"Implementation of intensified COVID-19 vaccination optimization (ICVOPT) campaigns strategy in complex humanitarian emergency settings and hard-to-reach areas; a case of South Sudan".

INTRODUCTION: The COVID-19 pandemic is still a public health concern in South Sudan having caused suffering since the first case of COVID-19 was introduced on 28th February 2020. COVAX vaccines have since been introduced using a number of strategies including fixed site, temporary mobile, hit and run in flooded and conflict affected areas. We aim to describe the 2 ICVOPT campaigns that were conducted to improve the uptake and document lessons learnt during the initial rollout of the COVID-19 vaccination programin South Sudan between February 2022 and June 2022 each lasting for 7-days. METHODOLOGY: We conducted an operational cross-sectional descriptive epidemiological study of a series of the intensified COVID-19 vaccination Optimization (ICVOPT) campaigns from February 2022 to June 2022. Before the campaign, a bottom up micro-planning was conducted, validated by the County Health Departments (CHDs) and national MOH team. Each of the 2 campaigns lasted for 7 days targeting 30% of the eligible unvaccinated target population who were18 years and above. Each team consisted of 2 vaccinators, 2 recorders and 1 mobilizer. The teams employed both fixed site, temporary mobile, hit and run in flooded and conflict affected areas. The number of teams were calculated based on the daily workload per day (80 persons per team/day) for the duration of the campaigns. RESULTS: A total of 444,030 individuals were vaccinated with primary series COVID-19 vaccine (J&J) out of the targeted 635,030 persons. This represented 69.9% of target population in the selected 28 counties and 10 states of South Sudan in 7 days' ICVOPT campaigns. More eligible persons were reached in 7 days campaigns than the 9 months of rollout of the COVID-19 vaccine prior to ICVOPT campaigns using the fixed site strategy at the health facility posts. CONCLUSION: Intensified COVID-19 vaccination Optimization (ICVOPT) campaigns were vital and fast in scaling up vaccination coverages as compared to the fixed site vaccination strategies (2022 progress report on the Global Action Plan for Healthy Lives and Well-being for All Stronger collaboration for an equitable and resilient recovery towards the health-related Sustainable Development Goals, incentivizing collaboration, 2022) in complex humanitarian emergency settings and hard-to-reach areas of South Sudan.

Assessment of second-line antiretroviral regimens for HIV therapy in Africa.

BACKGROUND: The efficacy and toxic effects of nucleoside reverse-transcriptase inhibitors (NRTIs) are uncertain when these agents are used with a protease inhibitor in second-line therapy for human immunodeficiency virus (HIV) infection in resource-limited settings. Removing the NRTIs or replacing them with raltegravir may provide a benefit. METHODS: In this open-label trial in sub-Saharan Africa, we randomly assigned 1277 adults and adolescents with HIV infection and first-line treatment failure to receive a ritonavir-boosted protease inhibitor (lopinavir-ritonavir) plus clinician-selected NRTIs (NRTI group, 426 patients), a protease inhibitor plus raltegravir in a superiority comparison (raltegravir group, 433 patients), or protease-inhibitor monotherapy after 12 weeks of induction therapy with raltegravir in a noninferiority comparison (monotherapy group, 418 patients). The primary composite end point, good HIV disease control, was defined as survival with no new World Health Organization stage 4 events, a CD4+ count of more than 250 cells per cubic millimeter, and a viral load of less than 10,000 copies per milliliter or 10,000 copies or more with no protease resistance mutations at week 96 and was analyzed with the use of imputation of data (≤4%). RESULTS: Good HIV disease control was achieved in 60% of the patients (mean, 255 patients) in the NRTI group, 64% of the patients (mean, 277) in the raltegravir group (P=0.21 for the comparison with the NRTI group; superiority of raltegravir not shown), and 55% of the patients (mean, 232) in the monotherapy group (noninferiority of monotherapy not shown, based on a 10-percentage-point margin). There was no significant difference in rates of grade 3 or 4 adverse events among the three groups (P=0.82). The viral load was less than 400 copies per milliliter in 86% of patients in the NRTI group, 86% in the raltegravir group (P=0.97), and 61% in the monotherapy group (P<0.001). CONCLUSIONS: When given with a protease inhibitor in second-line therapy, NRTIs retained substantial virologic activity without evidence of increased toxicity, and there was no advantage to replacing them with raltegravir. Virologic control was inferior with protease-inhibitor monotherapy. (Funded by European and Developing Countries Clinical Trials Partnership and others; EARNEST Current Controlled Trials number, ISRCTN37737787, and ClinicalTrials.gov number, NCT00988039.).

Peripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial.

Sensory peripheral neuropathy (PN) remains a common complication in HIV-positive patients despite effective combination anti-retroviral therapy (ART). Data on PN on second-line ART is scarce. We assessed PN using a standard tool in patients failing first-line ART and for 96 weeks following a switch to PI-based second-line ART in a large Randomised Clinical Trial in Sub-Saharan Africa. Factors associated with PN were investigated using logistic regression. Symptomatic PN (SPN) prevalence was 22% at entry (N = 1,251) and was associated (p < 0.05) with older age (OR = 1.04 per year), female gender (OR = 1.64), Tuberculosis (TB; OR = 1.86), smoking (OR = 1.60), higher plasma creatinine (OR = 1.09 per 0.1 mg/dl increase), CD4 count (OR = 0.83 per doubling) and not consuming alcohol (OR = 0.55). SPN prevalence decreased to 17% by week 96 (p = 0.0002) following similar trends in all study groups (p = 0.30). Asymptomatic PN (APN) increased over the same period from 21 to 29% (p = 0.0002). Signs suggestive of PN (regardless of symptoms) returned to baseline levels by week 96. At weeks 48 and 96, after adjusting for time-updated associations above and baseline CD4 count and viral load, SPN was strongly associated with TB (p < 0.0001). In summary, SPN prevalence was significantly reduced with PI-based second-line therapy across all treatment groups, but we did not find any advantage to the NRTI-free regimens. The increase of APN and stability of PN-signs regardless of symptoms suggest an underlying trend of neuropathy progression that may be masked by reduction of symptoms accompanying general health improvement induced by second-line ART. SPN was strongly associated with isoniazid given for TB treatment.