinatal HIV prevention clinical trials conducted in sub-Saharan Africa informed WHO PMTCT guidelines which led to implementation of PMTCT programs worldwide, leading to a 47% reduction in new pediatric infections since 2009. Support from The United States President's Emergency Plan for AIDS Relief (PEPFAR), the Global Fund for AIDS, Tuberculosis and Malaria, and UN agencies has enabled scale-up of national PMTCT programs, and increased antiretroviral coverage (47% globally) for infected children has led to a decline in HIV/AIDS-related mortality in children. Implementation strategies that improve retention in care and adherence to ART in pregnant and breastfeeding HIV-infected women is critical to ensure that more countries achieve the elimination of MTCT (eMTCT) targets. Assessing the effectiveness of new antiretroviral drugs, including fixed-dose combinations and long-acting formulations, is key to improving ART adherence and reducing the emergence of viral resistance mutations. In addition, interventions to prevent HIV transmission in adolescents and young adults is critical for reducing new HIV infections worldwide. Innovative interventions to improve adherence to ART are required to further improve the survival of HIV-infected children and adolescents.

To examine quality of life (QOL) in perinatally HIV-infected (PHIV) or HIV-exposed uninfected (PHEU) vs. healthy HIV-unexposed uninfected (HUU) children during school-age/adolescence.PHIV infection was diagnosed via DNA PCR. Current HIV status was confirmed by HIV rapid diagnostic test. Three HIV groups were defined: PHIV, PHEU, and HUU. QOL was assessed with proxy and self-report versions of the PedsQL™ 4.0 instrument at 6-18 years of age. QOL scores ranged from zero (least QOL) to 100 (highest QOL) in the following dimensions: combined QOL inventory (CQOLI), multi-dimensional vigor (MDV), general wellbeing (GWB), present functioning, and general cognitive functioning (CF). Multivariable linear regression models estimated HIV-related percent differences (β) in QOL scores and 95% confidence intervals (CI).Compared to HUU CQOLI deficits ranged from 6.5 to 9.2% (95% CI -15.4, -1.6), GWB deficit ranged from 6.5 to 10.5% (95% CI -16.0, -1.3), MDV deficit ranged from 6.8 to 11.6% (95% CI -14.5, 0.9), and CF deficit ranged from 9.7 to 13.1% for PHIV children. QOL deficits of similar magnitude and direction in most domains were observed for PHIV compared to PHEU. However, self-reported indicators of GWB (β = -3.5; 95% CI -9.0, 2.0) and present functioning (β = 4.0; 95% CI -4.6, 12.5) were similar for PHIV compared to PHEU. QOL scores were generally similar for PHEU compared to HUU.PHEU and HUU had similar QOL profile but PHIV predicted sustained deficits in multiple QOL domains. PHIV and PHEU children were similar with respect to general wellbeing and present functioning. Psychosocial and scholastic interventions in combination with HIV care are likely to improve QOL in PHIV.

Background The diagnosis of childhood tuberculosis remains a challenge worldwide. The Xpert MTB/RIF test, a rapid mycobacteria tuberculosis diagnostic tool, was recommended for use in children based on data from adult studies. We evaluated the performance of the Xpert MTB/RIF test for the diagnosis of childhood pulmonary tuberculosis using one induced sputum sample and described clinical characteristics associated with a positive Xpert MTB/RIF test. The sputum culture on both Lowenstein-Jensen (LJ) and Mycobacteria Growth Indicator Tube (MGIT) was the gold standard. Methods We consecutively enrolled 250 Ugandan children aged 2 months to 12 years with suspected pulmonary tuberculosis between January 2011 and January 2012 into a cross-sectional diagnostic study at a tertiary care facility in Uganda. Results We excluded data from 15 children (13 contaminated culture and 2 indeterminate MTB/RIF test results) and analysed 235 records. The Xpert MTB/RIF test had a sensitivity of 79.4% (95% CI 63.2 - 89.7) and a specificity of 96.5% (95% CI 93 – 98.3). The Xpert MTB/RIF test identified 13 of the 14 (92.9%) smear positive-culture positive and 14 of the 20 (70%) smear negative -culture positive cases. The Xpert MTB/RIF identified twice as many cases as the smear microscopy (79.4% Vs 41.2%). Age > 5 years (OR 3.3, 95% CI 1.4 – 7.4, p value 0.005), a history of Tuberculosis (TB) contact (OR 2.4, 95% CI 1.1 – 5.2, p value 0.03), and a positive tuberculin skin test (OR 4.1, 95% CI 1.7 – 10, p value 0.02) was associated with a positive Xpert MTB/RIF test. The median time to TB detection was 49.5 days (IQR 38.4-61.2) for LJ, and 6 days (IQR 5 – 11.5) for MGIT culture and 2 hours for the Xpert MTB/RIF test. Conclusion The Xpert MTB/RIF test on one sputum sample rapidly and correctly identified the majority of children with culture confirmed pulmonary tuberculosis with high specificity.

In resource-rich countries, bolus fluid expansion is routinely used for the treatment of poor perfusion and shock, but is less commonly used in many African settings. Controversial results from the recently completed FEAST (Fluid Expansion As Supportive Therapy) trial in African children have raised questions about the use of intravenous bolus fluid for the treatment of shock. Prior to the start of the trial, the Independent data monitoring committee (IDMC) developed stopping rules for the proof of benefit that bolus fluid resuscitation would bring. Although careful safety monitoring was put in place, there was less expectation that bolus fluid expansion would be harmful and differential stopping rules for harm were not formulated. In July 2010, two protocol amendments were agreed to increase the sample size from 2,880 to 3,600 children, and to increase bolus fluid administration. There was a non-significant trend against bolus treatment, but although the implications were discussed, the IDMC did not comment on the results, or on the amendments, in order to avoid inadvertent partial unblinding of the study. In January 2011, the trial was stopped for futility, as the combined intervention arms had significantly higher mortality (relative risk 1.46, 95% CI 1.13 to 1.90, P = 0.004) than the control arm. The stopping rule for proof of benefit was not achieved, and the IDMC stopped the trial with a lower level of significance (P = 0.01) due to futility and an increased risk of mortality from bolus fluid expansion in children enrolled in the trial. The basis for this decision was that the local standard of care was not to use bolus fluid for the care of children with shock in these African countries, and this was a different standard of care to that used in the UK. These decisions emphasize two important principles: firstly, the IDMC should avoid inadvertent unblinding of the trial by commenting on amendments, and secondly, when considering stopping a trial, the IDMC should be guided by the local standard of care rather than standards of care in other parts of the world.

Background. In previous studies, Delayed Type Hypersensitivity (DTH) skin testing has been shown to be affected by several factors including nutritional status, intercurrent infection, host immune status and previous exposure to the antigen being used.