SummaryBackgroundCross-resistance after first-line antiretroviral therapy (ART) failure is expected to impair activity of nucleoside reverse-transcriptase inhibitors (NRTIs) in second-line therapy for patients with HIV, but evidence for the effect of cross-resistance on virological outcomes is limited. We aimed to assess the association between the activity, predicted by resistance testing, of the NRTIs used in second-line therapy and treatment outcomes for patients infected with HIV.MethodsWe did an observational analysis of additional data from a published open-label, randomised trial of second-line ART (EARNEST) in sub-Saharan Africa. 1277 adults or adolescents infected with HIV in whom first-line ART had failed (assessed by WHO criteria with virological confirmation) were randomly assigned to a boosted protease inhibitor (standardised to ritonavir-boosted lopinavir) with two to three NRTIs (clinician-selected, without resistance testing); or with raltegravir; or alone as protease inhibitor monotherapy (discontinued after week 96). We tested genotypic resistance on stored baseline samples in patients in the protease inhibitor and NRTI group and calculated the predicted activity of prescribed second-line NRTIs. We measured viral load in stored samples for all patients obtained every 12–16 weeks. This trial is registered with Controlled-Trials.com (number ISRCTN 37737787) and ClinicalTrials.gov (number NCT00988039).FindingsBaseline genotypes were available in 391 (92%) of 426 patients in the protease inhibitor and NRTI group. 176 (89%) of 198 patients prescribed a protease inhibitor with no predicted-active NRTIs had viral suppression (viral load <400 copies per mL) at week 144, compared with 312 (81%) of 383 patients in the protease inhibitor and raltegravir group at week 144 (p=0·02) and 233 (61%) of 280 patients in the protease inhibitor monotherapy group at week 96 (p<0·0001). Compared with results with no active NRTIs, 95 (85%) of 112 patients with one predicted-active NRTI had viral suppression (p=0·3) and 20 (77%) of 26 patients with two or three active NRTIs had viral suppression (p=0·08). Over all follow-up, greater predicted NRTI activity was associated with worse viral load suppression (global p=0·0004).InterpretationGenotypic resistance testing might not accurately predict NRTI activity in protease inhibitor-based second-line ART. Our results do not support the introduction of routine resistance testing in ART programmes in low-income settings for the purpose of selecting second-line NRTIs.FundingEuropean and Developing Countries Clinical Trials Partnership, UK Medical Research Council, Institito de Salud Carlos III, Irish Aid, Swedish International Development Cooperation Agency, Instituto Superiore di Sanita, WHO, Merck.

SummaryBackgroundMillions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor plus raltegravir as an alternative second-line combination. We assessed whether this treatment option offers any advantage over the standard protease inhibitor plus two nucleoside reverse-transcriptase inhibitors (NRTIs) second-line combination after 144 weeks of follow-up in typical programme settings.MethodsWe analysed the 144-week outcomes at the completion of the EARNEST trial, a randomised controlled trial done in HIV-infected adults or adolescents in 14 sites in five sub-Saharan African countries (Uganda, Zimbabwe, Malawi, Kenya, Zambia). Participants were those who were no longer responding to non-NRTI-based first-line ART, as assessed with WHO criteria, confirmed by viral-load testing. Participants were randomly assigned to receive a ritonavir-boosted protease inhibitor (lopinavir 400 mg with ritonavir 100 mg, twice per day) plus two or three clinician-selected NRTIs (protease inhibitor plus NRTI group), protease inhibitor plus raltegravir (400 mg twice per day; protease inhibitor plus raltegravir group), or protease inhibitor monotherapy (plus raltegravir induction for first 12 weeks, re-intensified to combination therapy after week 96; protease inhibitor monotherapy group). Randomisation was by computer-generated randomisation sequence, with variable block size. The primary outcome was viral load of less than 400 copies per mL at week 144, for which we assessed non-inferiority with a one-sided α of 0·025, and superiority with a two-sided α of 0·025. The EARNEST trial is registered with ISRCTN, number 37737787.FindingsBetween April 12, 2010, and April 29, 2011, 1837 patients were screened for eligibility, of whom 1277 patients were randomly assigned to an intervention group. In the primary (complete-case) analysis at 144 weeks, 317 (86%) of 367 in the protease inhibitor plus NRTI group had viral loads of less than 400 copies per mL compared with 312 (81%) of 383 in the protease inhibitor plus raltegravir group (p=0·07; lower 95% confidence limit for difference 10·2% vs specified non-inferiority margin 10%). In the protease inhibitor monotherapy group, 292 (78%) of 375 had viral loads of less than 400 copies per mL; p=0·003 versus the protease inhibitor plus NRTI group at 144 weeks. There was no difference between groups in serious adverse events, grade 3 or 4 adverse events (total or ART-related), or events that resulted in treatment modification.InterpretationProtease inhibitor plus raltegravir offered no advantage over protease inhibitor plus NRTI in virological efficacy or safety. In the primary analysis, protease inhibitor plus raltegravir did not meet non-inferiority criteria. A regimen of protease inhibitor with NRTIs remains the best standardised second-line regimen for use in programmes in resource-limited settings.FundingEuropean and Developing Countries Clinical Trials Partnership (...

The origin of the coronavirus disease 2019 (COVID-19) in Wuhan China has been reported to be one of the lethal pandemics the world has ever faced. Though the first case was reported in December 2019, COVID-19 spread so rapidly to the majority of countries by March 2020 and was declared a global pandemic by the World Health Organization. COVID-19 pandemic led to increased morbidity and mortality within a very short period of time. COVID-19 pandemic caused schools, colleges, and universities to come to a closure in order to avoid further transmission and spread of the disease. The physical closure of schools, colleges, and universities has impacted students in several ways in that some students have reported suffering from anxiety, depression, and mood swings. COVID-19 has disrupted social interaction among students and has affected their family life. These impacts on students will eventually affect their academic performance and progression. Thus, learning institutions should put in measures to help students recover from the impacts of COVID-19.

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Background: The novel coronavirus disease (COVID-19) is a serious global health problem that has negatively impacted the mental health of students.Methods: We conducted an online descriptive cross-sectional study among 273 undergraduate pharmacy students at the University of Zambia from August to September 2020. A partial proportional odds regression model was used to determine the predictors of anxiety. All statistical tests were set at 95% confidence level (p<0.05).Results: A response rate of 70% was obtained with the majority of the students being female 51.6%. Of the 273 respondents, 23.8% did not experience anxiety, 34.4% experienced mild anxiety, 24.9% experienced moderate anxiety while 16.9% experienced severe anxiety about COVID-19. It was also found that 61.2% of students reported that their attention to mental health increased during the COVID-19 pandemic whereas 44.3% reported an increased resting time with a significant reduction in relaxation 51.3% and physical activity 45.4% time. Factors that affected mental health included; reduced family care (OR: 2.27; 95% CI: 1.09-4.74), not changing attention to mental health (OR: 0.33; 95% CI: 0.18-0.62), being in the final year of study (OR: 0.33; 95% CI: 0.13-0.84), reduced time of resting (OR: 2.10; 95% CI: 1.26-3.50) and feeling helpless (OR: 0.42; 95% CI:0.23-0.75).Conclusions: COVID-19 negatively impacted the mental health and physical activity of pharmacy students at the University of Zambia. This can have negative health and academic outcomes for students going forward. Higher learning institutions and key stakeholders should implement measures to aid students to recover from the impact of COVID-19 on their mental health and physical activity.

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection that emerged from China in December 2019 and is caused by severe acute respiratory syndrome coronavirus 2. Due to the airborne nature of its transmission, COVID-19 spread to the rest of the world rapidly. Thus, the World Health Organization declared COVID-19 a pandemic. This paper evaluated the factors that lead to self-medication in people suffering from respiratory tract infections such as COVID-19, and the consequences of practicing self-medication using antimicrobial agents. Most of the signs and symptoms of COVID-19 are also seen in infections such as malaria, flu, and the common cold. For this reason, and also due to poor healthcare-seeking behaviour, most people tend to self-medicate using medicines that are known to be effective against malaria, common cold, and COVID-19. Among the commonly used medicines in the practice of self-medication include antibacterials, antimalarials, and antivirals. Some vitamins such as vitamin C boost the immune system enabling it to provide effective defence mechanisms against microbes. However, self-medication may pose consequences such as the emergence of antimicrobial-resistant microorganisms, hypersensitivity reactions as well as dose-dependent toxicities viz dermatoxicity, cardiotoxicity, and hepatoxicity. Infectious diseases caused by antimicrobial-resistant microbes are difficult and, in some instances, impossible to treat thereby leading to increased morbidity and mortality among infected people. Consequently, antimicrobial resistance poses another global public health problem and requires a multisectoral approach to curb. It is our recommendation that all governments ensure that there are adequate medicines and efficient human resources in healthcare facilities as well as sufficient public awareness to prevent people from seeking self-medication.

Background: Several vaccines have been developed and administered since coronavirus disease 2019 (COVID-19) was declared a pandemic in March 2020. In April 2021, the authorities in Zambia administered the first doses of the Oxford-AstraZeneca® COVID-19 vaccine. However, little is known about the awareness and acceptability of the vaccines among the Zambian population. This study was undertaken to address this starting with undergraduate pharmacy students in Zambia. Materials and methods: A descriptive cross-sectional survey was conducted among 326 undergraduate pharmacy students in Zambia using an online semi-structured questionnaire from 12th to 25th April 2021 and analysed using Stata version 16. Test of associations were undertaken using Pearson chi-square test or Fisher's exact test as appropriate. The multivariable logistic regression was used to investigate the determinants of awareness and acceptability. All statistical tests were performed at a 5% significance level and 95% confidence level. Results: Among 326 participants, 98.8% were aware of the COVID-19 vaccination programme but only 24.5% would accept the vaccine should it be made available to them. Awareness of the COVID-19 vaccine was influenced by religious beliefs (aOR=0.01, 95% CI: 0.01 to 0.20, p=0.004). Being male (aOR=1.78, 95% CI: 1.05 to 3.02, p=0.034) and single (aOR=2.61, 95% CI: 1.04 to 6.55, p=0.041) was associated with higher odds of accepting the vaccine. Being unemployed (aOR=0.31, 95% CI: 0.15 to 0.66, p=0.002) was associated with lower odds of vaccine acceptancy. Barriers to acceptance of the vaccine were possible side effects (78.5%) and scepticism about its effectiveness to prevent COVID-19 (10.2%). Conclusion: There was significant vaccine hesitancy towards COVID-19 vaccines among Zambian pharmacy students despite their awareness about the vaccines. Health authorities must work collaboratively with the Universities and other institutions to mitigate vaccine hesitancy, especially with pharmacy students a key part of the future healthcare workforce overseeing disease prevention strategies. These findings can help guide future interventions to address vaccine hesitancy to reduce future transmission rates of this virus.

The coronavirus disease 2019 (COVID-19) pandemic is a global public health problem that has affected the globe in different ways. There is little information published on the challenges and lessons learnt in responding to the COVID-19 epidemic in Zambia. Objective: To establish Zambia's response, lessons and the challenges experienced in the fight against COVID-19. Results: Since the emergence of COVID-19, Zambia has experienced three waves, with the third wave being the most severe. The Zambian government responded positively and effectively to all three pandemics with the help of cooperating partners. Zambia adopted the World Health Organization (WHO) recommended prevention methods such as hand hygiene, masking up in public, physical distancing, avoiding crowded areas and staying at home to prevent the further spread of the disease. Additionally, surveillance of COVID-19 was strengthened, which led to the early detection of cases. Besides, there has been a strong call for all Zambian adults to receive the COVID-19 vaccine as a way of controlling the epidemic. However, since the launch of the COVID-19 vaccination programs, there has been a high level of vaccine hesitancy, causing Zambia to fall below the 10% of the adult population required to be vaccinated. Conclusion: The Zambian government put in place effective strategies in the fight against COVID-19. However, a lack of resources, misinformation, myths and vaccine hesitancy posed challenges in the fight against COVID-19 in Zambia. There is a need for continuous public education and sensitization on COVID-19