Pre-existing immunity to SARS-CoV-2 before the COVID-19 pandemic era in Cameroon: A comparative analysis according to HIV-status

BackgroundThe lower burden of COVID-19 in tropical settings may be due to preexisting cross-immunity, which might vary according to geographical locations and potential exposure to other pathogens. We sought to assess the overall prevalence of SARS-CoV-2 antibodies and determine SARS-CoV-2 seropositivity according to HIV-status before the COVID-19 pandemic era. MethodsA cross-sectional and comparative study was conducted at the Chantal BIYA International Reference Centre (CIRCB) on 288 stored plasma samples (163 HIV-positive versus 125 HIV-negative); all collected in 2017-2018, before the COVID-19 pandemic era. Abbott Panbio (TM) COVID-19 IgG/IgM assay was used for detecting SARS-CoV-2 immunoglobulin G (IgG) and M (IgM). Among people living with HIV (PLHIV), HIV-1 viral load and TCD4 cell count (LTCD4) were measured using Abbott Real Time PCR and BD FACSCalibur respectively. Statistical analyses were performed, with pResultsThe median [IQR] age was 25 [15-38] years. Overall seropositivity to SARS-CoV-2 antibodies was 13.5% (39/288) of which 7.3% (21) was IgG, 7.3% (21) IgM and 1.0% (3) IgG/IgM. According to HIV-status in the study population, SARS-CoV-2 seropositivity was 11.0% (18/163) among HIV-positive versus 16.8% (21/125) among HIV-negative respectively, p=0.21. Specifically, IgG was 6.1% (10/163) versus 8.8% (11/125), p=0.26; IgM was 5.5% (9/163) versus 9.6%, (12/125), p=0.13 and IgG/IgM was 0.6% (1/163) versus 1.6% (2/125) respectively. Among PLHIV, SARS-CoV-2 seropositivity according to CD4 count was 9.2% (>= 500 cells/mu L) versus 1.8% (200-499 cells/mu L), (OR=3.5; p=0.04) and 0.6% (<200 cells/mu L), (OR=17.7; p<0.01). According to viral load, SARS-CoV-2 seropositivity was 6.7% (>= 40 copies/mL) versus 4.9% (<40 copies/mL), (OR= 3.8; p<0.01). ConclusionBefore COVID-19 in Cameroon, cross-reactive antibodies to SARS-CoV-2 were in circulation, indicating COVID-19 preexisting immunity. This preexisting immunity may contribute in attenuating disease severity in tropical settings like Cameroon. Of relevance, COVID-19 preexisting immunity is lower with HIV-infection, specifically with viral replication and poor CD4-cell count. As poor CD4-count leads to lower cross-reactive antibodies (regardless of viral load), people living with HIV appear more vulnerable to COVID-19 and should be prioritized for vaccination

Inflammatory profile of vertically HIV-1 infected adolescents receiving ART in Cameroon: a contribution toward optimal pediatric HIV control strategies

Antiretroviral therapy (ART) has improved the lifespan of people living with HIV. However, their immune system remains in a state of sustained activation/inflammation, which favors viral replication and depletion of helper T-cells with varying profiles according to ART-response. We herein sought to ascertain the inflammatory profile of adolescents living with perinatal HIV-1 infection (ALPHI) receiving ART in an African context. In this cross-sectional and comparative study among ART-experienced ALPHI in Yaoundé-Cameroon, HIV-1 RNA was measured by Abbott Real-time PCR; CD4 cells were enumerated using flow cytometry; serum cytokines were measured by ELISA; HIV-1 proviral DNA was genotyped by Sanger-sequencing; and archived drug resistance mutations (ADRMs) were interpreted using Stanford HIVdb.v9.0.1. Overall, 73 adolescents were enrolled (60 ALPHI and 13 HIV-1 negative peers) aged 15 (13-18) years; 60.00% were female. ART median duration was 92 (46-123) months; median viral load was 3.99 (3.17-4.66) RNA Log10 (copies)/mL and median CD4 count was 326 (201-654) cells/mm3. As compared to HIV-negative adolescents, TNFα was highly expressed among ALPHI (p<0.01). Following a virological response, inflammatory cytokines (IFNγ and IL-12), anti-inflammatory cytokines (IL-4 and IL-10) and inflammation-related cytokines (IL-6 and IL-1β) were highly expressed with viral suppression (VS) vs. virological failure (VF), while the chemokine CCL3 was highly expressed with VF (p<0.01). Regarding the immune response, the inflammatory cytokine TNFα was highly expressed in those that are immunocompetent (CD4≥500 cell/mm3) vs. immunocompromised (CD4<500 cell/mm3), p ≤ 0.01; while chemokine CCL2 was highly expressed in the immunocompromised (p<0.05). In the presence of ADRMs, IL-4 and CCL3 were highly expressed (p=0.027 and p=0.043 respectively). Among ART-experienced ALPHI in Cameroon, the TNFα cytokine was found to be an inflammatory marker of HIV infection; IFNγ, IL-1β, IL-6, and IL-12 are potential immunological markers of VS and targeting these cytokines in addition to antiretroviral drugs may improve management. Moreover, CCL3 and CCL2 are possible predictors of VF and/or being immunocompromised and could serve as surrogates of poor ART response

Genotypic resistance testing improves antiretroviral treatment outcomes in a cohort of adolescents in Cameroon: Implications in the dolutegravir‑era

Background: Acquired drug resistance (ADR) is common among adolescents living with perinatal HIV (APHI) in sub-Saharan Africa (SSA). Personalized management has the potential to improve pediatric antiretroviral therapy (ART), even in the presence of long-term treatment and HIV-1 subtype diversity. Objective: We sought to evaluate the effect of HIV-1 mutational profiling on immuno-virological response and ADR among APHI. Methods: A cohort-study was conducted from 2018-2020 among 311 APHI receiving ART in Cameroon. Clinical, immunological and virological responses were measured at enrolment (T1), 6-months (T2) and 12-months (T3). Immunological failure (IF: CD4<250 cells/mm3), VF (viremia≥1000 copies/ml), and ADR were analyzed, with p<0.05 considered significant. Results: Mean age was 15(±3) years; male-female ratio was 1:1; median [IQR] ART-duration was 36[21-81] months. At T1, T2, and T3 respectively, adherence-level was 66.4%, 58.3% and 66.5%; 14 viral clades were found, driven by CRF02_AG (58.6%); ADR-mutations favored increased switch to second-line ART (16.1%, 31.2%, and 41.9%, p<0.0001). From T1-T3 respectively, there were declining rates of IF (25.5%, 18.9%, and 9.83, p<0.0001), VF (39.7%, 39.9%, and 28.2%, p=0.007), and HIVDR (96.4%, 91.7%, and 85.0%, p=0.099). Predictors of ADR were being on first-line ART (p=0.045), high viremia at enrolment (AOR=12.56, p=0.059), and IF (AOR=5.86, p=0.010). Of note, optimized ART guided by mutational profile (AOR=0.05, p=0.002) was protective. Moreover, full Tenofovir+Lamivudine+Dolutegravir efficacy was predicted in 77% and 62% of APHI respectively after first- and second-line failure. Conclusions: Among APHI in this SSA setting, viral mutational profiling prompts the use of optimized Dolutegravir-based ART regimens, leading to improved immuno-virological response and declining ADR burdens. Thus, implementing personalized HIV medicine in this vulnerable population would substantially improve ART response and the achievement of the 95-95-95 goals in these underserved populations

Characterization of the Viral Reservoirs Among HIV-1 Non-B Vertically Infected Adolescents Receiving Antiretroviral Therapy: Protocol for an Observational and Comparative Study in Cameroon

BackgroundAntiretroviral therapy (ART) can bring HIV-1 levels in blood plasma to the undetectable level and allow a near-normal life expectancy for HIV-infected individuals. Unfortunately, ART is not curative and must be taken for life, because within a few weeks of treatment cessation, HIV viremia rebounds in most patients except for rare elite or posttreatment controllers of viremia. The primary source of this rebound is the highly stable reservoir of latent yet replication-competent HIV-1 proviruses integrated into the genomic DNA of the resting memory cluster of differentiation 4 (CD4+) T cells. To achieve a cure for HIV, understanding the cell reservoir environment is of paramount importance. The size and nature of the viral reservoir might vary according to the timing of therapy, therapeutic response, ART duration, and immune response. The mechanisms of reservoir maintenance generally depend on the levels/type of immune recognition; in addition, the dynamics of viral persistence are different between pediatric and adult populations. This difference could become more evident as children grow toward adolescence. ObjectiveWe aim to characterize the HIV reservoirs and their variability as per the virological and immunological profiles of HIV-1 non-B vertically infected adolescents receiving ART in Cameroon during the Adolescents' Viral Reservoirs study to provide accurate and reliable data for HIV cure research. MethodsThis study will involve HIV-1 non-B vertically infected adolescents selected from an existing cohort in our institution. Blood samples will be collected for analyzing immunological/virological profiles, including CD4/CD8 count, plasma viral load, immune activation/inflammatory markers, genotyping, and quantification of HIV-1 viral reservoirs. We will equally recruit an age-matched group of HIV-negative adolescents as control for immunological profiling. ResultsThis study received funding in November 2021 and was approved by the national institutional review board in December 2021. Sample collection will start in November 2022, and the study will last for 18 months. The HIV-1 sequences generated will provide information on the circulating HIV-1 subtypes to guide the selection of the most appropriate ART for the participants. The levels of immune biomarkers will help determine the immune profile and help identify factors driving persistent immune activation/inflammation in HIV-infected adolescents compared to those in HIV-uninfected adolescents. Analysis of the virological and immunological parameters in addition to the HIV-1 reservoir size will shed light on the characteristics of the viral reservoir in adolescents with HIV-1 non-B infection. ConclusionsOur findings will help in advancing the knowledge on HIV reservoirs, in terms of size and genetic variability in adolescents living with HIV. Such evidence will also help in understanding the effects of ART timing and duration on the size of the reservoirs among adolescents living with HIV—a unique population from whom the findings generated will largely contribute to designing functional cure strategies. International Registered Report Identifier (IRRID)PRR1-10.2196/4147

Correlation between the immuno-virological response and the nutritional profile of treatment-experienced HIV-infected patients in the East region of Cameroon.

BackgroundHIV management remains concerning and even more challenging in the frame of comorbidities like malnutrition that favors disease progression and mortality in resource-limited settings (RLS).ObjectiveTo describe the nutritional parameters of antiretroviral therapy (ART) recipients (without nutritional support) with respect to CD4 count and virological failure.MethodsA cross-sectional study was conducted from October to December 2018 among 146 consenting participants enrolled in two health facilities of the East-Region of Cameroon. Socio-demographic data, basic clinical information and treatment history were collected; blood samples were collected by venipuncture for laboratory analysis (HIV-1 viral load, CD4 Tcells measurement and biochemical analysis) performed at the "Chantal Biya" International Reference Center", Yaounde, Cameroon. The nutritional profile was assessed by using anthropometric and biochemical parameters. Data were analyzed using Excel 2016, Graph pad prism version 6; Spearman correlation and Kruskal-Wallis test were used; with pResultsMedian [IQR] age was 42 [33-51] years, 76.0% (111/146) were female and median [IQR] duration on ART was 54 [28-86] months. Of these participants, 11.6% (17/146) were underweight based on the body mass index and 4.7% (7/146) were at the stage of advanced weight loss. According to immunovirological responses, 44.5% (65/146) were immunocompromised (CD4ConclusionIn this RLS, with patients having about five years of ART-experience, malnutrition appears to be driven mainly by a poor BMI, indicating that about one of ten patients falls within this severe condition. However, the largely normal nutritional profiles should be interpreted with caution, considering local realities and food support programs in place. The present outcomes highlight the need for monitoring nutritional status of people receiving ART in RLS, toward the design of optimal food interventions

The mother-to-child transmission of HIV-1 and profile of viral reservoirs in pediatric population: A systematic review with meta-analysis of the Cameroonian studies.

BackgroundThe mother-to-child transmission of HIV-1 (MTCT) remains on the major route of HIV-transmission among pediatric populations in Africa. Though a prevention of MTCT (PMTCT) high-priority country, data on the MTCT burdens in Cameroon remains fragmented.ObjectiveWe sought to assess the pooled MTCT rate, its risk-factors, and to characterize viral reservoirs of infected-children in Cameroon.MethodsAll relevant observational cohort and cross-sectional studies conducted in Cameroon were searched from PubMed, African Journals Online, Google scholar, ScienceDirect and academic medical education databases. Heterogeneity and publication bias were respectively assessed by the I2 statistic and the Egger/funnel plot test. Meta-analysis was performed using the random effects model. MTCT rate >5% was considered as "high". This review was registered in the Prospero database, CRD42021224497.ResultsWe included a total of 29 studies and analyzed 46 684 children born from HIV-positive mothers. The overall rate of MTCT was 7.00% (95% CI = 6.07-8.51). According to regions, the highest burden was in Adamaoua-region (17.51% [95% CI:14.21-21.07]) with only one study found. PMTCT option-B+ resulted in about 25% reduction of MTCT (8.97% [95% CI: 8.71-9.24] without option-B+ versus 2.88% [95% CI: 5.03-9.34] with option-B+). Regarding risk-factors, MTCT was significantly associated with the absence of PMTCT-interventions both in children (OR:5.40 [95% CI: 2.58-11.27]) and mothers (OR: 3.59 [95% CI: 2.15-5.99]). Regarding viral reservoirs, a pro-viral DNA mean of 3.34±1.05 log10/mL was observed among 5/57 children and archived HIV drug resistance mutations were identified in pro-viral DNA marker among 21/79 infected-children.ConclusionIn spite of the dropdown in MTCT following option-B+ implementation, MTCT remains high in Cameroon, with substantial disparities across regions. Thus, in this era of option-B+, achieving MTCT elimination requires interventions in northern-Cameroon. The variation in pro-viral load in infected-children underlines the relevance of characterizing viral reservoirs for possible infection control in tropical settings

Systematic review and meta-analysis of the epidemiology of Lassa virus in humans, rodents and other mammals in sub-Saharan Africa.

Accurate data on the Lassa virus (LASV) human case fatality rate (CFR) and the prevalence of LASV in humans, rodents and other mammals are needed for better planning of actions that will ultimately reduce the burden of LASV infection in sub-Saharan Africa. In this systematic review with meta-analysis, we searched PubMed, Scopus, Africa Journal Online, and African Index Medicus from 1969 to 2020 to obtain studies that reported enough data to calculate LASV infection CFR or prevalence. Study selection, data extraction, and risk of bias assessment were conducted independently. We extracted all measures of current, recent, and past infections with LASV. Prevalence and CFR estimates were pooled using a random-effect meta-analysis. Factors associated with CFR, prevalence, and sources of between-study heterogeneity were determined using subgroup and metaregression analyses. This review was registered with PROSPERO, CRD42020166465. We initially identified 1,399 records and finally retained 109 reports that contributed to 291 prevalence records from 25 countries. The overall CFR was 29.7% (22.3-37.5) in humans. Pooled prevalence of LASV infection was 8.7% (95% confidence interval: 6.8-10.8) in humans, 3.2% (1.9-4.6) in rodents, and 0.7% (0.0-2.3) in other mammals. Subgroup and metaregression analyses revealed a substantial statistical heterogeneity explained by higher prevalence in tissue organs, in case-control, in hospital outbreak, and surveys, in retrospective studies, in urban and hospital setting, in hospitalized patients, and in West African countries. This study suggests that LASV infections is an important cause of death in humans and that LASV are common in humans, rodents and other mammals in sub-Saharan Africa. These estimates highlight disparities between sub-regions, and population risk profiles. Western Africa, and specific key populations were identified as having higher LASV CFR and prevalence, hence, deserving more attention for cost-effective preventive interventions

Current knowledge of human Mpox viral infection among healthcare workers in Cameroon calls for capacity-strengthening for pandemic preparedness

IntroductionAn increased incidence of human Monkeypox (Mpox) cases was recently observed worldwide, including in Cameroon. To ensure efficient preparedness and interventions in the health system, we sought to assess the knowledge of Mpox's transmission, prevention, and response among healthcare workers (HCWs) in Cameroon.MethodsA cross-sectional online survey was conducted among HCWs in Cameroon using 21-item questions adapted from the United States Centers for Disease Control and Prevention (US-CDC) standard questionnaire on Mpox. The overall knowledge of Mpox was assessed by cumulative score and categorized as excellent (≥80%, 17/21) or good (≥70%, ≥15/21) knowledge. The regression analysis was used to identify the predictors of Mpox knowledge.ResultsThe survey enrolled 377 participants, but only responses from 342 participants were analyzed. Overall, 50.6% were female participants, and 59.6% aged 30 years or younger. The majority of the participants were medical doctors (50.3%); most worked in central-level hospitals (25.1%) and had 1–5 years of experience (70.7%). A total of up to 92.7% were aware of Mpox, with social media (58.7%) and radio/television (49.2%) as the main sources. The mean knowledge score was 14.0 ± 3.0 (4 to 20), with only 12.9% having excellent knowledge (≥80%) and 42.1% having good knowledge of Mpox. Younger age (26–30 years old) was associated with good knowledge, while workplace type was associated with excellent knowledge of Mpox (aOR [95% CI]: 4.01 [1.43–11.24]). Knowledge of treatment/management of Mpox was generally poor across the different professional categories.ConclusionKnowledge of Mpox among HCWs is substandard across different professionals. Thus, for optimal preparedness and immediate interventions for Mpox and similar emerging pathogens, capacity-strengthening programs should be organized for HCWs while encouraging scientific literature and organizational social media websites

Evaluation of Circulating and Archived HIV-1 Integrase Drug-Resistance Variants among Patients on Third-Line ART in Cameroon: Implications for Dolutegravir-Containing Regimens in Resource-Limited Settings

We described the analysis of the genotypes of the population within third-line antiviral therapy in Cameroon, with a focus on defining the effects of prior raltegravir (RAL) treatment and resistance mutations for current dolutegravir (DTG) treatment. While supporting the current transition to DTG-containing ART in resource-limited settings toward the achievement of the UNAIDS' goal of HIV elimination by 2030, our findings suggested that RAL-exposed patients may need a specific monitoring approach either in a stratified or personalized model of third-line ART to ensure the long-term success of DTG-containing regimens.To ensure the long-term efficacy of dolutegravir (DTG), we evaluated the genotypic profile in viral reservoirs among patients on third-line (3L) antiretroviral therapy (ART) in Cameroon, according to prior exposure to raltegravir (RAL). A facility-based study was conducted from May through December 2021 among patients on 3L ART from HIV treatment centers in Yaounde and Douala. Viral load was measured, and genotyping was performed on plasma RNA and proviral DNA. HIV-1 drug resistance mutations were interpreted using HIVdb.v9.1 and phylogeny analysis was performed using MEGA.v7, with P &lt; 0.05 considered significant. Of the 12,093 patients on ART, 53 fully met our inclusion criteria. The median (IQR) age was 51 years (40 to 55 years), and the male/female ratio was 4/5. The median duration on integrase strand-transfer inhibitors (INSTI)-containing regimens was 18 months (12 to 32 months), and 15.09% (8/53) were exposed to RAL. The most administered 3L ART was TDF+3TC+DTG+DRV/r (33.96%, 18/53). Only 5.66% (3/53) had unsuppressed viremia (&gt;1000 copies/mL). Resistance testing in proviral DNA was successful for 18/22 participants and revealed 1/18 patients (5.56%, in the RAL-arm) with archived mutations at major resistance positions (G140R and G163R). Five subtypes were identified, CRF02_AG (12/18), CRF22_01AE (3/18), A1 (1/18), G (1/18), and F2 (1/18). In Cameroon, 3L-experienced patients had a good virological response with a low level of archived mutations in the integrase. This finding underscored the use of DTG-containing ART for heavily treated patients in similar programmatic settings. However, patients with prior exposure to RAL should be closely monitored following a stratified or personalized approach to mitigate risks of INSTI-resistance, alongside pharmacovigilance. IMPORTANCE We described the analysis of the genotypes of the population within third-line antiviral therapy in Cameroon, with a focus on defining the effects of prior raltegravir (RAL) treatment and resistance mutations for current dolutegravir (DTG) treatment. While supporting the current transition to DTG-containing ART in resource-limited settings toward the achievement of the UNAIDS' goal of HIV elimination by 2030, our findings suggested that RAL-exposed patients may need a specific monitoring approach either in a stratified or personalized model of third-line ART to ensure the long-term success of DTG-containing regimens