Low-level viraemia: An emerging concern among people living with HIV in Uganda and across sub-Saharan Africa.

Attaining viral load (VL) suppression for over 95% of the people living with HIV on antiretroviral therapy is a fundamental step in enabling Uganda and other sub-Saharan African countries to achieve global Sustainable Development Goal targets to end the HIV/AIDS epidemic by 2030. In line with the 2013 World Health Organization recommendations, several sub-Saharan African countries, including Uganda, use a threshold of 1000 HIV viral RNA copies/mL to determine HIV viral non-suppression. The United States Centers for Disease Control and Prevention and the International Association of Providers of AIDS Care deem this threshold very high, and hence recommend using 200 copies/mL to determine viral non-suppression. Using 1000 copies/mL as a threshold ignores people living with HIV who have low-level viraemia (LLV; HIV VL of at least 50 copies/mL but less than 1000 copies/mL). Despite the 2021 World Health Organization recommendations of using intensive adherence counselling for people living with HIV with LLV, several sub-Saharan African countries have no interventions to address LLV. However, recent studies have associated LLV with increased risks of HIV drug resistance, virologic failure and transmission. The purpose of this narrative review is to provide insights on the emerging concern of LLV among people living with HIV receiving antiretroviral therapy in sub-Saharan Africa. The review also provides guidance for Uganda and other sub-Saharan African countries to implement immediate appropriate interventions like intensive adherence counselling, reducing VL thresholds for non-suppression and conducting more research to manage LLV which threatens progress towards ending HIV by 2030.

Current malaria infection, previous malaria exposure, and clinical profiles and outcomes of COVID-19 in a setting of high malaria transmission: an exploratory cohort study in Uganda.

BACKGROUND: The potential effects of SARS-CoV-2 and Plasmodium falciparum co-infection on host susceptibility and pathogenesis remain unknown. We aimed to establish the prevalence of malaria and describe the clinical characteristics of SARS-CoV-2 and P falciparum co-infection in a high-burden malaria setting. METHODS: This was an exploratory prospective, cohort study of patients with COVID-19 who were admitted to hospital in Uganda. Patients of all ages with a PCR-confirmed diagnosis of SARS-CoV-2 infection who had provided informed consent or assent were consecutively enrolled from treatment centres in eight hospitals across the country and followed up until discharge or death. Clinical assessments and blood sampling were done at admission for all patients. Malaria diagnosis in all patients was done by rapid diagnostic tests, microscopy, and molecular methods. Previous P falciparum exposure was determined with serological responses to a panel of P falciparum antigens assessed using a multiplex bead assay. Additional evaluations included complete blood count, markers of inflammation, and serum biochemistries. The main outcome was overall prevalence of malaria infection and malaria prevalence by age (including age categories of 0-20 years, 21-40 years, 41-60 years, and >60 years). The frequency of symptoms was compared between patients with COVID-19 with P falciparum infection versus those without P falciparum infection. The frequency of comorbidities and COVID-19 clinical severity and outcomes was compared between patients with low previous exposure to P falciparum versus those with high previous exposure to P falciparum. The effect of previous exposure to P falciparum on COVID-19 clinical severity and outcomes was also assessed among patients with and those without comorbidities. FINDINGS: Of 600 people with PCR-confirmed SARS-CoV-2 infection enrolled from April 15, to Oct 30, 2020, 597 (>99%) had complete information and were included in our analyses. The majority (502 [84%] of 597) were male individuals with a median age of 36 years (IQR 28-47). Overall prevalence of P falciparum infection was 12% (95% CI 9·4-14·6; 70 of 597 participants), with highest prevalence in the age groups of 0-20 years (22%, 8·7-44·8; five of 23 patients) and older than 60 years (20%, 10·2-34·1; nine of 46 patients). Confusion (four [6%] of 70 patients vs eight [2%] of 527 patients; p=0·040) and vomiting (four [6%] of 70 patients vs five [1%] of 527 patients; p=0·014] were more frequent among patients with P falciparum infection than those without. Patients with low versus those with high previous P falciparum exposure had a increased frequency of severe or critical COVID-19 clinical presentation (16 [30%] of 53 patients vs three [5%] of 56 patients; p=0·0010) and a higher burden of comorbidities, including diabetes (12 [23%] of 53 patients vs two [4%] of 56 patients; p=0·0010) and heart disease (seven [13%] of 53 patients vs zero [0%] of 56 patients; p=0·0030). Among patients with no comorbidities, those with low previous P falciparum exposure still had a higher proportion of cases of severe or critical COVID-19 than did those with high P falciparum exposure (six [18%] of 33 patients vs one [2%] of 49 patients; p=0·015). Multivariate analysis showed higher odds of unfavourable outcomes in patients who were older than 60 years (adjusted OR 8·7, 95% CI 1·0-75·5; p=0·049). INTERPRETATION: Although patients with COVID-19 with P falciparum co-infection had a higher frequency of confusion and vomiting, co-infection did not seem deleterious. The association between low previous malaria exposure and severe or critical COVID-19 and other adverse outcomes will require further study. These preliminary descriptive observations highlight the importance of understanding the potential clinical and therapeutic implications of overlapping co-infections. FUNDING: Malaria Consortium (USA).

Factors affecting virological non-suppression amongst HIV-positive patients on antiretroviral therapy: Uganda, August 2014 - July 2015

Introduction: virological suppression is a critical indicator for HIV treatment success and reduction in HIV transmission risk. However, despite the increasing number of people on antiretroviral therapy (ART), there is limited information about non-suppression and its determinants among HIV-positive (HIV+) individuals enrolled in care in many resource-limited settings. This study estimated the virological non-suppression rates amongst HIV+ patients who had been on ART for at least 6 months and the factors associated with non-suppression. Methods: a descriptive cross-sectional study was conducted using routinely collected data from viral load testing samples from 100,678 HIV+ patients enrolled in HIV care across the country between August 2014 and July 2015. Viral load testing was conducted at the Central Public Health Laboratories in Kampala, Uganda. We extracted data on socio-demographic, clinical and viral load testing results. We defined virological non-suppression as having ≥ 1000 copies of viral RNA/ml of blood for plasma or ≥ 5000 copies of viral RNA/ml of blood for dry blood spots. We used logistic regression to identify factors associated with virological non-suppression. Results: majority of the patients (68%) were females. The overall non-suppression rate was 11%. Second-time testers had a higher non-suppression rate than first-time testers (50% vs. 10%, OR = 7.0, 95%CI = 6.2-7.9); and children aged < 5 years (29%, OR = 5.3, 95%CI = 4.8-6.0) and adolescents aged 15-19 (27%, OR = 4.1, 95%CI = 3.7-4.5) had higher non-suppression rates than persons of other age groups. Non-suppression rates were also higher among suspected treatment failures (29%, OR = 4.0, 95%CI = 3.7-4.4), patients with reported adherence levels < 85% (35%, OR = 3.4, 95%CI = 3.0-3.9), and patients with active TB (20%, OR = 2.0, 95%CI = 1.5-2.3) than those without these conditions. Breastfeeding (6%, OR = 0.61, 95%CI = 0.54-0.69) and pregnant women (8%, OR = 0.77, 95%CI = 0.65-0.91) had lower non-suppression rates than non-breastfeeding and non-pregnant women (10%). Conclusion: virological non-suppression was associated with second time testers, young age, poor adherence, and TB co-infection. To maximize the benefits of the expanded ART, we recommend close follow-up and intensified targeted adherence support for second time testers, children and adolescents. Adherence to standard guidelines for managing TB/HIV co-infections should be emphasized by all ART clinics