Factors associated with viral load non-suppression in people living with HIV on ART in Nigeria: cross-sectional analysis from 2017 to 2021.

OBJECTIVES: Identify factors (demographic and clinical) associated with a non-suppressed viral load (VL) of people living with HIV (PLHIV) on antiretroviral therapy (ART) in Nigeria. DESIGN: Cross-sectional study. SETTING: Sixteen US Agency for International Development supported states in Nigeria. PARTICIPANTS: 585 632 PLHIV on ART. PRIMARY OUTCOME MEASURES: VL non-suppression (defined as having a VL of at least 1000 HIV RNA copies per mL of plasma). χ2 testing and multivariable modified Poisson regression with robust variance estimates were conducted on routinely collected ART programme data. RESULTS: Sixty-six per cent of the study population were females. The largest age groups were 25-34 and 35-44, accounting for 32.1% and 31.1%, respectively. Males had a 9% greater likelihood (adjusted prevalence ratio, APR=1.09) of being non-suppressed. The age groups below 60+ (APR=0.67) had a higher likelihood of a non-suppressed VL, with the highest in the 0-14 age group (APR=2.38). Clients enrolled at tertiary and secondary level facilities had the greatest likelihood of a non-suppressed VL. Clients who started ART between 2010 and 2015 had the greatest likelihood of viral non-suppression (APR=6.19). A shorter time on ART (<1 year (APR=3.92)) was associated with a higher likelihood of a non-suppressed VL. Clients receiving care at private facilities had a lower likelihood of viral non-suppression in the adjusted model. Clients in the Edo (APR=2.66) and Niger (APR=2.54) states had the greatest likelihood of viral non-suppression. CONCLUSIONS: Targeting males, clients of younger age, those on treatment for less than 3 years, clients at tertiary and secondary health facilities, small and medium facilities, and clients in the Edo, Niger and Borno states for interventions could lead to improvements in VL suppression in Nigeria. The independent factors associated with a non-suppressed VL can guide improvements in ART programme development and VL suppression of PLHIV on ART in Nigeria.

Treatment outcomes and costs of a simplified antiretroviral treatment strategy for hepatitis C among Hepatitis C Virus and Human Immuno deficiency Virus co-infected patients in Ukraine.

Background and Aim: To demonstrate the use of a standard dose of ledipasvir (LDV) and sofosbuvir (SOF), with or without ribavirin, to treat hepatitis C and hepatitis C/HIV co-infection in Ukraine. Methods: Eligible HCV viraemic adults from two clinics in Kyiv were treated with LDV/SOF with or without weight-based ribavirin for 12 weeks. Clinical assessments were performed at screening and at week 24, and as needed; treatment was dispensed every 4 weeks. The primary outcome was sustained virologic response (SVR) 12 weeks after treatment, with analysis by intention to treat. Cost per patient was estimated in USD (2018) over the 24-week period. Results: Of 868 patients included in the study and initiated on therapy, 482 (55.5%) were co-infected with HIV. The common genotypes were 1 (74.1%) and 3 (22%). Overall, SVR was achieved in 831 of the 868 patients (95.7%). SVR in patients with hepatitis C alone and hepatitis C/HIV co-infection was 98.4% and 93.6%, respectively. Adverse events were infrequent and usually mild. Using generic medication, cost per patient was estimated at US$680. Conclusion: A standard dose of LDV and SOF, with ribavirin as per protocol, resulted in good outcomes for patients with both hepatitis C alone and co-infected with hepatitis C/HIV. Program costs in Ukraine were modest using generic medication.

Voluntary medical male circumcision in selected provinces in South Africa: Outcomes from a programmatic setting.

INTRODUCTION: Voluntary medical male circumcision (VMMC) remains an effective biomedical intervention for HIV prevention in high HIV prevalence countries. In South Africa, United States Agency for International Development VMMC partners provide technical assistance to the Department of Health, at national and provincial levels in support of the establishment of VMMC sites as well as in providing direct VMMC services at site level since April 2012. We describe the outcomes of the Right to Care (RTC) VMMC program implemented in South Africa from 2012 to 2017. METHODS: This retrospective study was undertaken at RTC supported facilities across six provinces. Young males aged ≥10 years who presented at these facilities from 1 July 2012 to 31 September 2017 were included. Outcomes were VMMC uptake, HIV testing uptake and rate of adverse events (AEs). Using a de-identified observational database of these clients, summary statistics of the demographic characteristics and outcomes were calculated. RESULTS: There were a total 1,001,226 attendees of which 998,213 (99.7%) were offered VMMC and had a median age of 15 years (IQR = 12-23 years). Of those offered VMMC, 99.6% (994,293) consented, 96.7% (965,370) were circumcised and the majority (46.3%) were from Gauteng province. HIV testing uptake was 71% with a refusal rate of 15%. Of the newly diagnosed HIV positives, 64% (6,371 / 9,972) referrals were made. The rate of AEs, defined as bleeding, infection, and insufficient skin removal) declined from 3.26% in 2012 to 1.17% in 2017. There was a reduction in infection-related AEs from 2,448 of the 2,602 adverse events (94.08%) in 2012 to 129 of the 2,069 adverse events (6.23%) in 2017. CONCLUSION: There was a high VMMC uptake with a decline in AEs over time. Adolescent men contributed the most to the circumcised population, an indication that the young population accesses medical circumcision more. VMMC programs need to implement innovative demand creation strategies to encourage older males (20-34 years) at higher risk of HIV acquisition to get circumcised for immediate impact in reduction of HIV incidence. HIV prevalence in the total population increased with increasing age, notably in clients above 25 years.

Persistent Symptoms among Frontline Health Workers Post-Acute COVID-19 Infection.

Growing evidence shows that a significant number of patients with COVID-19 experience persistent symptoms, also known as long COVID-19. We sought to identify persistent symptoms of COVID-19 in frontline workers at Right to Care South Africa, who are past the acute phase of illness, using a cross-sectional survey. We analysed data from 207 eligible COVID-19 positive frontline workers who participated in a two-month post-COVID-19 online self-administered survey. The survey response rate was 30%; of the 62 respondents with a median age of 33.5 years (IQR= 30-44 years), 47 (76%) were females. The majority (n = 55; 88.7%) self-isolated and 7 (11.3%) were admitted to hospital at the time of diagnosis. The most common comorbid condition reported was hypertension, particularly among workers aged 45-55 years. The most reported persistent symptoms were characterised by fatigue, anxiety, difficulty sleeping, chest pain, muscle pain, and brain fog. Long COVID-19 is a serious phenomenon, of which much is still unknown, including its causes, how common it is especially in non-hospitalised healthcare workers, and how to treat it. Given the rise in COVID-19 cases, the prevalence of long COVID-19 is likely to be substantial; thus, the need for rehabilitation programs targeted at each persistent COVID-19 symptom is critical.

Determining the lower limit of detection required for HCV viral load assay for test of cure following direct-acting antiviral-based treatment regimens: Evidence from a global data set.

Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post-treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5973 cases of detectable viraemia at SVR12 from the combined data set. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viraemia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR = 1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure.

Treatment outcomes and costs of a simplified antiviral treatment strategy for hepatitis C among monoinfected and HIV and/or hepatitis B virus-co-infected patients in Myanmar.

Access to hepatitis C virus (HCV) testing and treatment is limited in Myanmar. We assessed an integrated HIV and viral hepatitis testing and HCV treatment strategy. Sofosbuvir/velpatasvir (SOF/VEL) ± weight-based ribavirin for 12 weeks was provided at three treatment sites in Myanmar and sustained virologic response (SVR) assessed at 12 weeks after treatment. Participants co-infected with HBV were treated concurrently with tenofovir. Cost estimates in 2018 USD were made at Yangon and Mandalay using standard micro-costing methods. 803 participants initiated SOF/VEL; 4.8% were lost to follow-up. SVR was achieved in 680/803 (84.6%) by intention-to-treat analysis. SVR amongst people who inject drugs (PWID) was 79.7% (381/497), but 92.5% among PWID on opioid substitution therapy (OST) (74/80), and 97.4% among non-PWID (298/306). Utilizing data from 492 participants, of whom 93% achieved SVR, the estimated average cost of treatment per patient initiated was $1030 (of which 54% were medication costs), with a production cost per successful outcome (SVR) of $1109 and real-world estimate of $1250. High SVR rates were achieved for non-PWID and PWID on OST. However, the estimated average cost of the intervention (under the assumption of no genotype testing and reduced real-world effectiveness) of $1250/patient is unaffordable for a national elimination strategy. Reductions in the cost of antivirals and linkage to social and behavioural health services including substance use disorder treatment to increase retention and adherence to treatment are critical to HCV elimination in this population.

Genotype E: The neglected genotype of hepatitis B virus.

Hepatitis B virus (HBV) (sub)genotypes A1, D3 and E circulate in sub-Saharan Africa, the region with one of the highest incidences of HBV-associated hepatocellular carcinoma globally. Although genotype E was identified more than 20 years ago, and is the most widespread genotype in Africa, it has not been extensively studied. The current knowledge status and gaps in its origin and evolution, natural history of infection, disease progression, response to antiviral therapy and vaccination are discussed. Genotype E is an African genotype, with unique molecular characteristics that is found mainly in Western and Central Africa and rarely outside Africa except in individuals of African descent. The low prevalence of this genotype in the African descendant populations in the New World, phylogeographic analyses, the low genetic diversity and evidence of remnants of genotype E in ancient HBV samples suggests the relatively recent re-introduction into the population. There is scarcity of information on the clinical and virological characteristics of genotype E-infected patients, disease progression and outcomes and efficacy of anti-HBV drugs. Individuals infected with genotype E have been characterised with high hepatitis B e antigen-positivity and high viral load with a lower end of treatment response to interferon-alpha. A minority of genotype E-infected participants have been included in studies in which treatment response was monitored. Of concern is that current guidelines do not consider patients infected with genotype E. Thus, there is an urgent need for further large-scale investigations into genotype E, the neglected genotype of HBV.

In Vitro Systems for Studying Different Genotypes/Sub-Genotypes of Hepatitis B Virus: Strengths and Limitations.

Hepatitis B virus (HBV) infects the liver resulting in end stage liver disease, cirrhosis, and hepatocellular carcinoma. Despite an effective vaccine, HBV poses a serious health problem globally, accounting for 257 million chronic carriers. Unique features of HBV, including its narrow virus-host range and its hepatocyte tropism, have led to major challenges in the development of suitable in vivo and in vitro model systems to recapitulate the HBV replication cycle and to test various antiviral strategies. Moreover, HBV is classified into at least nine genotypes and 35 sub-genotypes with distinct geographical distributions and prevalence, which have different natural histories of infection, clinical manifestation, and response to current antiviral agents. Here, we review various in vitro systems used to study the molecular biology of the different (sub)genotypes of HBV and their response to antiviral agents, and we discuss their strengths and limitations. Despite the advances made, no system is ideal for pan-genotypic HBV research or drug development and therefore further improvement is required. It is necessary to establish a centralized repository of HBV-related generated materials, which are readily accessible to HBV researchers, with international collaboration toward advancement and development of in vitro model systems for testing new HBV antivirals to ensure their pan-genotypic and/or customized activity.

Hepatitis C virus genotype 5a subgenomic replicons for evaluation of direct-acting antiviral agents.

Hepatitis C virus (HCV) exists as six major genotypes that differ in geographical distribution, pathogenesis, and response to antiviral therapy. In vitro replication systems for all HCV genotypes except genotype 5 have been reported. In this study, we recovered genotype 5a full-length genomes from four infected voluntary blood donors in South Africa and established a G418-selectable subgenomic replicon system using one of these strains. The replicon derived from the wild-type sequence failed to replicate in Huh-7.5 cells. However, the inclusion of the S2205I amino acid substitution, a cell culture-adaptive change originally described for a genotype 1b replicon, resulted in a small number of G418-resistant cell colonies. HCV RNA replication in these cells was confirmed by quantification of viral RNA and detection of the nonstructural protein NS5A. Sequence analysis of the viral RNAs isolated from multiple independent cell clones revealed the presence of several nonsynonymous mutations, which were localized mainly in the NS3 protein. These mutations, when introduced back into the parental backbone, significantly increased colony formation. To facilitate convenient monitoring of HCV RNA replication levels, the mutant with the highest replication level was further modified to express a fusion protein of firefly luciferase and neomycin phosphotransferase. Using such replicons from genotypes 1a, 1b, 2a, 3a, 4a, and 5a, we compared the effects of various HCV inhibitors on their replication. In conclusion, we have established an in vitro replication system for HCV genotype 5a, which will be useful for the development of pan-genotype anti-HCV compounds.

Antibiotic Resistance Profiles of Escherichia coli Isolated from Different Water Sources in the Mmabatho Locality; Northwest Province; South Africa

The antibiotic resistance profiles of Escherichia coli (E. coli); isolated from different water sources in the Mmabatho locality were evaluated. Water samples were collected from the local wastewater- and water-treatment plants; the Modimola Dam and homes in the area; and then analysed for the presence of E. coli; using standard methods. Presumptive isolates obtained were confirmed by the analytical profile index test. Antibiotic susceptibility testing was performed by the disc diffusion method. Of the 230 E. coli isolates tested; marked antibiotic resistances (over 70) were observed for erythromycin; tetracycline; ampicillin; chloramphenicol and norfloxacin. Multiple antibiotic resistance patterns were also compiled. Overall; the phenotype T-Ap-E was frequent for E. coli isolated from the local wastewater and water-treatment plants; Modimola Dam and tap water. Cluster analysis performed showed a unique antibiotic resistance pattern which suggested a link between isolates from all sampling points. The findings indicated that improper wastewater treatment may have a potential impact on the dissemination and survival of E. coli; as well as other pathogenic bacteria in water for human and animal consumption. This may result in water- and food-borne disease outbreaks with a negative effect on antibiotic therapy