Browsing by Author "Ikomey, George Mondinde"

Now showing 1 - 9 of 9
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    Analyses of HIV-1 integrase sequences prior to South African national HIV-treatment program and availability of integrase inhibitors in Cape Town, South Africa
    (Nature Publishing Group, 2018) Brado, Dominik; Obasa, Adetayo Emmanuel; Ikomey, George Mondinde; Cloete, Ruben; Singh, Kamalendra; Engelbrecht, Susan; Neogi, Ujjwal; Jacobs, Graeme Brendon
    ENGLISH ABSTRACT: HIV-Integrase (IN) has proven to be a viable target for highly specific HIV-1 therapy. We aimed to characterize the HIV-1 IN gene in a South African context and identify resistance-associated mutations (RAMs) against available first and second generation Integrase strand-transfer inhibitors (InSTIs). We performed genetic analyses on 91 treatment-naïve HIV-1 infected patients, as well as 314 treatment-naive South African HIV-1 IN-sequences, downloaded from Los Alamos HIV Sequence Database. Genotypic analyses revealed the absence of major RAMs in the cohort collected before the broad availability of combination antiretroviral therapy (cART) and INSTI in South Africa, however, occurred at a rate of 2.85% (9/314) in database derived sequences. RAMs were present at IN-positions 66, 92, 143, 147 and 148, all of which may confer resistance to Raltegravir (RAL) and Elvitegravir (EVG), but are unlikely to affect second-generation Dolutegravir (DTG), except mutations in the Q148 pathway. Furthermore, protein modeling showed, naturally occurring polymorphisms impact the stability of the intasome-complex and therefore may contribute to an overall potency against InSTIs. Our data suggest the prevalence of InSTI RAMs, against InSTIs, is low in South Africa, but natural polymorphisms and subtype-specific differences may influence the effect of individual treatment regimens.
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    Chronic obstructive pulmonary disease (COPD) : neutrophils, macrophages and lymphocytes in patients with anterior tuberculosis compared to tobacco related COPD
    (BioMed Central, 2018-03-27) Guiedem, Elise; Ikomey, George Mondinde; Nkenfou, Celine; Walter, Pefura-Yone Eric; Mesembe, Martha; Chegou, Novel N.; Jacobs, Graeme Brendon; Okomo Assoumou, Marie Claire
    Objective: The inflammatory profile of chronic obstructive pulmonary disease (COPD) related to tobacco is known in certain studies while that of the post tuberculosis form is not yet known. This study aimed to evaluate the levels of neutrophils, macrophages and lymphocytes cells in sputum of COPD patients with history of smoking or anterior tuberculosis. Enumeration of cells in samples was analyzed using standard microscopy. Results: We enrolled 92 participants, 46 (50%) were COPD subjects comprising 22 (47.83%) smokers and 24 (52.17%) with anterior tuberculosis while 46 (50%) healthy persons constituted the control group. The levels of neutrophils, lymphocytes and monocytes were statistically higher in COPD patients compared to the control group with p-values of 0.0001 respectively. Neutrophils levels were higher in COPD patients with history of tobacco than in COPD patients with anterior tuberculosis with a mean rate of 4.72 × 106/ml and 2.48 × 106/ml respectively (p = 0.04). The monocytes and lymphocytes levels were not statistically different between the two sub-groups of COPD patients with p-value of 0.052 and 0.91 respectively. Neutrophils are the only inflammatory cells that were significantly higher in COPD patients with history of smoking as compared to COPD patients with anterior tuberculosis.
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    Cytokine profile in the sputum of subjects with post-tuberculosis airflow obstruction and in those with tobacco related chronic obstructive pulmonary disease
    (BioMed Central, 2020-10-01) Guiedem, Elise; Pefura-Yone, Eric Walter; Ikomey, George Mondinde; Nkenfou, Celine Nguefeu; Mesembe, Martha; Yivala, Mbanyamsig Mispa; Chendi, Bih Hycenta; Jacobs, Graeme Brendon; Chegou, Novel Njweipi; Okomo, Marie Claire Assoumou
    Background: Previous studies have shown that tuberculosis (TB) is a risk factor for chronic airflow limitation. Chronic obstructive pulmonary disease (COPD) is recognized as the result of chronic inflammation, usually related to noxious particles. Post-TB airflow obstruction and tobacco-related COPD have the same functional pathway characterized by persistent airflow limitation. We sought to compare the profile of 29 cytokines in the sputum of subjects with post-TB airflow obstruction and those with COPD related to tobacco. Results: The forced expiratory volume in the first second (FEV1) and forced expiratory volume/forced vital capacity (FEV/FVC) ratio were lower in the COPD patients with the history of smoking compared to the post-TB airflow obstruction subgroup. The stages of the disease were more advanced in COPD / tobacco patients. Among the cytokines, IL-1α, IL-1β, MIP-1β, sCD40L and VEGF levels were higher in COPD patients, compared to the controls with p values of 0.003, 0.0001, 0.03, 0.0001 and 0.02 respectively. When the two COPD subgroups were compared, IL-1α, IL-6, TNF-α and IL-8 levels were higher in the COPD patients with the history of tobacco compared to the COPD patients with the history of TB with p-values of 0.031, 0.05, 0.021 and 0.016, respectively. Conclusion: COPD related to tobacco is more severe than post-TB airflow obstruction. The pathogenesis of post-TB airflow obstruction appears to involve the cytokines IL-1RA, IL-1α, IL-1β, IL-17, GRO and sCD40L, while COPD related to tobacco involves more cytokines.
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    The disproportionate effect of COVID-19 mortality on ethnic minorities : genetics or health inequalities?
    (Elsevier, 2020) El-Khatib, Ziad; Jacobs, Graeme Brendon; Ikomey, George Mondinde; Neogi, Ujjwal
    The cases of novel coronavirus disease 2019 (COVID-19) continue to increase across the world, infecting nearly 5.5 million individuals and more than 350,000 death. The earlier studies indicate that significant risk factors for severe COVID-19 are older adults, and people with co-morbidities (regardless of age) including chronic lung diseases, heart diseases, severe obesity (body mass index 40 or higher), and diabetes. When it comes to the role of race/ethnicity, the data is limited, which could be disproportionately affecting ethnic minorities as observed in England during 2009 Influenza A (H1N1) pandemic [1 ]. Earlier reports from the United Kingdom indicated black, Asian and minority ethnic (BAME) are the hardest hit with COVID-19 both in terms of critically ill as well as higher mortality [2 ]
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    Evidence of co and triple infections of Hepatitis B and C amongst HIV infected pregnant women in Buea, Cameroon
    (Science Publishing Group, 2016-03) Ikomey, George Mondinde; Jacobs, Graeme Brendon; Tanjong, Becky; Mesembe, Martha Tongo; Eyoh, Agnes; Lyonga, Emilia; Mfoataw, Ebot; Ngoh, Rose; Tamandjou Tchuem, Cynthia Raissa; Ikomey, Greg; Okomo Assoumou, Marie Claire
    Little epidermiological data is available on the prevalence of HIV, Hepatitis B and C, Co-and or triple infection during pregnancy in Cameroon as well as many other resource limited settings. HIV and Hepatitis B and C are major public health concerns world wide. Our study aimed at assessing the seroprevalence of Hepatitis B and C amongst HIV infected pregnant women in Buea, located in the Southwest region of Cameroon. A Cross-sectional study on consented pregnant women were conducted from March 2015 to August 2015. HIV-1 infections were detected using the national HIV-1 test algorithms. Hepatitis B surface antigen (HBsAg), anti-HBe and anti- Hepatitis C (anti-HCV) were detected using Enzyme linked Immunosorbent Assays (ELISAs). Of the 1230 recruited pregnant women, 97/1230 (7.8%) (95% CI: 3.5, 29.0%) were confirmed HIV-1 positive. HIV/HBV co-infection were observed in 14/97 (14.4%) (95% CI: 39.8, 100%), whilst 11/97 (11.3 %; 95% CI: 27.5, 100%) were HIV/HCV co-infections. Two HIV-infected pregnant women (8/97(8.2%; 95% CI: 0.1, 17.2%)) were HIV/HBV/HCV triple-infected. Anti-HBc was detected in all HBV-infected pregnant women (14/14; (100.0%)) (95.0% CI: 39.8, 100.0%). Seropositivity for HIV-1 was higher (37%) amongst subjects aged between 32-37 years, whilst none was found above 40. From our results we conclude that Co- and triple infections of HIV, Hepatitis B and C were present amongst pregnant women in Buea. Epidemiological data generated from this study are limited due to the existence of triple infected. It will therefore serve as a guide to the government policies to reinforce screening, treatment and prevention strategies, through its Mother–to-Child–transmission (pMTCT) Programme nationwide.
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    Fas mediated(CD95L) periferal T-cell Apotosis marker in monitoring HIV-1 disease progression in adults in Yaoundé, Cameroon
    (Science Publishing Group, 2016-03-22) Ikomey, George Mondinde; Julius, Atashili; Jacobs, Graeme Brendon; Mesembe, Martha Tongo; Eyoh, Agnes; Lyonga, Emilia; Claire, Okomo Assoumou Marie; Pathology: Medical Virology
    sFas (CD95) / FasL are hallmarks of apoptosis involvement in pathogenesis of HIV. We assess changes in soluble Fas /FasL, CD4 % and HIV-1 viral load in patients prior to the initiation of antiretroviral therapy (ART) and 6 months thereafter. A prospective longitudinal study on sixty consented HIV-1 positive adults. sFas and sFasL levels were measured by ELISA. CD4 cell counts and HIV-1 viralloads were measured using standard methods. Samples were analysed according to the manufacturers’ guidelines.There was a significant positive correlation between HIV-1 viral load and FasL at six months (M6) on treatment [r = +0.49, (0.03)]. There were no correlation between sFas/FasL and CD4 cell counts [ r = -33 (0.16), -31 (0.17) - 23 (0.03) respectively]. The significant correlation between sFasL and HIV-1 viral load at six months of ART suggests that sFasL could be a signal biomarker for HIV-1 disease progression. We have shown in this study that high levels of sFasL depict high HIV-1 viral loads and advance state of the HIV disease. These biomarker should be investigated further in other settings.
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    Observed HIV drug resistance associated mutations amongst naïve immunocompetent children in Yaounde, Cameroon
    (European HIV/AIDS and Infectious Diseases Academy, 2017) Ikomey, George Mondinde; Assoumou, Marie Claire Okomo; Gichana, Josiah Otwoma; Njenda, Duncan; Mikasi, Sello Given; Mesembe, Martha; Lyonga, Emilia; Jacobs, Graeme Brendon
    Introduction: The emergence of drug resistance mutations (DRMs) has been a major threat for successful lifelong combination antiretroviral therapy (cART), especially for HIV-vertically infected children within the context of the prevention of mother-to-child transmission (PMTCT). This study aimed to evaluate DRMs amongst immune competent treatment-naïve children in Cameroon. Methods: A cross-sectional study was conducted between 2015 and 2016 amongst 55 proxy consented HIV-1 positive children, aged 9 months to 6 years. They were all immune competent, cART naïve and with unknown history of PMTCT. CD4 cell counts and genotypic drug resistance testing were performed using standard methods. Results: Levels of DRMs to protease (PR) inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs were 27.6%, 3.7% and 40.7%, respectively. Only minor DRMs were observed for PR. The observed mutations for NRTI were K65R, T215I and K219E (33.0% each) and for NNRTI: V106M, Y181C and Y188H (6.0% each). Only minor accessory mutations were found in the integrase (IN) region. Conclusion: Despite widely available cART we still observe naïve HIV children, especially from the rural communities. We observe that a proportion of study participants had HIV-1 drug resistance associated mutations (RAMs). Data generated could help strengthen the current PMTCT programmes within the country. There is a need to upscale approaches for drug resistance testing for children in Cameroon and many other resource-limited settings.
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    Rate of viral load change and adherence of HIV adult patients treated with Efavirenz or Nevirapine antiretroviral regimens at 24 and 48 weeks in Yaounde, Cameroon : a longitudinal cohort study
    (BMC (part of Springer Nature), 2019) Chendi, Bih Hycenta; Assoumou, Marie Claire Okomo; Jacobs, Graeme Brendon; Yekwa, Elsie Laban; Lyonga, Emilia; Mesembe, Martha; Eyoh, Agnes; Ikomey, George Mondinde
    Background: HIV-load decrease and suppression over time is associated with consistent adherence to antiretroviral therapy (ART). Our study aimed to evaluate the difference in viral load and adherence of patients treated with a combination of either Tenofovir (TDF), Lamivudine (3TC) and Efavirenz (EFV) or TDF / Zidovudine (AZT), 3TC and Nevirapine (NVP) regimens at 24 and 48 weeks. Methods: A longitudinal study was conducted from May 2016 to June 2017 among 256 HIV infected adult patients who were enrolled at two approved treatment hospitals in Yaoundé, before the start of first-line ART. Whole blood samples were collected using standard operating procedures. HIV-loads were determined by a quantitative RealTime PCR assay. Adherence was evaluated by pharmacy refill data records. Statistical analyses were performed using the PRISM 5.0 software. Results: Off the 256 HIV infected patients enrolled, 180 (70%) patients completed the study and 76 (30%) patients were lost to follow-up. The success rate in achieving viral load < 40 copies/ml was 1.8 times higher with the EFV regimen at 24 weeks and was 1.2 times higher in the NVP regimen at 48 weeks. At 48 weeks the treatment failure rate was 12.0 and 40.0% in patients on EFV and the NVP regimen, respectively. The rate of adherence varied in both ART based regimens with 84.0 to 74.0% for EFV and 65.5 to 62.5% for NVP, at 24 and 48 weeks respectively. Conclusion: In our study and setting, the rate of viral load decrease was higher in the NVP based regimen than with the EFV regimen. The adherence rate to ART was higher in the EFV regimen, compared to the NVP regimen. This adds to evidence that the EFV regimen is the preferred ART combination for non-nucleoside reverse transcriptase inhibitors (NNRTIs).
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    Structural comparison of diverse HIV-1 subtypes using molecular modelling and docking analyses of integrase inhibitors
    (MDPI, 2020-08-26) Isaacs, Darren; Mikasi, Sello Given; Obasa, Adetayo Emmanuel; Ikomey, George Mondinde; Shityakov, Sergey; Cloete, Ruben; Jacobs, Graeme Brendon
    ENGLISH ABSTRACT: The process of viral integration into the host genome is an essential step of the HIV-1 life cycle. The viral integrase (IN) enzyme catalyzes integration. IN is an ideal therapeutic enzyme targeted by several drugs; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG), and bictegravir (BIC) having been approved by the USA Food and Drug Administration (FDA). Due to high HIV-1 diversity, it is not well understood how specific naturally occurring polymorphisms (NOPs) in IN may affect the structure/function and binding affinity of integrase strand transfer inhibitors (INSTIs). We applied computational methods of molecular modelling and docking to analyze the effect of NOPs on the full-length IN structure and INSTI binding. We identified 13 NOPs within the Cameroonian-derived CRF02_AG IN sequences and further identified 17 NOPs within HIV-1C South African sequences. The NOPs in the IN structures did not show any differences in INSTI binding affinity. However, linear regression analysis revealed a positive correlation between the Ki and EC50 values for DTG and BIC as strong inhibitors of HIV-1 IN subtypes. All INSTIs are clinically effective against diverse HIV-1 strains from INSTI treatment-naïve populations. This study supports the use of second-generation INSTIs such as DTG and BIC as part of first-line combination antiretroviral therapy (cART) regimens, due to a stronger genetic barrier to the emergence of drug resistance.