EDCTP Alumni Network

Introduction: The novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), etiological agent of coronavirus disease 2019 (COVID-19) was first reported in China in December 2019 and spread worldwide. As of March 6th, 2021, there have been 116,670,105 million confirmed cases globally including 2,592,085 deaths. COVID-19 cases have been reported in 219 countries and territories, creating global panic. Mozambique has witnessed the evolution of COVID-19 epidemic associated with the weakness of health system, mostly in terms of laboratory diagnosis capacity, concerns on compliance to effective public health measures including physical distancing, use of masks in crowded indoor areas, hand hygiene, isolation and quarantine of people. Methodology: The data included in this study were collected from published articles regarding COVID-19 imported cases and severity in Africa, especially in Mozambique. Additionally, official documents of COVID-19 epidemiology from Minister of Health and National Institute of Health of Mozambique from 22nd of March 2020 to 1st of August 2020 were included. Results: The SARS-CoV-2 strains imported mainly from South Africa and European countries might have been playing an important role on COVID-19 epidemic evolution in Mozambique. Conclusions: These circulating strains in the country, might be similar enough to the strains found in other countries, yet the genomic characterization is needed particularly during the phase of borders reopening through understanding the source of infections and guiding the implementation of containment and mitigation measures in the country.

Background: While super-boosted lopinavir/ritonavir (LPV/r; ratio 4:4 instead of 4:1) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice many different LPV/r dosing strategies are applied due to poor availability of paediatric separate ritonavir formulations needed to super-boost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPV/r dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB)-treatment.

Methods: This was a 2-arm pharmacokinetic sub-study nested within the EMPIRICAL trial (#NCT03915366). Infants aged 1-12 months recruited into the main study were administered LPV/r according to local guidelines and drug availability either with or without rifampicin-based TB-treatment; during rifampicin co-treatment they received double-dosed (ratio 8:2) or semi-superboosted LPV/r (adding a ritonavir 100mg crushed tablet to the evening LPV/r dose). Six blood samples were taken over 12 hours after intake of LPV/r.

Results: In total, 14/16 included infants had evaluable pharmacokinetic curves; 9/14 had rifampicin co-treatment (5 received double-dosed and 4 semi-superboosted LPV/r). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0kg (5.2-6.8) and 10/14 were male. Of those receiving rifampicin, 6/9 (67%) infants had LPV C trough <1.0mg/L compared to 1/5 (20%) in the control arm. LPV apparent oral clearance was 3.3-fold higher for infants receiving rifampicin.

Conclusion: Double-dosed or semi-superboosted LPV/r for infants aged 1-12 months receiving rifampicin resulted in substantial proportions of subtherapeutic LPV levels. There is an urgent need for data on alternative antiretroviral regimens in infants with HIV/TB co-infection, including twice-daily dolutegravir.

While there is ample evidence that antiretroviral therapy (ART) can improve cognitive outcomes in older children living with HIV, encephalopathy in infants has historically been considered an advanced disease presentation with less likelihood of neurodevelopmental recovery on treatment. More recent studies suggest that timely ART can halt encephalopathic disease progression and even lead to symptom resolution. Here we present a case of an HIV-positive infant diagnosed with encephalopathy who experienced impressive and rapid improvement with a multi-disciplinary care approach that included physical and occupational therapy and ART.