New infections and HIV-1 subtypes among febrile persons and blood donors in Oyo State, Nigeria.

PURPOSE: There were approximately 37.9 million persons infected with HIV in 2018 globally, resulting in 770,000 deaths annually. Over 50% of this infection and deaths occur in sub-Saharan Africa, with countries like Nigeria being seriously affected. Nigeria has one of the highest rates of new infections globally. To control HIV infection in Nigeria, there is a need to continually screen high-risk groups for early HIV infection and subtypes using very sensitive methods. In this study, new HIV-1 infection and circulating HIV-1 subtypes among febrile persons and blood donors were determined. Performance characteristics of three commercial EIA kits were also evaluated. METHODS: In total, 1028 participants were recruited for the study. New HIV-1 infection and subtypes were determined using enzyme immunoassays and molecular techniques, respectively. Sensitivity, specificity, predictive values, and agreements were compared among the EIA kits using PCR-confirmed HIV-positive and negative samples. RESULTS: The overall prevalence of HIV infection in this study was 5.35%. The rate of new HIV infection was significantly different (p < .03674) among 1028 febrile persons (Ibadan: 2.22%; Saki: 1.36%) and blood donors (5.07%) studied. Three subtypes, CRF02_AG, A, and G, were found among those with new HIV infection. Whereas the commercial ELISA kits had very high specificities (94.12%, 100%, and 100%) for HIV-1 detection, Alere Determine HIV-1 antibody rapid kit had the lowest sensitivity score (50%). CONCLUSION: Genetic diversity of HIV-1 strains among infected individuals in Oyo State, Nigeria, is still relatively high. This high level of diversity of HIV-1 strains may impact the reliability of diagnosis of the virus in Nigeria and other African countries where many of the virus strains co-circulate.

Phylogeny of partial gag, pol and env genes show predominance of HIV-1G and CRF02_AG with emerging recombinants in south-eastern Nigeria.

Human Immunodeficiency Virus is characterized by high degree of genetic diversity with marked differences in its geographic distribution even within a country. This study was designed to identify the strains of HIV-1 circulating among infected individuals in southeastern parts of Nigeria. Genomic DNA was extracted from blood samples of 30 HIV-1 infected individuals from Anambra, Delta and Imo states of southeastern Nigeria. Portions of the genome corresponding to entire p24 gag, entire protease and C2-V3 env genes were amplified by nested PCR, sequenced using Sanger's method and phylogenetically analysed. Out of the 30 samples sequenced, 17, 28 and 14 readable sequences were obtained for gag, pol and env regions respectively. The most prevalent subtypes were CRF02_AG (41.2% in gag, 57.1% in pol protease and 50.0% in env) and G (29.4% in gag, 35.7% in pol protease and 35.7% in env). Other subtypes identified include A (17.7% in gag, 7.1% in env) and J (7.1% in env). Also 2 sequences each in gag (11.8%) and pol protease (7.1%) regions were unclassified but preliminary analysis showed they are recombinants. Furthermore, 71.4% of the isolates with sequences in the 3 regions and 26.7% of those with sequences in 2 genomic regions were recombinant forms. CRF02_AG and subtype G are the predominant HIV-1 strains circulating among infected individuals in southeastern Nigeria. Preliminary analysis results of unclassified sequences suggest that they are new recombinants.

Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria.

Acquisition of resistance mutations by HIV-1 isolates causes treatment failure among infected patients receiving antiretroviral therapy (ART). This study determined patterns of drug-resistance mutations (DRMs) among HIV-1 isolates from patients receiving first-line ART in South-eastern Nigeria. Blood samples were collected from HIV-1 infected patients accessing antiretroviral treatment centers at General Hospital Awo-Omamma, Imo state, State Hospital Asaba, Delta state and St Joseph's Catholic Hospital Adazi, Anambra state and used for HIV-1 DNA sequencing and phylogenetic analysis. DRMs were scored using combination of Stanford algorithm and the 2015 International Antiviral Society-USA list while drug susceptibility was predicted using Stanford algorithm. Twenty eight of the HIV-1 isolates were sequenced and identified as subtypes G (35.7%), CRF02_AG (57.1%) and unclassifiable, UG (7.1%). Major PI resistance-associated mutations were identified at two sites including M46L (16.7% of subtype G/UG) and V82L (6.3% of CRF02_AG). Minor PI resistance-associated mutations identified among subtype G/UG are L10V/I (8.3%) and K20I (100%) while L10V/I (50%), K20I (100%), L33F (6.3%) and N88D (6.3%) were identified among CRF02_AG. Other polymorphisms found include; I13V/A, E35Q, M36I/L, N37D/S/E/H, R57K/G, L63T/P/S/Q, C67E/S, H69K/R, K70R, V82I and L89M in the range of 28.6% to 100% among the different subtypes. Interpretation based on Stanford algorithm showed that Darunavir/ritonavir is the only regimen whose potency was not compromised by the circulating mutations. Identification of major and minor PI resistance mutations in this study underscores the need for drug resistance testing prior to initiation of second line antiretroviral therapy in Nigeria.

Early HIV infection is associated with reduced proportions of gamma delta T subsets as well as high creatinine and urea levels.

Renal dysfunctions are major predictors of co-morbidities and mortality in HIV-infected individuals. Unconventional T cells have been shown to regulate kidney functions. However, there is dearth of information on the effect of HIV-associated nephropathies on γδ and DN T cells. It is also not clear whether γδ T cell perturbations observed during the early stages of HIV infection occur before immune activation. In this study, we investigated the relationship between creatinine and urea on the number of unconventional T cells in HIV-infected individuals at the early and chronic stages of infection. Persons in the chronic stage of infection were divided into treatment naïve and exposed groups. Treatment exposed individuals were further subdivided into groups with undetectable and detectable HIV-1RNA in their blood. Creatinine and urea levels were significantly higher among persons in the early HIV infection compared with the other groups. Proportions of γδ T, γδ + CD8, γδ + CD16 cells were also significantly reduced in the early stage of HIV infection (P < .01). Markers of immune activation, CD4 + HLA-DR and CD8 + HLA-DR, were also significantly reduced during early HIV infection (P < .01). Taken together, our findings suggest that high levels of renal markers as well as reduced proportions of gamma delta T cells are associated with the early stages of HIV infection. This event likely occurs before systemic immune activation reaches peak levels. This study provides evidence for the need for early HIV infection diagnosis and treatment.

Low levels of HIV-1 drug resistance mutations in patients who achieved viral re-suppression without regimen switch: a retrospective study.

BACKGROUND: We identified a HIV-positive cohort in virologic failure (VF) who re-suppressed without drug switch. We characterized their drug resistance mutations (DRM) and adherence profiles to learn how to better manage HIV drug resistance. A retrospective cohort study utilizing clinical data and stored samples. Patients received ART at three Nigerian treatment centres. Plasma samples stored when they were in VF were genotyped. RESULT: Of 126 patients with samples available, 57 were successfully genotyped. From ART initiation, the proportion of patients with adherence ≥90% increased steadily from 54% at first high viral load (VL) to 67% at confirmed VF, and 81% at time of re-suppressed VL. Sixteen (28%) patients had at least one DRM. Forty-six (81%) patients had full susceptibility to the three drugs in their first-line (1 L) regimen. Thirteen (23%) were resistant to at least one antiretroviral drug but three were resistant to drugs not used in Nigeria. Ten patients had resistance to their 1 L drug(s) and six were fully susceptible to the three drugs in the recommended second-line regimen. CONCLUSION: This cohort had little drug resistance mutations. We conclude that if adherence is not assured, patients could exhibit virologic failure without having developed mutations associated with drug resistance.

Non-synonymous Substitutions in HIV-1 GAG Are Frequent in Epitopes Outside the Functionally Conserved Regions and Associated With Subtype Differences.

In 2019, 38 million people lived with HIV-1 infection resulting in 690,000 deaths. Over 50% of this infection and its associated deaths occurred in Sub-Saharan Africa. The West African region is a known hotspot of the HIV-1 epidemic. There is a need to develop an HIV-1 vaccine if the HIV epidemic would be effectively controlled. Few protective cytotoxic T Lymphocytes (CTL) epitopes within the HIV-1 GAG (HIV_gagconsv) have been previously identified to be functionally conserved among the HIV-1 M group. These epitopes are currently the focus of universal HIV-1 T cell-based vaccine studies. However, these epitopes' phenotypic and genetic properties have not been observed in natural settings for HIV-1 strains circulating in the West African region. This information is critical as the usefulness of universal HIV-1 vaccines in the West African region depends on these epitopes' occurrence in strains circulating in the area. This study describes non-synonymous substitutions within and without HIV_gagconsv genes isolated from 10 infected Nigerians at the early stages of HIV-1 infection. Furthermore, we analyzed these substitutions longitudinally in five infected individuals from the early stages of infection till after seroconversion. We identified three non-synonymous substitutions within HIV_gagconsv genes isolated from early HIV infected individuals. Fourteen and nineteen mutations outside the HIV_gagconsv were observed before and after seroconversion, respectively, while we found four mutations within the HIV_gagconsv. These substitutions include previously mapped CTL epitope immune escape mutants. CTL immune pressure likely leaves different footprints on HIV-1 GAG epitopes within and outside the HIV_gagconsv. This information is crucial for universal HIV-1 vaccine designs for use in the West African region.

Molecular characterisation of genital human papillomavirus among women in Southwestern, Nigeria.

BACKGROUND: Persistent infections with high-risk genital Human papillomavirus (HPV) especially types 16 and 18, are associated with cervical cancer. However, distribution of HPV types varies greatly across geographical regions and the available vaccines target only few types. This study was designed to determine the HPV types circulating in Southwestern Nigeria, thereby providing necessary information for effective control of the virus. METHODS: Endocervical swab samples were collected from a total of 295 consenting women attending routine cervical cancer screening, STI clinics and community-based outreach programme. Viral DNA was extracted from the samples and the consensus region of the HPV DNA was amplified by PCR using GP-E6/E7 primers. Type-specific nested multiplex PCR and Sanger sequencing were used to genotype the HPV isolates. RESULTS: In this study, 51 (17.3%) individuals were positive for HPV DNA using consensus primers that target the E6/E7 genes but only 48 (16.3%) were genotyped. A total of 15 HPV types (HPV-6, 16, 18, 31, 33, 35, 42, 43, 44, 52, 58, 66, 74, 81, 86) were detected, with HPV-31 being the most predominant (32.8%), followed by HPV-35 (17.2%) and HPV-16 (15.5%). Two rare HPV types; 74 and 86 were also detected. The HPV-74 isolate had three nucleotide (CCT) insertions at E7 gene that translated into amino acid proline. Highest nucleotide substitutions (n = 32) were found in HPV-44 genotype. Among positive individuals, 20.8% had dual infections and 86.2% had High-risk HPV types. CONCLUSIONS: Multiple Human papillomavirus types co-circulated in the study. Most of the circulating Human papillomavirus are high-risk type with type 31 being the most predominant. Although the implication of HPV-74 with proline insertion detected for the first time is unknown, it may have effect on the transformation potential of the virus. Polyvalent HPV vaccine will be more effective for the infection control in Nigeria.

Correction: Phylogenetic analysis of hepatitis C virus among HIV/ HCV co-infected patients in Nigeria.

[This corrects the article DOI: 10.1371/journal.pone.0210724.].

Phylogenetic analysis of hepatitis C virus among HIV/ HCV co-infected patients in Nigeria.

Hepatitis C virus (HCV) infection has been associated with liver disease including liver cirrhosis and hepatocellular carcinoma (HCC) in chronically-infected persons. However, in HIV/HCV co-infected patients, increased rate of progression to cirrhosis and HCC has been reported. Limited information exists regarding genetic variants of HCV circulating among co-infected patients, which could be important in the design of broadly protective vaccine and management of the disease. Here, we determined the genotypes of HCV isolates circulating among HIV/HCV co-infected patients in Ibadan, southwestern Nigeria. One hundred and twenty-five HIV/HCV IgM positive samples obtained from HIV laboratory, University of Ibadan were used for this study. HCV NS5B gene was amplified using polymerase chain reaction (PCR). The amplified NS5B gene was sequenced using gene specific primers. Twenty isolates were amplified, out of which 13 were successfully sequenced. Phylogenetic analysis of the 13 sequenced isolates showed three HCV subtypes 1a, 3a and 5a belonging to genotypes 1, 3 and 5 respectively. Ten isolates (77%) belong to subtype 5a, followed by 2 isolates (15%) subtype 1a and 1 isolate (8%) was subtype 3a. The predominant HCV genotype was 5, followed by genotype 1 (subtype 1a). The findings, as well as the observed mutations in NS5B gene, indicate the need for screening and monitoring of HIV/HCV co-infected patients. Further study to determine the phylogeny of isolates circulating in other parts of Nigeria will be carried out.

Virus genes and host correlates of pathology are markedly reduced during respiratory syncytial and influenza virus co-infection in BALB/c mice.

Globally, influenza A virus (IAV) and respiratory syncytial virus (RSV) infection remain very high. There is also a high burden of IAV and RSV co-infection in developing countries. To develop universally protective vaccines against these infections, it is imperative that viral genes and immune correlates of pathology are elucidated. As such, we profiled virus genes expressions, histopathology and immunological responses of BALB/c mice infected with RSV and/or IAV in this study. RSV A2 and/or influenza A/H3N2/Perth/16/09 (Pr/H3N2) were induced over a seven-day period in BALB/c mice. Anaesthetized BALB/c mice (12-14 g) were divided into six groups (15-20 mice per group), inoculated with 32 µl each of 3LD50 Pr/H3N2 and/or 100 TCID50 RSV. Two groups (R or I) received RSV or Pr/H3N2 intranasally. Prior infection with either RSV or Pr/H3N2 was followed with a second challenge of the other virus 24 hours post inoculation in RI and IR groups. Another set was exposed to the two viruses simultaneously (I + R group) while the last group served as healthy controls. Five to seven mice per group were euthanized at days 2, 4 and 7. Lung and spleen organs were harvested for virus genes quantitation and immune cells phenotyping respectively. I + R group showed progressive downregulation of RSV F, G, NS1 and NS2 genes. IAV PB2 and M genes had high fold increase on day 2 and 4 post infections. However, by day 7 post infection, M and PB2 fold increase was lower. Also, increased proportions of NKT and T cell subsets were observed throughout the period in I + R group. Conversely, I group was characterized by reduced NKT cell counts and enhanced CD8 T cells levels while R group only showed an increased proportion of CD8 T cells towards the peak of infection. This study shows that RSV and IAV co-infection lead to reduced virulence and pathology compared to single infections. This information is very useful in combinatorial RSV/IAV vaccine design and development.

Genetic diversity of human respiratory syncytial virus circulating among children in Ibadan, Nigeria.

Human respiratory syncytial virus (HRSV) is the most common viral cause of acute lower respiratory tract infections (LRTIs) in infants and young children however, without an effective vaccine licensed for human use till date. Information on the circulating genotypes of HRSV from regions with high-burden of infection is vital in the global efforts towards the development of protective vaccine. We report here the genotypes of HRSV circulating among children in Ibadan, the first of such from Nigeria.Nasopharyngeal and oropharyngeal swabs collected from 231 children presenting with respiratory infections in some health facilities for care as well as those attending immunization centers for routine vaccination in Ibadan, Nigeria were used for the study. The 2nd hypervariable (HVR2) region of the glycoprotein (G) gene of HRSV was amplified and sequenced using HRSV group specific primers. HRSV was detected in 41 out of the 231 samples. Thirty-three of the isolates were successfully subtyped(22 subtype A and 11 subtype B). Fourteen of the subtype A and all the subtype B were successfully sequenced and genotyped. Phylogenetic analysis showed that genotype ON1 with 72 nucleotide (nt) duplication was the major subgroup A virus (11 of 14) detected together with genotype NA2. All the HRSV subtype B detected belong to the BA genotype with characteristic 60nt duplication. The ON1 genotypes vary considerably from the prototype strain due to amino acid substitutions including T292I which has not been reported elsewhere. The NA2 genotypes have mutations on four antigenic sites within the HVR2relative to the prototype A2. In conclusion, three genotypes of HRSV were found circulating in Ibadan, Nigeria. Additional study that will include isolates from other parts of the country will be done to determine the extent of genotype diversity of HRSV circulating in Nigeria.

Early HIV infection among persons referred for malaria parasite testing in Nigeria.

Persons in the early stages of HIV infection are the major drivers of new infections. These individuals may also develop renal dysfunctions at this time. Nigeria, as other African countries, has one of the highest prevalence of newly diagnosed HIV infections. Despite this, limited information exists on early HIV detection in the continent. This may be related to difficulties in providing early HIV diagnosis and treatment. Patients referred for malaria testing may provide a unique opportunity for early HIV detection. In this study, a method for identifying early HIV-infected individuals was assessed. HIV-1 subtype and renal function biomarkers were also analyzed in these persons. To identify early HIV infection, over a period of 18 months blood samples were collected from persons referred by clinicians for malaria parasite tests in Nigeria. A total of 671 samples were collected and analyzed for HIV antigen/antibody and subtypes. 101 of these samples were categorized into one of four groups: early HIV, chronic HIV, malaria infection and control groups for renal function analysis. 29% of HIV infected individuals were at the early stages of infection. The predominant subtype detected was CRF02_AG (57.14%). The early HIV group had the highest mean serum creatinine (95 µmol/L) and urea (5.7 mmol/L) values across all groups with the difference significant at P < 0.05. There was no significant difference between the circulating subtype and the stage of HIV infection. Our results show the feasibility of screening persons referred for malaria tests for early HIV. This can be used to control new HIV infections in sub-Saharan Africa.

Implication of First-Line Antiretroviral Therapy Choice on Second-Line Options.

BACKGROUND: Although there are a number of studies comparing the currently recommended preferred and alternative first-line (1L) antiretroviral therapy (ART) regimens on clinical outcomes, there are limited data examining the impact of 1L regimen choice and duration of virologic failure (VF) on accumulation of drug resistance mutations (DRM). The patterns of DRM from patients failing zidovudine (AZT)-containing versus tenofovir (TDF)-containing ART were assessed to evaluate the predicted susceptibility to second-line (2L) nucleoside reverse-transcriptase inhibitor (NRTI) backbone options in the context of an ongoing programmatic setting that uses viral load (VL) monitoring. METHODS: Paired samples from Nigerian ART patients who experienced VF and switched to 2L ART were retrospectively identified. For each sample, the human immunodeficiency virus (HIV)-1 polymerase gene was sequenced at 2 time points, and DRM was analyzed using Stanford University's HIVdb program. RESULTS: Sequences were generated for 191 patients. At time of 2L switch, 28.2% of patients on AZT-containing regimens developed resistance to TDF, whereas only 6.8% of patients on TDF-containing 1L had mutations compromising susceptibility to AZT. In a stratified evaluation, patients with 0-6 months between tested VL samples had no difference in proportion compromised to 2L, whereas those with >6 months between samples had a statistically significant difference in proportion with compromised 2L NRTI. In multivariate analyses, patients on 1L AZT had 9.90 times higher odds of having a compromised 2L NRTI option than patients on 1L TDF. CONCLUSIONS: In the context of constrained resources, where VL monitoring is limited, we present further evidence to support use of TDF as the preferred 1L NRTI because it allows for preservation of the recommended 2L NRTI option.

Demographic and epidemiological characteristics of HIV opportunistic infections among older adults in Nigeria.

BACKGROUND: In view of the maturing HIV epidemic in sub-Saharan Africa, better understanding of its epidemiology among older adults is necessary in order to design appropriate care and treatment programmes for them. OBJECTIVES: To describe the demographic and epidemiological characteristics of HIV opportunistic infections among newly enrolled patients aged 50 years and above in Ibadan, South-West Nigeria. METHODS: Analysis of data extracted from electronic records of 17, 312 subjects enrolled for HIV/AIDS care and treatment between January 2006 and December 2014 at the ART clinic, University College Hospital, Ibadan. RESULTS: Age of the patients ranged from 18 to 90 years with a mean of 36.4 years (SD= 10.3) with older adults constituting 12.0% (2075). Among older adults, about half (52.9%) were females. Majority (59.1%) were currently married while 25.9% were widowed. Prevalence of opportunistic infections was 46.6%. The commonest opportunistic infections (OIs) were: oral candidiasis (27.6%), chronic diarrhoea (23.5% and peripheral neuropathy (14.8%). Significant factors associated with opportunistic infections in older adults were: CD4 count less than 350 (OR=3.12, CI: 2.29-4.25) and hepatitis C virus co-infection (OR=2.17, CI: 1.14-4.13). CONCLUSION: There is need for prompt response to the peculiar challenges associated with the emerging shift in the epidemiology of HIV and associated infections in sub-Saharan Africa.

Mechanistic perspective of the oxido-immunopathologic resolution property of kolaviron in mice influenza pneumonitis.

Implicated in influenza-associated pathology are innate defence overzealousness and unabated secretion of oxidative tissue-sensitive antimicrobial agents. At different time points, mice were pre-treated with kolaviron (400 mg/kg), a natural antioxidant and anti-inflammatory agent, and subsequently challenged with 2 LD50 influenza A/H3N2/Perth/16/09 virus. After euthanasia at day 6, blood, lungs, liver and spleen were collected and processed for biochemical, immunohistochemical and flow cytometric assessment of redo-inflammatory imbalance, cytokine storm indices and T helper 1 host response. Previously kolaviron was reported to delay mortality onset, improve morbidity and attenuate myeloperoxidase activity and nitric oxide production with minimal impact on viral clearance. This study additionally confirmed nitric oxide, but not hydrogen peroxide, as the major culprit implicated in influenza virus-induced oxido-pathology. Systemic effect of the sustained inflammation and nitrosative stress was more prominent in the spleen and lung than in the liver of mice infected with A/H3N2/Perth/16/09. Influential to immunopathology was heightened pulmonary expression of IL-1ß, RANTES, IL-10, MCP-1, NF-κB, iNOS and COX-2. However, kolaviron combated the influenza-established nitrative stress, reversed the elicited cytokine storm and restored the oxidized environment to a reductive milieu. Our data also suggest that kolaviron administration early in infection may foster CD4+ response. These data indicate that kolaviron may confer disease-dwindling properties during acute influenza infection via a system-wide protective approach involving multiple targets especially at the early stage of the infection.

Complete Genome Sequence of a Genotype XVII Newcastle Disease Virus, Isolated from an Apparently Healthy Domestic Duck in Nigeria.

The first complete genome sequence of a strain of Newcastle disease virus (NDV) of genotype XVII is described here. A velogenic strain (duck/Nigeria/903/KUDU-113/1992) was isolated from an apparently healthy free-roaming domestic duck sampled in Kuru, Nigeria, in 1992. Phylogenetic analysis of the fusion protein gene and complete genome classified the isolate as a member of NDV class II, genotype XVII.

Intestinal Bacterial Colonization in the First 2 Weeks of Life of Nigerian Neonates Using Standard Culture Methods.

OBJECTIVE: The pattern and timing of development of intestinal microflora in Nigerian infants have been scarcely researched. This study was carried out to investigate the bacteria flora in the rectum of healthy neonates in Ibadan, Nigeria. PATIENTS AND METHODS: In this hospital-based longitudinal study, rectal swabs of 70 neonates were taken within 6-12 h of birth (day 1) and subsequently on days 3, 9, and 14. Information collected included maternal sociodemographic characteristics, antibiotic use for the neonates, and type of feeding during the first 14 days of life. Identification and speciation of gram-negative isolates were done using the Analytical Profile Index 20E® and 20NE® as appropriate. Gram-positive bacteria were identified biochemically using the catalase and coagulase tests. Data were analyzed using descriptive statistics and Chi-square at p = 0.05. RESULTS: Majority (92.9%) of the neonates were delivered vaginally with a median gestational age of 38 weeks (range = 34-42). On the first day of life, Escherichia coli was isolated more frequently from the rectal swabs of preterm (50.0%) than term (23.1%) neonates (p = 0.031). On day 3 of life, coagulase-negative staphylococcus was the most frequently isolated bacteria from the rectal swabs of nonasphyxiated (64.4%) compared with asphyxiated (27.3%) neonates' rectal swabs (p = 0.042). Staphylococcus aureus was the most frequently isolated bacteria from the rectal swabs of nonexclusively breastfed (66.7%) than exclusively breastfed (21.3%) neonates on day 14 (p = 0.004). CONCLUSION: Staphylococcus aureus and Escherichia coli were the predominant isolates from the rectum of Nigerian neonates, and these isolates were influenced by breastfeeding and mild-moderate asphyxia. In all, bacterial diversity in the rectum increased as the neonates got older.

Temporal distribution of baseline characteristics and association with early mortality among HIV-positive patients at University College Hospital, Ibadan, Nigeria.

The first six months of HIV care and treatment are very important for long-term outcome. Early mortality (within 6 months of care initiation) undermines care and treatment goals. This study assessed the temporal distribution in baseline characteristics and early mortality among HIV patients at the University College Hospital, Ibadan, Nigeria from 2006-2013. Factors associated with early mortality were also investigated. This was a retrospective analysis of data from 14 857 patients enrolled for care and treatment at the adult antiretroviral clinic of the University College Hospital, Ibadan, Nigeria. Effects of factors associated with early mortality were summarised using a hazard ratio with a 95% confidence interval obtained from Cox proportional hazard regression models. The mean age of the subjects was 36.4 (SD=10.2) years with females being in the majority (68.1%). While patients' demographic characteristics remained virtually the same over time, there was significant decline in the prevalence of baseline opportunistic infections (2006-2007=55.2%; 2011-2013=38.0%). Overall, 460 (3.1%) patients were known to have died within 6 months of enrollment in care/treatment. There was no significant trend in incidence of early mortality. Factors associated with early mortality include: male sex, HIV encephalopathy, low CD4 count (< 50 cells), and anaemia. To reduce early mortality, community education should be promoted, timely access to care and treatment should be facilitated and the health system further strengthened to care for high risk patients.

Kolaviron Improves Morbidity and Suppresses Mortality by Mitigating Oxido-Inflammation in BALB/c Mice Infected with Influenza Virus.

Influenza A viruses (IAV) induce cytokine storm and host's intracellular redox imbalance to ensure continuous replication and survival, leading to severe immunopathology and death. The unpredictability of broad-spectrum vaccines, the emergence of drug-resistant and/or more virulent strains, the prevalence of the amantadane-resistant IAV, and the prohibitive cost of available drugs especially in resource-poor countries necessitate exploring drugs with novel action mechanisms as anti-influenza agents. This study presents the protective role of kolaviron (KV), a natural antioxidant and anti-inflammatory agent from Garcinia kola seeds, on BALB/c mice challenged with influenza A/Perth/H3N2/16/09 (Pr/H3N2) virus. KV at 400 mg/kg was administered orally to groups of BALB/c mice for 3 days, 3 h, and 1 h prior to infection with 1LD50 or 3LD50 (14-day study) and 5LD50 (6-day study) Pr/H3N2. Pr/H3N2 in the lungs was detected by hemagglutination assay, while oxidative stress and inflammatory biomarkers were assayed in both lungs and liver. Infected mice treated with KV progressively increased in weight with minimal mortality. Single-dose administration of KV at 1 h or 3 h before viral challenge and 3 days pretreatment improved lung aeration and reduced lung consolidation as well as inflammatory cells infiltration in a way that had minimal impact on viral clearance, but attenuated myeloperoxidase activity and nitric oxide production via priming of reduced glutathione levels, thus enhancing the preservation of function in the lungs and liver. This study suggests that KV may be effective for delaying the development of clinical symptoms of influenza virus, and this may be through a mechanism unrelated to those deployed by the existing anti-influenza drugs but closely associated to its antioxidant and immunomodulatory properties.

Temporal distribution of baseline characteristics and association with early mortality among HIV-positive patients at University College Hospital, Ibadan, Nigeria

The first six months of HIV care and treatment are very important for long-term outcome. Early mortality (within 6 months of care initiation) undermines care and treatment goals. This study assessed the temporal distribution in baseline characteristics and early mortality among HIV patients at the University College Hospital; Ibadan; Nigeria from 2006-2013. Factors associated with early mortality were also investigated. This was a retrospective analysis of data from 14 857 patients enrolled for care and treatment at the adult antiretroviral clinic of the University College Hospital; Ibadan; Nigeria. Effects of factors associated with early mortality were summarised using a hazard ratio with a 95% confidence interval obtained from Cox proportional hazard regression models. The mean age of the subjects was 36.4 (SD=10.2) years with females being in the majority (68.1%). While patients' demographic characteristics remained virtually the same over time; there was significant decline in the prevalence of baseline opportunistic infections (2006-2007=55.2%; 2011-2013=38.0%). Overall; 460 (3.1%) patients were known to have died within 6 months of enrollment in care/treatment. There was no significant trend in incidence of early mortality. Factors associated with early mortality include: male sex; HIV encephalopathy; low CD4 count ( 50 cells); and anaemia. To reduce early mortality; community education should be promoted; timely access to care and treatment should be facilitated and the health system further strengthened to care for high risk patients