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.

Evaluation of HIV-1 capsid genetic variability and lenacapavir (GS-6207) drug resistance-associated mutations according to viral clades among drug-naive individuals.

OBJECTIVES: We evaluated the HIV-1 capsid genetic variability and lenacapavir drug resistance-associated mutations (DRMs) among drug-naive individuals across HIV-1 clades. METHODS: A total of 2031 HIV-1 sequences from drug-naive patients were analysed for capsid amino acid modification and the prevalence of lenacapavir DRMs. Amino acid positions with <5% variability were considered as conserved and variability was analysed by HIV-1 clades. RESULTS: Overall, 63% (148/232) of amino acid positions were conserved in the capsid protein. Of note, conservation was consistent in specific binding residues of cellular factors involved in viral replication [CypA (G89, P90), CPSF6 (Q4, N57, N74, A77, K182) and TRIM-NUP153 (R143)], while N183 (12.31%) was the only non-conserved lenacapavir binding residue. The overall prevalence (95% CI) of lenacapavir DRMs was 0.14% (0.05-0.44) (3/2031), with M66I (0.05%) and Q67H (0.05%) observed in subtype C, and T107N (0.05%) observed in CRF01_AE. Moreover, polymorphic mutations M66C (n = 85; 4.18%), Q67K (n = 78; 3.84%), K70R (n = 7; 0.34%), N74R (n = 57; 2.81%) and T107L (n = 82; 4.03%) were observed at lenacapavir resistance-associated positions. CONCLUSIONS: The low level of lenacapavir DRMs (<1%) supports its predicted effectiveness for treatment and prevention, regardless of HIV-1 clades. The established conserved regions hence serve as a hallmark for the surveillance of novel mutations potentially relevant for lenacapavir resistance.

Baseline integrase drug resistance mutations and conserved regions across HIV-1 clades in Cameroon: implications for transition to dolutegravir in resource-limited settings.

BACKGROUND: Transition to dolutegravir-based regimens in resource-limited settings (RLS) requires prior understanding of HIV-1 integrase variants and conserved regions. Therefore, we evaluated integrase drug resistance mutations (DRMs) and conserved regions amongst integrase strand transfer inhibitor (INSTI)-naive patients harbouring diverse HIV-1 clades in Cameroon. METHODS: A cross-sectional study was conducted amongst 918 INSTI-naive patients from Cameroon (89 ART-naive and 829 ART-experienced patients). HIV-1 sequences were interpreted regarding INSTI-DRMs using the Stanford HIVdb v8.9-1 and the 2019 IAS-USA list. Amino acid positions with <1% variability were considered as highly conserved. Subtyping was performed by phylogeny. RESULTS: Overall prevalence (95% CI) of INSTI-DRMs was 0.8% (0.4-1.7), with 0.0% (0.0-4.0) amongst ART-naive versus 0.9% (0.5-1.9) amongst ART-experienced patients; P = 0.44. Accessory mutations (95% CI) were found in 33.8% (30.9-37.0), with 38.2% (28.1-49.1) amongst ART-naive versus 33.4% (30.4-36.7) amongst ART-experienced patients; P = 0.21. Of 288 HIV-1 integrase amino acid positions, 58.3% were highly conserved across subtypes in the following major regions: V75-G82, E85-P90, H114-G118, K127-W132, E138-G149, Q168-L172, T174-V180, W235-A239 and L241-D253. Wide genetic diversity was found (37 clades), including groups M (92.3%), N (1.4%), O (6.2%) and P (0.1%). Amongst group M, CRF02_AG was predominant (47.4%), with a significantly higher frequency (95% CI) of accessory mutations compared with non-AG [41.4% (36.8-46.0) versus 27.1% (23.3-31.2) respectively; P < 0.001]. CONCLUSIONS: The low baseline of INSTI-DRMs (<1%) in Cameroon suggests effectiveness of dolutegravir-based regimens. In spite of high conservation across clades, the variability of accessory mutations between major circulating strains underscores the need for monitoring the selection of INSTI-DRMs while scaling up dolutegravir-based regimens in RLS.

Human immunodeficiency virus is a driven factor of human papilloma virus among women: evidence from a cross-sectional analysis in Yaoundé, Cameroon.

BACKGROUND: Human papillomavirus (HPV) is the leading cause of cervical cancers, causing 270.000 deaths annually worldwide of which 85% occur in developing countries with an increasing risk associated to HIV infection. This study aimed at comparing HPV's positivity and genotype distribution in women according to their HIV status and determinants. METHODS: A comparative study was carried out in 2012 at the Chantal BIYA International Reference Centre (CIRCB) among 278 women enrolled consecutively at the General Hospital and the Gynaeco-Obstetric and Paediatric Hospital of the City of Yaoundé. HPV genotyping was performed by real-time PCR, HIV serological screening by serial algorithm, CD4 T cell phenotyping by flow cytometry and HIV viral load by Abbott m2000RT. Statistical analyses were performed using Microsoft Excel 2016 and Graph Pad version 6.0 software; with P < 0.05 considered statistically significant. RESULTS: Globally, mean age was 37 ± 3 years; median CD4-count for HIV+ was 414 cells/mm3 [IQR: 264.75-588] and median viremia was 50 RNA copies/mL [IQR: < 40-8288]. Overall HPV rate was 38.49% (107/278); 58.88% for single women vs. others (28.97% married, 2.80% divorced, 9.34% for widows), OR: 2.164; p = 0.0319. Following HIV status, HPV rate was 43.48% (80/184) among HIV+ vs. 28.72% (27/94) among HIV- (OR: 1.937; p < 0.0142); HPV genotypes among HIV+ vs. HIV- were respectively distributed as follows: genotype 16 (3.75% vs. 0.00%, p = 0.57), genotype 18 (3.75% vs. 3.70%, p = 1.00), co-infection 16 and others (8.75% vs. 7.40%, p = 1.00), co-infection 18 and others (8.75% vs. 11.11%, p = 0.71), co-infection 16, 18 and others (2.50% vs. 0.00%, p = 1.00) and other genotypes (72.50% vs. 77.78%, p = 0.80). Among HIV+ participants, HPV rate following CD4 was 62.88% (61/97) for CD4 < 500 vs. 35.71% (20/56) for CD4 ≥ 500 (OR: 3.05; p = 0.0012) while HPV rate following HIV viremia was 42.71% (41/96) with < 1000 RNA copies/ml vs. 66.00% (33/50) with > 1000 RNA copies/ml (OR = 0.384; p = 0.009). CONCLUSION: In Yaoundé, HPV rate appear to be very high, with higher rates of genotypes other than 16 and 18. In the event of HIV infection, the risk of HPV positivity is two times higher, favoured essentially by immunodeficiency. Thus, HIV-infected women should be closely monitored to prevent the emergence of cervical cancer.

Determinants of periodontitis according to the immunological and virological profiles of HIV-infected patients in Yaoundé, Cameroon.

BACKGROUND: HIV infection is associated to different oral manifestations (including periodontal diseases), which have decreased with the advent of antiretroviral therapy (ART). Yet, the occurrence of periodontitis is still consistent among patients with HIV living in sub Saharan-Africa, with limited evidence on the driven factors and mitigating measures in these settings. We aimed at evaluating the occurrence of periodontitis and its associated immunological and virological factors in patients with HIV living in Yaoundé, Cameroon. METHODS: We included 165 (44 ART-naïve and 121 ART-experienced) patients > 18 years old attending the Yaoundé Central Hospital and the Chantal BIYA International Reference Centre, from January-April 2018. The periodontal status was assessed by measuring the clinical attachment loss, periodontal pocket depth, plaques index and gingival bleeding index. CD4+/CD8+ cells and viremia were measured using the fluorescence-activated cell sorting method (FACS Calibur) and the Abbott m2000 RT HIV-1 RNA kit respectively. A standard-questionnaire concerning participants' medical records and oral hygiene methods was filled. Data was analyzed and p < 0.05 considered statistically significant. RESULTS: There was a significantly high prevalence of periodontitis in the ART-naïve (53.2%) compared to the ART-experienced group (37.3%), with a twofold increased risk of the ART-naïve population presenting with periodontitis than the ART-experienced population (OR 2.06, p = 0.03). More importantly, ART-naïve, patients with CD4 < 200 cells presented with higher risk of having periodontitis compared to those with higher CD4-values, with a threefold difference (OR 3.21). Worth noting, males presented with a higher risk of having clinical attachment loss (OR 6.07). There was no significant association between the occurrence of periodontitis and the CD8 (p = 0.45) or viremia (p = 0.10). CONCLUSION: In the Cameroonian context, a considerable number of adults infected with HIV suffer from periodontitis regardless of their treatment profile. Nonetheless, ART-naïve patients have a higher risk, indicating the protective role of ART. Interestingly, severely immune-compromised patients and men are vulnerable to periodontitis, thereby highlighting the need for clinicians to refer patients for regular periodontal screening especially male patients and those with low CD4. Such measures could greatly improve the quality of life of the population living with HIV in Cameroon.

Viral suppression in adults, adolescents and children receiving antiretroviral therapy in Cameroon: adolescents at high risk of virological failure in the era of "test and treat".

BACKGROUND: After the launching of the « Test & Treat ¼ strategy and the wider accessibility to viral load (VL), evaluating virological success (VS) would help in meeting the UNAIDS targets by 2020 in Cameroon. SETTING AND METHODS: Cross-sectional study conducted in the Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management (CIRCB), Yaoundé, Cameroon; data generated between October 2016 and August 2017 amongst adults, adolescents and children at 12, 24, 36 and ≥ 48 months on ART. VS was defined as < 1000 copies/mL of blood plasma and controlled viremia as VL < 50 copies/mL. Data were analysed by SPSS; p < 0.05 considered as significant. RESULTS: 1946 patients (70% female) were enrolled (1800 adults, 105 adolescents, 41 children); 1841 were on NNRTI-based and 105 on PI-based therapy; with 346 patients at M12, 270 at M24, 205 at M36 and 1125 at ≥ M48. The median (IQR) duration on was 48 months (24-48). Overall, VS was 79.4% (95% CI 77.6-81.2) and 67.1% (95% CI 64.9-69.1) had controlled viral replication. On NNRTI-based, VS was 79.9% vs. 71.4% on PIs-based, p = 0.003. By ART duration, VS was 84.1% (M12), 85.9% (M24), 75.1% (M36) and 77.2% (≥ M48), p = 0.001. By age, VS was 75.6% (children), 53.3% (adolescents) and 81.1% (adults), p < 0.001. CONCLUSIONS: In this sub-population of patients receiving ART in Cameroon, about 80% might be experiencing VS, with declining performance at adolescence, with NNRTI-based regimens, and as from 36 months on ART. Thus, improving VS may require an adapted adherence support mechanism, especially for adolescents with long-term treatment in resource-limited settings.

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.

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.

Rates of Viral Non-Suppression and Acquired HIV-1 Drug Resistance Emergence among Children during the Sociopolitical Crisis in the Northwest Region of Cameroon: A Call for Improved Monitoring Strategies.

BACKGROUND: Virological failure (VF) among children remains concerning, with high risks of HIV drug resistance (HIVDR) emergence and increased disease progression. Therefore, monitoring of viral non-suppression and emerging HIVDR is crucial, especially in the frame of sociopolitical unrest. OBJECTIVE: The study sought to determine the prevalence of VF and evaluate the acquired HIVDR and viral genetic diversity among children in the northwest region of Cameroon during the ongoing sociopolitical crisis. METHODS: A cross-sectional facility-based study was conducted among HIV-infected children aged ≤18 years, receiving antiretroviral therapy (ART) in urban and rural settings of Northwest Cameroon, from November 2017 through May 2018. Viral load (VL) was done using the Abbott m2000RealTime. Unsuppressed VL was defined as viral load ≥1,000 copies/ml. HIVDR testing was performed by sequencing of HIV-1 protease-reverse transcriptase at the Chantal Biya International Reference Center (CIRCB) using an in-house protocol. Drug resistance mutations (DRM) were interpreted using Stanford HIVdbv8.5 and phylogeny using MEGAv.6. Data were compared between urban and rural areas with p<0.05 considered statistically significant. RESULTS: A total of 363 children were recruited, average age of 12 years (urban) and 8 years (rural). VL coverage was 100% in the urban setting and 77% in the rural setting. Overall, VF was 40.5% (39% [130/332] in the urban setting and 41% (13/31) in the rural setting; p=0.45). Overall, viral undetectability (defined as VL<40 copies/ml) was 45.5% (46% (urban) and 45% (rural); p=0.47). Among those experiencing confirmed virological failure and who were successfully sequenced (n=35), the overall rate of HIVDR was 100% (35/35). By drug class, HIVDR rates were 97.1% (34/35) for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 97.1% (34/35) for NRTIs and 17.1% (6/35) for protease inhibitors (22.7% (5/22) in the urban setting and 7.7% [1/13] in the rural setting). CRF02_AG was the most prevalent viral clade (75%), followed by other recombinants (09_cpx, 11_cpx, 13_cpx, 22_01A1, 37_cpx) and pure subtypes (A1, F2, G, H). CONCLUSION: In this population of children and adolescents living with HIV in a context of socio-political instability in the North-West region of Cameroon, rates of viral non-suppression are high, and accompanied by HIVDR selection. Our suggests the need for a more differentiated care of these CAHIV, especially those in these regions faced with significant socio-economic and health impacts due to the ongoing crisis.

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.

SARS-CoV-2 genomic surveillance and reliability of PCR single point mutation assay (SNPsig® SARS-CoV-2 EscapePLEX CE) for the rapid detection of variants of concern in Cameroon.

Background: Surveillance of SARS-CoV-2 variants of concern (VOCs) and lineages is crucial for decision-making. Our objective was to study the SARS-CoV-2 clade dynamics across epidemiological waves and evaluate the reliability of SNPsig® SARS-CoV-2 EscapePLEX CE in detecting VOCs in Cameroon. Material and methods: A laboratory-based study was conducted on SARS-CoV-2 positive nasopharyngeal specimens cycle threshold (Ct)≤30 at the Chantal BIYA International Reference Centre in Yaoundé-Cameroon, between April-2020 to August-2022. Samples were analyzed in parallel with Sanger sequencing and (SNPsig® SARS-CoV-2 EscapePLEX CE), and performance characteristics were evaluated by Cohen's coefficient and McNemar test. Results: Of the 130 sequences generated, SARS-CoV-2 clades during wave-1 (April-November 2020) showed 97 % (30/31) wild-type lineages and 3 % (1/31) Gamma-variant; wave-2 (December-2020 to May-2021), 25 % (4/16) Alpha-variant, 25 % (4/16) Beta-variant, 44 % (7/16) wild-type and 6 % (1/16) mu; wave-3 (June-October 2021), 94 % (27/29) Delta-variant, 3 % (1/29) Alpha-variant, 3 % (1/29) wild-type; wave-4 (November-2021 to August-2022), 98 % (53/54) Omicron-variant and 2 % (1/54) Delta-variant. Omicron sub-variants were BA.1 (47 %), BA.5 (34 %), BA.2 (13 %) and BA.4 (6 %). Globally, the two genotyping methods accurately identified the SARS-CoV-2 VOCs (P = 0.17, McNemar test; Ka = 0.67). Conclusion: Genomic surveillance reveals a rapid dynamic in SARS-CoV-2 strains between epidemiological waves in Cameroon. For wide-spread variant surveillance in resource-limited settings, SNPsig® SARS-CoV-2 EscapePLEX CEkit represents a suitable tool, pending upgrading for distinguishing Omicron sub-lineages.

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.

Evaluation of Viral Suppression in Paediatric Populations: Implications for the Transition to Dolutegravir-Based Regimens in Cameroon: The CIPHER-ADOLA Study.

Mortality in children accounts for 15% of all AIDS-related deaths globally, with a higher burden among Cameroonian children (25%), likely driven by poor virological response. We sought to evaluate viral suppression (VS) and its determinants in a nationally representative paediatric and young adult population receiving antiretroviral therapy (ART). A cross-sectional and multicentric study was conducted among Cameroonian children (<10 years), adolescents (10-19 years) and young adults (20-24 years). Data were collected from the databases of nine reference laboratories from December 2023 to March 2024. A conditional backward stepwise regression model was built to assess the predictors of VS, defined as a viral load (VL) <1000 HIV-RNA copies/mL. Overall, 7558 individuals (females: 73.2%) were analysed. Regarding the ART regimen, 17% of children, 80% of adolescents and 83% of young adults transitioned to dolutegravir (DTG)-based regimens. Overall VS was 82.3%, with 67.3% (<10 years), 80.5% (10-19 years) and 86.5% (20-24 years), and p < 0.001. VS was 85.1% on a DTG-based regimen versus 80.0% on efavirenz/nevirapine and 65.6% on lopinavir/ritonavir or atazanavir/ritonavir. VS was higher in females versus males (85.8% versus 78.2%, p < 0.001). The VS rate remained stable around 85% at 12 and 24 months but dropped to about 80% at 36 months after ART initiation, p < 0.009. Independent predictors of non-VS were younger age, longer ART duration (>36 months), backbone drug (non-TDF/3TC) and anchor drug (non-DTG based). In this Cameroonian paediatric population with varying levels of transition to DTG, overall VS remains below the 95% targets. Predictors of non-VS are younger age, non-TDF/3TC- and non-DTG-based regimens. Thus, efforts toward eliminating paediatric AIDS should prioritise the transition to a DTG-based regimen in this new ART era.

Variability of High-Risk Human Papillomavirus and Associated Factors among Women in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

BACKGROUND: Sub-Saharan Africa (SSA) carries the highest burden of high-risk human papillomavirus (HR-HPV) in the world, driven by, and together with, HIV infection. This systematic review aimed to identify HR-HPV genotypes and their associated factors among women in SSA. METHODS: A systematic review and meta-analysis of studies conducted in SSA on HR-HPV was conducted. Standard electronic databases were searched. R software version 3.6.0 was used for meta-analysis, with p < 0.05 considered statistically significant. RESULTS: We included 28 articles with a total of 22,652 participants. The overall pooled prevalence of HR-HPV genotypes was 55.13%, albeit high heterogeneity between studies. The overall pooled prevalence of HR-HPV genotypes in HIV-positive individuals was 75.51%, compared to 52.97% in HIV-negatives (OR = 4.68 (0.71-30.76)). HPV 16 (18%), 35 (10.12%), 52 (9.98%), 18 (9.7%) and 45 (6.82%) genotypes were the most prevalent. Twelve studies identified the most frequently reported risk factors associated with HR-HPV, with HIV infection (66.66%), multiple sexual partners (41.66%) and young age (41.66%) being the most reported risk factors. CONCLUSIONS: The combined prevalence of HR-HPV genotypes among women in general and HIV-infected women in particular remains high in SSA. The presence of several genotypes not covered by the vaccine is remarkable and suggests the need for revision of current vaccination policies to prevent HR-HPV infections.

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.

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

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. We sought to evaluate the effect of HIV-1 mutational profiling on immuno-virological response and ADR among APHI. 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 #x003C;250 cells/mm3), VF (viremia ≥1,000 copies/ml), and ADR were analyzed, with P#x003C;0.05 considered significant. 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#x003C;0.0001). From T1-T3 respectively, there were declining rates of IF (25.5, 18.9, and 9.83%, P#x003C;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. 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.