Characterization of HIV-1 Reservoirs in Children and Adolescents: A Systematic Review and Meta-Analysis Toward Pediatric HIV Cure.

OBJECTIVE: To conduct a comprehensive, systematic review of the profile of HIV-1 reservoirs in children and adolescents with perinatally acquired HIV infection. STUDY DESIGN: Randomized and nonrandomized trials, cohort studies, and cross-sectional studies on HIV reservoirs in pediatric populations, published between 2002 and 2022, were included. Archived-drug resistance mutations (ADRMs) and the size of reservoirs were evaluated. Subgroup analyses were performed to characterize further the data, and the meta-analysis was done through random effect models. RESULTS: Overall, 49 studies from 17 countries worldwide were included, encompassing 2356 perinatally infected participants (48.83% females). There are limited data on the quantitative characterization of viral reservoirs in sub-Saharan Africa, with sensitive methodologies such as droplet digital polymerase chain reaction rarely employed. The overall prevalence of ADRMs was 37.80% (95% CI 13.89-65.17), with 48.79% (95% CI 0-100) in Africa, 42.08% (95% CI 6.68-82.71) in America, 23.88% (95% CI 14.34-34.90) in Asia, and 20.00% (95% CI 10.72-31.17) in Europe, without any difference between infants and adolescents (P = .656). Starting antiretroviral therapy (ART) before 2 months of age limited the levels of HIV-1 DNA (P = .054). Participants with long-suppressed viremia (>5 years) had lower levels of HIV-1 DNA (P = .027). Pre- and post-ART CD4 ≤29% and pre-ART viremia ≥5Log were all found associated with greater levels of HIV-1 DNA (P = .038, P = .047, and P = .041, respectively). CONCLUSIONS: The pooled prevalence of ADRMs is high in perinatally infected pediatric population, with larger proviral reservoir size driven by delayed ART initiation, a shorter period of viral suppression, and immunovirological failures. Thus, strategies for pediatric HIV functional cure should target children and adolescents with very early ART initiation, immunocompetence, and long-term viral suppression.

Evaluation of archived drug resistance mutations in HIV-1 DNA among vertically infected adolescents under antiretroviral treatment in Cameroon: Findings during the COVID-19 pandemic.

BACKGROUND: With the success of antiretroviral therapy (ART), children born with HIV are more likely to reach adolescence. However, frequent non-adherence to ART in adolescents living with HIV (ALHIV) leads to viral replication. Notably, a viraemic infection might lead to archived drug resistance mutations (ADRMs). Hence, within the context of the COVID-19 pandemic, we aimed to compare the patterns of ADRMs in viraemic and non-viraemic vertically infected ALHIV and to assess their immunity to and diagnosis of SARS-CoV-2. METHODS: A comparative study was conducted among COVID-19-unvaccinated ALHIV receiving ART in Yaoundé-Cameroon over the period October 2021 to March 2022. Plasma HIV-RNA was measured using Abbott® m2000rt; HIV-1 genotyping was performed on buffy-coat (HIV-1 DNA) and ADRMs were interpreted using HIVdb.v9.0.1. Patterns of HIV-1 ADRMs were compared between viraemic (≥ 1.60 log10 HIV-1 RNA copies/ml) and non-viraemic (< 1.60 log10 copies/ml) individuals. SARS-CoV-2 antibodies were assessed on whole blood using Abbott Panbio COVID-19 immunoglobulin G/M (IgG/IgM) rapid test and COVID-19 polymerase chain reaction test was performed using nasopharyngeal swab samples. RESULTS: Of the 60 ALHIV [aged 17 (16-19) years, 51.6% female], median ART duration was 14 (12-16) years; 31/55 (56.3%) were exposed to nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART (of whom 19/31 transitioned to dolutegravir-based ART in 2020) and 24/55 (43.6%) were on second-line ART. Forty-two out of 60 (70.0%) ALHIV were non-viraemic; 43/60 (71.6%) were successfully sequenced. Overall the ADRM rate was 62.7% (27/43), with 69.2% (9/13) viraemic and 60.0% (18/30) non-viraemic (p = 0.56). NNRTI-ADRMs were significantly higher among viraemic ALHIV (69.2% vs. 46.7%, p = 0.030). Regarding immunity, those with CD4 nadir < 350 cells/µl had significantly higher rates of ADRMs [adjusted odds ratio (aOR) = 3.20 (1.36-95.53), p = 0.03]. In relation to COVID-19 immunity, overall SARS-CoV-2 IgG seropositivity was 28.3% (17/60), whereas 0% (0/60) were seropositive to IgM; in particular, those with CD4 count nadir ≥ 350 cells/µl had higher odds of SARS-CoV-2 IgG seropositivity [OR =7.85 (2.03-30.28), p < 0.01]. No significant association was found between SARS-CoV-2 IgG seropositivity and HIV-RNA (non-viraemic, 33.3%; viraemic, 16.7%; p = 0.18). SARS-CoV-2 RNA prevalence was 4.5% (2/44). The two positive participants were with low-levels of viral load (Ct > 30) and seropositive to IgG. CONCLUSION: In the context of virological success, the majority of ALHIV harbour ADRMs, essentially driven by NNRTI mutations and low CD4 nadir. During the current pandemic, about one-third of ALHIV were previously exposed to SARS-CoV-2. However, some children might have been exposed and uninfected and others might have been infected but showed no serological response at sampling. These findings support the use of NNRTI-sparing regimens and the implementation of COVID-19 barrier measures targeting ALHIV during such a pandemic.

HIV-1 residual risk and pre-treatment drug resistance among blood donors: A sentinel surveillance from Gabon.

BACKGROUND: Surveillance of HIV-1 pre-treatment drug resistance (PDR) is essential for ensuring the success of first-line antiretroviral therapy (ART). Beside population-based surveys, sentinel surveillance of PDR and circulating HIV-1 clades in specific populations such as blood donors could efficiently inform decision-making on ART program. We therefore sought to ascertain HIV-1 residual infection, the threshold of PDR and viral diversity among recently-diagnosed blood donors in Gabon. METHODS: A sentinel surveillance was conducted among 381 consenting blood donors at the National Blood Transfusion Center (NBTC) in Gabon from August 3,2020 to August, 31, 2021. In order to determine the residual risk of HIV transmission, viral load and HIV-1 Sanger-sequencing were performed at the Chantal BIYA International Reference Center (CIRCB)-Cameroon on HIV samples previously tested seronegative with ELISA in Gabon. Phylogeny was performed using MEGA X, PDR threshold>10% was considered high and data were analysed using p≤0.05 for statistical significance. RESULTS: Five HIV-negative blood donors had a detectable viral load indicating a high residual risk of HIV transmission. Among the samples successfully sequenced, four participants had major drug resistance mutations (DRMs), giving a threshold of PDR of 25% (4/16). By drug class, major DRMs targeting NNRTI (K103N, E138G), NRTIs (L210W) and PI/r (M46L). The most representative viral clades were CRF02_AG and subtype A1. The genetic diversity of HIV-1 had no significant effect on the residual risk in blood transfusion (CRF02_AG, P = 0.3 and Recombinants, P = 0.5). CONCLUSION: This sentinel surveillance indicates a high residual risk of HIV-1 transfusion in Gabon, thereby underscoring the need for optimal screening strategy for blood safety. Moreover, HIV-1 transmission goes with high-risk of PDR, suggesting suboptimal efficacy of ART. Nonetheless, the genetic diversity has limited (if any effect) on the residual risk of infection and PDR in blood donors.

Determinants of Immunovirological Response among Children and Adolescents Living with HIV-1 in the Central Region of Cameroon.

About 90% of new HIV-1 infections in children occur in sub-Saharan Africa, where treatment monitoring remains suboptimal. We sought to ascertain factors associated with immunovirological responses among an ART-experienced paediatric population in Cameroon. A laboratory-based and analytical study was conducted from January 2017 throughout December 2020 wherein plasma viral load (PVL) analyses and CD4 cell counts were performed. Viral suppression (VS) was defined as PVL < 1000 copies/mL and immunological failure (IF) as CD4 < 500 cells/µL for participants ≤5 years and CD4 < 250 cells/µL for those >5 years; p < 0.05 was considered statistically significant. Overall, 272 participants were enrolled (median age: 13 [9-15.5] years; 54% males); median ART duration 7 [3-10] years. Globally, VS was achieved in 54.41%. VS was 56.96% in urban versus 40.48% in rural areas (p = 0.04). IF was 22.43%, with 15.79% among participants ≤5 years and 22.92% among those >5 years (p = 0.66). IF was 20.43% in urban versus 33.33% in rural areas (p = 0.10). Following ART, IF was 25.82% on first-line (non-nucleoside reverse transcriptase inhibitors; NNRTI-based) versus 10.17% on second-line (protease inhibitor-based) regimens (p = 0.01). Interestingly, IF was 7.43% among virally suppressed versus 40.32% among virally unsuppressed participants (p < 0.0001). A low VS indicates major challenges in achieving AIDS' elimination in this paediatric population, especially in rural settings and poor immune statuses. Scaling up NNRTI-sparing regimens alongside close monitoring would ensure optimal therapeutic outcomes.

Evaluation of HIV-1 DNA levels among adolescents living with perinatally acquired HIV-1 in Yaounde, Cameroon: A contribution to paediatric HIV cure research in Sub-Saharan Africa.

Background: With the advent of antiretroviral therapy (ART), most children living with HIV in sub-Saharan Africa (SSA) are growing toward adolescence, with scarcity of evidence on the size of viral reservoirs to enhance paediatric cure research strategies. This study aims to compare HIV-1 proviral DNA levels according to virological response among adolescents living with perinatally acquired HIV-1 (ALPHIV) and identify associated-factors in the Cameroonian context. Methods: In this observational cohort study, HIV-1 RNA viremia and CD4+ T-cell count were assessed through RT-PCR and flow cytometry respectively at three time-points over 18 months of observation. At the third time-point, 80 randomly-selected participants were classified as with viremia (≥50 HIV-1 copies/mL; n = 40) or without viremia (<50 HIV-1 copies/mL; n = 40); immune-competent (≥500 CD4+ T cells/mm3) or immunocompromised (<500 CD4+ T cells/mm3). Among these participants, total HIV-1 DNA load was quantified through droplet digital PCR using Bio-Rad QX200. Results: Of the 80 randomly-selected adolescents, median [IQR] age was 15 (13-17) years, 56.2% were female, duration on ART was 9.3 [5.4-12.2] years. Among the 40 viremic ones (median viremia 7312 [283-71482]) HIV-1 copies/ml, 75.0% (30/40) were in virological failure (≥1000 HIV-1 copies/ml), while median of CD4 T cells were 494 [360-793] cell/mm3 with 48.8% (39/80) immunocompromised. No significant variation in HIV-1 RNA viremia and CD4 T cell count was observed between the three time-points, and 13.7% (11/80) adolescents remained aviremic and immune-competent throughout (stable adolescents). A positive and moderate correlation (r = 0.59; p < 0.001) was found between HIV-1 DNA levels and HIV- 1 RNA viremia. Regarding the CD4 T cell count, a negative and weak correlation (r = -0.28; p = 0.014) was found with HIV-1 DNA loads only among adolescents with viremia. Starting ART within the first year of life, ART for over 9 years and aviremia appear as predictors of low HIV-1 DNA loads. Conclusion: Among ALPHIV, high HIV-1 RNA indicates an elevated viral reservoir size, representing a drawback to cure research. Interestingly, early ART initiation and longer ARTduration lead to sustained viral control and limited HIV-1 reservoir size. As limited size of viral reservoir appears consistent with viral control and immune competence, adolescents with sustained viral control (about 14% of this target population) would be candidates for analytical ART interruptions toward establishing paediatric post-treatment controllers in SSA.

XBB.1, BQ1.1 and atypical BA.4.6/XBB.1 recombinants predominate current SARS-CoV-2 Wavelets with flu-like symptoms in Cameroon: A snapshot from genomic surveillance.

As of December 2022, Cameroon had observed a slight resurgence of COVID-19, raising concerns on genomic surveillance of related-SARS-CoV-2 variants under circulation. Following a laboratory-based survey, positive SARS-CoV-2 samples detected from December-2022 through March-2023 were processed for targeted sequencing at the Chantal BIYA International Reference Centre (CIRCB) in Yaoundé-Cameroon. From all positive cases detected, 13 were successfully sequenced (mean age 34 years, 70% female); the majority of the cases were unvaccinated (70%, 9/13) and symptomatic (92%, 12/13); all with flu-like symptoms (100%, 12/12). Following RT-PCR, the median cycle threshold was 22.23 [18-24] for the N gene; and 24.09 [20-26] for the ORF gene, underscoring high viral loads. Phylogenetic analysis of nucleotide sequences identified four major sub-variants in circulation, of which BA.5 (3/13), the recombinants BQ.1.1 (4/13), XBB.1 (4/13) and novel atypical variant of BA.4.6/XBB.1 (2/13). This snapshot surveillance indicates the introduction/emergence and circulation of new Omicron sub-variants, all accompanied by minor/mild symptoms. However, these new sub-variants and recombinants call for continuous genomic surveillance to prevent further resurgence of Covid-19 epidemiological wave.

Empowering adolescents living with perinatally-acquired HIV: tailored CD4+ count assessment for optimized care, the EDCTP READY-study.

Background: The elevated rate of AIDS-related mortality in Sub-Saharan Africa among adolescents living with HIV (ALHIV) is influenced by various factors, notably immunosuppression, within a framework of limited therapeutic alternatives. We aimed to enhance the management of pediatric HIV by assessing the immune response and associated factors in perinatally-infected ALHIV on antiretroviral therapy (ART) in Cameroon. Methods: A cohort study was conducted from 2018-2020 among 271 ART-experienced ALHIV in Cameroon. Sociodemographic data, immunological (CD4), and virological (plasma viral load, PVL) responses were measured at enrolment (T0), 6-months (T1), and 12-months (T2) using PIMA CD4 (Abbott/Pantech (Pty) Ltd) and Abbott Applied Biosystem platform (Real-Time PCR m2000RT) respectively. Immunological failure (IF) was defined as absolute CD4 < 250 cells/mm3, and Virological failure (VF) as PVL ≥ 1,000 copies/ml. A linear mixed-effects model with R version 4.4.1 was used to estimate both fixed and random effects, with significance set at p < 0.05. Results: Of the 271 perinatally-infected ALHIV enrolled over three phases, females were predominant (55.7, 55.1, and 56.0%); median age was 14 (IQR: 12-17); majority of the participants were followed-up in urban areas (77.5, 74.5, and 78.6%); and the age distribution favored older adolescents (48.7, 61.2, and 58.5%). Most participants achieved clinical success (93.1, 89.7, 88.9%), predominantly on first-line ART (80.8, 66.2, and 53.0%), with good adherence (64.2, 58.9, and 64.5%). Most participants had secondary education (67.2, 70.1, and 67.5%). Median CD4+ counts fluctuated overtime, with values of 563 (IQR: 249.0-845.0), 502 (IQR: 319.0-783.5), and 628 (IQR: 427.5-817.5), respectively. Of note, being male was linked to a reduction in CD4+ count compared to females, [-200.63 (-379.32 to -21.95), p = 0.028]. Similarly, late adolescence was associated with lower CD4+ counts compared to early adolescence, [-181.08 (-301.08 to -61.09), p = 0.003]. Moreover, participants experiencing VF showed significantly lower CD4+ counts compared to those with undetectable viral loads, [-353.08 (-465.81 to -240.36), p < 0.001]. Additionally, there was a marginally significant interaction between male gender and secondary educational level, [209.78 (-6.94-426.51), p = 0.058]. Conclusion: Among perinatally-infected ALHIV, age, gender, educational level, and virological status are key factors influencing their immune health and treatment outcomes. Prioritizing targeted interventions and close monitoring within these subgroups is crucial for optimal management, employing holistic care strategies that consider not only medical interventions but also psychosocial support and education.

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

Introduction: An 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. Methods: A 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. Results: The 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. Conclusion: Knowledge 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.

Characterisation of HIV-1 reservoirs in paediatric populations: protocol for a systematic review and meta-analysis.

INTRODUCTION: The success of antiretroviral therapy (ART) has changed HIV from a deadly to a chronic infection, thus increasing the transitioning from infancy toward adulthood. However, the virostatic nature of antiretrovirals maintains viruses in sanctuaries, with reactivation potentials. Because current ARTs are very limited for children, the emergence of new HIV epidemics driven by HIV drug-resistance mutations is favoured. Our systematic review aims to estimate the global burden of archived drug-resistance mutations (ADRMs) and the size of reservoir (HIV-1 DNA load), and their associated factors in children and adolescents. METHODS AND ANALYSIS: Papers from the PubMed/MEDLINE, Google Scholar, ScienceDirect, African Journals Online and Academic Medical Education Databases will be systematically identified using the keywords: "HIV-1 reservoirs", "viral reservoirs", "HIV-1 DNA", infants, adolescents, child and children, linked by the following Boolean operators: 'OR' and 'AND'. Randomised and non-randomised trials, cohort studies and cross-sectional studies published in French or English from January 2002 will be included, while case reports, letters, comments, reviews, systematic reviews and meta-analyses, and editorials will be excluded. All studies describing data on ADRMs, HIV-1 DNA load and/or immunological markers among children/adolescents will be eligible. A random-effects model will be used to calculate the pooled prevalence of ADRMs. Data will be reported according to type of viral reservoir (peripheral blood mononuclear cells, CD4 cells), geographical location (country/continent), ethnicity/race, age (infants vs adolescents), gender, HIV-1 clades, ART exposure (naïve vs treated, drug class, type of regimen, age at ART initiation and treatment duration), WHO clinical staging (I, II, III, IV), immune status (immune compromised vs immune competent) and virological response (viraemic vs non-viraemic). Multivariate logistic regression will be performed to determine predictors of HIV reservoir profile in paediatric populations. The primary outcome will be to assess the genotypical and quantitative profile of HIV reservoirs, while the secondary outcomes will be to identify factors associated with ADRMs and reservoir size in paediatric populations. ETHICS AND DISSEMINATION: Ethical approval is not applicable for this study as it will be based on published data. Results will be disseminated via a peer-reviewed scientific journal and relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42022327625.

HIV-1 genotypic profiling ensures effective response to third-line antiretroviral therapy in Cameroon.

In order to limit the emergence of human immunodeficiency virus (HIV) drug resistance in a context of limited antiretroviral options, we sought to evaluate the efficacy of third-line (3L) regimens considering HIV genotypic resistance profile at initiation of 3L in Cameroon. A cohort-study was conducted from January-September 2020 among patients initiating a 3L antiretroviral therapy regimen at the Yaoundé Central Hospital. HIV-1 protease-reverse transcriptase was sequenced at the Chantal Biya international reference center for research on HIV/AIDS prevention and management and results were interpreted using Stanford HIVdbv8.3. Good virological response (viral load < 390 copies/mL) was assessed after 12 months using OPP-ERA platform. Statistical analyses were performed using Epi Info v7.2.2.6, with P < .05 considered statistically significant. Of the 38 patients initiating 3L with an available genotyping (42% female; median age, 49 [39-57] years), median cluster of differentiation type 4 count and viral load were 173 [34-374] cells/µL and 169,322 [30,382-551,826] copies/mL, respectively. At enrollment, all patients harbored resistance to reverse transcriptase inhibitors and 66% (25/38) to protease-inhibitors, although 63% (24/38) were still susceptible to darunavir/ritonavir. Preferred 3L regimen was dolutegravir + darunavir/r + tenofovir + lamivudine (51%) and median duration on 3L was 21 [17-32] months. Interestingly, 82% (31/38) of the participants achieved good virological response on 3L, regardless of genotypic profile at recruitment, variations in 3L regimens (P = .9) and baseline cluster of differentiation type 4 count (P = .3). Despite the high burden of reverse transcriptase inhibitor - and protease inhibitor boosted by ritonavir drug resistance, genotyping-guided 3L regimens is accompanied by virological success in most patients. This high efficacy, most likely due to use of high genetic barrier antiretrovirals, requires continuous adherence support alongside close monitoring for long-term effectiveness in similar programmatic settings.

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.

BACKGROUND: The 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. OBJECTIVE: We sought to assess the pooled MTCT rate, its risk-factors, and to characterize viral reservoirs of infected-children in Cameroon. METHODS: All 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. RESULTS: We 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. CONCLUSION: In 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.

COVID-19 preventive social-behavioural practices and exposure to SARS-CoV-2 among residents in the city of Yaounde: Lessons from the early phase of the pandemic in Cameroon.

Non-pharmaceutical interventions remain key in mitigating the spread of SARS-CoV-2. We sought to assess COVID-19 preventive, social-behavioural practices, and SARS-CoV-2 exposure through IgG rapid tests. This was a cross-sectional survey among 971 respondents residing in 180 households within the "Cite Verte" health district of Yaounde-Cameroon, from October-November 2020. Using a structured questionnaire, data on SARS-CoV-2 preventive and social behavioural practices were collected, while exposure to SARS-CoV-2 was determined by IgG profiling. p<0.05 was considered statistically significant. Overall, 971 participants were enrolled, among whom 56.5% were females. The age group 15-29 (33.5%) and those with a secondary level of education (44.7%) were most represented. Regarding preventive/social behavioural practices, the least respected measure was "stopped work", 49.1%, while the most respected was "Respect of hygiene rules", 93.8%. Women obeyed preventive measures more than men, with 87.6% vs 81.0% adhering to the lockdown, (p = 0.005) and 95.5% vs 91.7% to hygiene rules (p = 0.017). The age range 45-64 years was the least adherent to the lockdown rule, with 75.2% (38/153), p<0.0001. Only 24.7% (73/295) and 6.1% (59/295) of the symptomatic individuals reported having sought medical consultation and Covid-19 testing respectively. In addition, up to 69.8% (555/795) felt healthcare facilities were high-risk sites for getting infected, p = 0.002. Exposure to SARS-CoV-2 by IgG positivity was 31.1% (302/971), with men recording a higher proportion of viral exposure, 51.0% (154/302), p = 0.021. After adjusting for gender, age, education, and occupation; salaried worker (p = 0.029; OR: 0.29), and trading (p = 0.001; OR: 0.23) least complied with lockdown rule. In this community of Cameroonian residents highly exposed to COVID-19, many perceived healthcare facilities as high-risk zones for SARS-CoV-2 infection and consequently did not seek medical interventions. Thus, in the context of such a pandemic, advocacy on risk communication and community engagement for health-seeking attitudes should preferentially target men and those afraid of pandemics.

Viral suppression in the era of transition to dolutegravir-based therapy in Cameroon: Children at high risk of virological failure due to the lowly transition in pediatrics.

This study aimed to compare viral suppression (VS) between children, adolescents, and adults in the frame of transition to dolutegravir (DTG)-based antiretroviral therapy (ART) in the Cameroonian context. A comparative cross-sectional study was conducted from January 2021 through May 2022 amongst ART-experienced patients received at the Chantal BIYA International Reference Centre in Yaounde-Cameroon, for viral load (VL) monitoring. VS was defined as VL < 1000 copies/mL and viral undetectability as VL < 50 copies/mL. Chi-square and multivariate binary logistic regression models were used to identify factors associated with VS. Data were analyzed using SPSS v.20.0 (SPSS Inc., Chicago, Illinois), with P < .05 considered significant. A total of 9034 patients (72.2% females) were enrolled. In all, there were 8585 (95.0%) adults, 227 (2.5%) adolescents, and 222 (2.5%) children; 1627 (18.0%) were on non-nucleoside reverse transcriptase-based, 290 (3.2%) on PI-based, and 7117 (78.8%) on DTG-based ART. Of those on DTG-based ART, only 82 (1.2%) were children, 138 (1.9%) adolescents, and 6897 (96.9%) adults. Median (interquartile range) duration on ART was 24 (12-72) months (24 months on Tenofovir + Lamivudine + Dolutegravir [TLD], 36 months on other first lines, and 84 months on protease inhibitors boosted with ritonavir-based regimens). Overall, VS was 89.8% (95% confidence interval: 89.2-90.5) and viral undetectability was 75.7% (95% confidence interval: 74.8-76.7). Based on ART regimen, VS on Non-nucleoside reverse transcriptase-based, protease inhibitors boosted with ritonavir-based, and DTG-based therapy was respectively 86.4%, 59.7%, and 91.8%, P < .0001. Based on ART duration, VS was respectively 51.7% (≤24 months) versus 48.3% (≥25 months), P < .0001. By gender, VS was 90.9% (5929) in females versus 87.0% (2183) in males, P < .0001; by age-range, VS moved from 64.8% (144) in children, 74.4% (169) adolescents, to 90.8% (7799) adults, P < .0001. Following multivariate analysis, VS was associated with adulthood, female gender, TLD regimens, and combination antiretroviral therapy duration > 24 months (P < .05). In Cameroon, ART response indicates encouraging rates of VS (about 9/10) and viral undetectability (about 3/4), driven essentially by access to TLD based regimens. However, ART response was very poor in children, underscoring the need for scaling-up pediatric DTG-based regimens.

Global burden of SARS-CoV-2 infection, hospitalization and case fatality rate among COVID-19 vaccinated individuals and its associated factors: A systematic review and meta-analysis protocol.

BACKGROUND: COVID-19 has been the most important public health concern worldwide since 2020. Several vaccines are now available to help in controlling COVID-19 associated morbidity and mortality. This study will aim to provide the global and regional prevalence of SARS-CoV-2 infection as well as an estimate of disease severity among COVID-19 vaccinated individuals. MATERIALS AND METHODS: In order to determine the global burden of SARS-CoV-2 infection among vaccinated individuals, we will systematically extract and review papers from PubMed/MEDLINE, Excerpta Medica database (EMBASE), Cochrane Central Register of Controlled Trials (CENTRAL), Science direct and Cumulative Index to Nursing and Allied Health Literature (CINAHL). All the studies describing the prevalence and/or disease severity (hospitalization and case fatality rate) data of COVID-19 among individuals who received a partial or complete dose of WHO-approved COVID-19 vaccines will be eligible. A random effect model will be used to calculate the pooled prevalence and to estimate the disease severity. Subgroup analysis will be performed to explore the association between the number of vaccine doses received and the COVID-19 burdens. DISCUSSION: This systematic review and meta-analysis will provide the global estimate data on pooled prevalence, hospitalization and case fatality rates of COVID-19 among vaccinated individuals. Moreover, the factors associated with reinfection and disease severity will be equally investigated in the meta-analysis. The results of this study will contribute in the understanding and estimation of the global burden of COVID-19 among vaccinated individuals. Findings will provide meaningful information for the success of the current global rollout of COVID-19 vaccination strategies and pave the way for future interventions. SYSTEMATIC REVIEW REGISTRATION: CRD42021273074.

HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: A systematic review and meta-analysis.

As sub-Saharan Africa (SSA) countries are transitioning to dolutegravir (DTG)-based ART, baseline data are required for optimal monitoring of therapeutic response. In this frame, we sought to generate up-to-date evidence on the use of integrase-strand transfer inhibitors (INSTI) and associated drug resistance mutations (DRMs) within SSA. In this systematic review and meta-analysis, we included randomized and non-randomized trials, cohort-studies, cross-sectional studies, and case-reports published on INSTI or integrase DRMs in SSA. We included studies of patients exposed to DTG, raltegravir (RAL) or elvitegravir (EVG). Primary outcomes were "the rate of virological control (VC:<50copies/ml)" and "the presence of DRMs" on INSTI-based regimens among patients in SSA. We synthesised extracted data using subgroup analysis, and random effect models were used where appropriate. Additional analyses were conducted to assess study heterogeneity. We identified 1,916 articles/citations through database searches, of which 26 were included in the analysis pertaining to 5,444 patients (mean age: 37±13 years), with 67.62% (3681/5444) female. Specifically, 46.15% (12/26) studies focused on DTG, 26.92% (7/26) on RAL, 23.08% (6/26) on both DTG and RAL, and 3.85% (1/26) on EVG. We found an increasing use of DTG overtime (0% before 2018 to 100% in 2021). Median treatment duration under INSTI-based regimens was 12 [9-36] months. Overall, the rate of VC was 88.51% [95%CI: 73.83-97.80] with DTG vs. 82.49% [95%CI: 55.76-99.45] and 96.55% [95%CI: 85.7-100.00] with RAL and EVG, respectively. In univariate analysis, VC with DTG-containing vs. other INSTI-regimens was significantly higher (OR = 1.44 [95%CI: 1.15-1.79], p = 0.0014). Among reported DRMs at failure, the only DTG resistance-mutations were G118R and R263K. In SSA, DTG presents a superiority effect in VC compared to other INSTIs. Nonetheless, the early detection of INSTI-DRMs calls for sentinel surveillance for a successful transition and a sustained efficacy of DTG in SSA. PROSPERO Registration Number: CRD42019122424.

High performance of integrase genotyping on diverse HIV-1 clades circulating in Cameroon: toward a successful transition to dolutegravir-based regimens in low and middle-income countries.

A successful transition to dolutegravir-based regimens in low and middle-income countries (LMICs) requires an integrase genotyping assay effective on diverse HIV-1 clades. We herein developed and validated an in-house integrase genotyping protocol on plasma samples from 195 HIV-infected patients in Cameroon. Median [IQR] viremia was 23,574 (518-109,235) copies/mL; 128/195 participants had ≥1000copies/mL (i.e., WHO-threshold for genotypic resistance testing in LMICs). A total of 18 viral clades were detected: 72(51.1%) CRF02_AG, 38(26.9%) pure subtypes and 31(22.0%) other recombinants. Following WHO-threshold (≥1000copies/ml), sequencing performance was 82.81%(106/128). Regarding viremia, performance was 85.00%(68/80) with ≥100,000copies/mL versus 76.67%(23/30) with 10,000 to 99,999copies/mL (P = 0.22); 83.33%(15/18) with 1,000 to 99,999copies/mL (P = 0.55); 73.68%(14/19) with 500 to 999copies/mL (P = 0.19); 50%(13/26) for 200 to 499copies/mL (P = 0.0005) and 36.36%(8/22) for <200copies/mL (P < 0.0001). The developed in-house integrase-genotyping is highly effective on both pure and recombinant viral clades, even at low-level viremia. This performance underscores its usefulness in monitoring integrase-resistance mutations and supporting the scale-up of dolutegravir-based regimens in LMICs.

Epidemiological, virological and clinical features of SARS-CoV-2 among individuals during the first wave in Cameroon: Baseline analysis for the EDCTP PERFECT-Study RIA2020EF-3000.

In Cameroon, COVID-19 infection spread rapidly and nationwide, with up to 721 deaths reported. To the best of our knowledge, no study reported the on-theground data using a large patients' dataset to give a comprehensive knowledge on COVID-19 pandemic in Cameroon. The objective of this study was to shade lights on the epidemiological, virological and clinical features of COVID-19 in the Cameroonian context. An observational study was conducted among symptomatic and asymptomatic individuals tested for SARS-CoV-2 by PCR on nasopharyngeal samples from April 22nd, 2020 to January 5th, 2021. Out of 14119 individuals (59.8% male), overall SARS-CoV-2 positivity was 12.7% (from 7.9% in <10 years to 17.3% in >60 years, p<0.001). The positivity rate of symptomatic individuals was 36.1% versus 9.8% among asymptomatic ones, p<0.001. Age group ≤10 [aOR (95%CI): 0.515 (0.338-0.784), p=0.002] and being symptomatic [aOR (95% CI): 5.108 (4.521-5.771), p<0.001] were predictors of SARS-CoV-2 positivity. Regarding PCR Cycle Threshold (CT), 53.8% of positive individuals had a CT <30. According to age, compared to older individuals, those aged 21-40 years showed a higher proportion with high viraemia (CT<20; 21.3% versus 12.5% respectively, p=0.003). Similarly, symptomatic individuals showed a higher proportion with high viraemia (22.4%), when compared to asymptomatic (13.9%); p<0.001. During this first wave of the pandemic, overall SARS-CoV-2 positivity remained high (>10%) and was associated with the presence of symptoms and older age. Most of the infection is among young and asymptomatic individuals, suggesting the "track-and-test" strategy should target these potential transmitters.

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.

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 Yaoundé 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 < 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 (>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.

High concordance in SARSCoV-2 detection between automated (Abbott m2000) and manual (DaAn gene) RT-PCR systems: The EDCTP PERFECT-Study in Cameroon.

Molecular diagnosis of COVID-19 is critical to the control of the pandemic, which is a major threat to global health. Several molecular tests have been validated by WHO, but would require operational evaluation in the field to ensure their interoperability in diagnosis. In order to ensure field interoperability in molecular assays for detection of SARS-CoV-2 RNA, we evaluated the diagnostic concordance of SARS-CoV-2 between an automated (Abbott) and a manual (DaAn gene) realtime PCR (rRT-PCR), two commonly used assays in Africa. A comparative study was conducted on 287 nasopharyngeal specimens at the Chantal BIYA International Reference Centre (CIRCB) in Yaounde- Cameroon. Samples were tested in parallel with Abbott and DaAn gene rRT-PCR, and performance characteristics were evaluated by Cohen's coefficient and Spearman's correlation. A total of 273 participants [median age (IQR) 36 (26-46) years] and 14 EQA specimens were included in the study. Positivity was on 30.0% (86/287) Abbott and 37.6% (108/287) DaAn gene. Overall agreement was 82.6% (237/287), with k=0.82 (95%CI: 0.777-0.863), indicating an excellent diagnostic agreement. The positive and negative agreement was 66.67% (72/108) and 92.18 % (165/179) respectively. Regarding Viral Load (VL), positive agreement was 100% for samples with high VLs (CT<20). Among positive SARS-CoV- 2 cases, the mean difference in Cycle Threshold (CT) for the manual and Cycle Number (CN) for the automated was 6.75±0.3. The excellent agreement (>80%) between the Abbott and DaAn gene rRTPCR platforms supports interoperability between the two assays. Discordance occurs at low-VL, thus underscoring these tools as efficient weapons in limiting SARS-CoV-2 community transmission.

HIV-1 Gag gene mutations, treatment response and drug resistance to protease inhibitors: A systematic review and meta-analysis protocol.

BACKGROUND: Some mutations in the HIV-1 Gag gene are known to confer resistance to ritonavir-boosted protease inhibitors (PI/r), but their clinical implications remain controversial. This review aims at summarizing current knowledge on HIV-1 Gag gene mutations that are selected under PI/r pressure and their distribution according to viral subtypes. MATERIALS AND METHODS: Randomized and non-randomized trials, cohort and cross-sectional studies evaluating HIV-1 Gag gene mutations and protease resistance associated mutations, will all be included. Searches will be conducted (from January 2000 onwards) in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Latin American and Caribbean Health Sciences Literature (LILAC), Web of Science, African Journals Online, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Hand searching of the reference lists of relevant reviews and trials will be conducted and we will also look for conference abstracts. Genotypic profiles of both Gag gene and the protease region as well as viral subtypes (especially B vs. non B) will all serve as comparators. Primary outcomes will be the "prevalence of Gag mutations" and the "prevalence of PI/r resistance associated mutations". Secondary outcomes will be the "rate of treatment failure" and the distribution of Gag mutations according to subtypes. Two reviewers will independently screen titles and abstracts, assess the full texts for eligibility, and extract data. If data permits, random effects models will be used where appropriate. This study will be reported according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta Analyses. DISCUSSION: This systematic review will help identify HIV-1 Gag gene mutations associated to PI/r-based regimen according to viral subtypes. Findings of this review will help to better understand the implications of the Gag gene mutations in PI/r treatment failure. This may later justify considerations of Gag-genotyping within HIV drug resistance interpretation algorithms in the clinical management of patients receiving PI/r regimens. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42019114851.