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.

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.

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.

HIV-1 subtype diversity and immuno-virological outcomes among adolescents failing antiretroviral therapy in Cameroon: A cohort study.

OBJECTIVE: We sought to evaluate the variability of HIV-1 and its effect on immuno-virological response among adolescents living with perinatally acquired HIV (APHI). METHODS: A cohort study was conducted from 2018-2020 among 311 APHI receiving antiretroviral therapy (ART) in Cameroon. Sequencing of protease and reverse transcriptase regions was performed for participants experiencing virological failure, VF, (Plasma viral load, PVL ≥ 1000 RNA copies/ml). HIV-1 subtypes were inferred by phylogeny; immuno-virological responses were monitored at 3-time points (T1-T3). Cox regression modeling was used to estimate adjusted hazard ratios (aHRs) of progression to: CD4 < 250, and PVL > 5log10, adjusted for acquired drug resistance, gender, ART line, adherence, and duration on treatment; p < 0.05 was considered statistically significant. RESULTS: Of the 141 participants in VF enrolled, the male-female ratio was 1:1; mean age was 15 (±3) years; and median [IQR] duration on ART was 51 [46-60] months. In all phases, 17 viral clades were found with a predominant CRF02_AG (58.2%, 59.4%, and 58.3%). From T1-T3 respectively, there was an increasing CD4 count (213 [154-313], 366 [309-469], and 438 [364-569] cells/mm3) and decline log10 PVL (5.23, 4.43, and 4.43), similar across subtypes. Among participants with CRF02_AG infection, duration of treatment was significantly associated with both rates of progression to CD4 < 250, and PVL > 5log10, aHR = 0.02 (0.001-0.52), and aHR = 0.05 (0.01-0.47) respectively. Moreover, four potential new HIV-1 recombinants were identified (CRF02_AG/02D, CRF02_AG/02A1F2, D/CRF02_AG, and AF2/CRF02_AG), indicating a wide viral diversity. CONCLUSION: Among APHI in settings like Cameroon, there is a wide genetic diversity of HIV-1, driven by CRF02_AG and with potential novel clades due to ongoing recombination events. Duration of treatment significantly reduces the risk of disease progression.