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

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

Maternal Socio-Demographic Factors and Mother-to-Child Transmission of HIV in the North Region of Cameroon.

Background and Objective: Socio-demographic factors are important risk factors for HIV infection. Maternal socio-demographic factors associated with HIV transmission from mother to child are not well elucidated to our knowledge. This study aimed to assess the maternal socio-demographic factors associated with HIV vertical transmission. Methods: A matched case-control study was conducted among children under 15 years of age born to HIV-infected mothers; using a structured questionnaire. The study was conducted in four health facilities in the North Region of Cameroon from July 2015 to October 2016. HIV- infected children were the cases, and HIV-uninfected children were the controls. One case was matched to nearly 4 controls according to age and sex. A total of 113 HIV-infected mothers of children under 15 years of age were purposively enrolled in the study. A questionnaire was administered to mothers and socio-demographic characteristics were collected. Blood samples were collected from the mother and her child for the determination or confirmation of HIV status. Univariate and multiple logistic regressions were used to assess associations between socio-demographic variables and HIV transmission from mother to child. Results: A total of 113 HIV-infected mothers and 113 children under 15 years of age were enrolled in this study. The majority of the mothers were between the age ranges of 25 years to 34 years. Of the 113 HIV-infected mothers, 69 (61%) were Muslims, 33 (32.1%) were not educated, 88 (77.8%) were unemployed, 80 (70.9%) were married, out of which 49 (61.6%) were engaged in a monogamous union. Of the 113 children (49.6%) were female, 25 (22.1%) were HIV-infected and 88 (77.9%) were HIV-exposed uninfected. At the univariate level, mothers who achieved a primary level of education were less likely to transmit HIV to infants compared to uneducated mothers [OR=0.28; CI (0.08-0.95); p=0.04]; and widows had a higher likelihood of HIV transmission to infants compared to married mothers [OR=4.65; CI (1.26-17.20); p=0.02]. Using multiple logistic regression, the maternal primary education level [aOR=0.32; CI (0.08-0.90); p=0.03] and widowerhood [aOR=7.05; CI (1.49-33.24); p=0.01] remained highly associated with the likelihood of HIV transmission to infants. Conclusion and Global Health Implications: Uneducated mothers and widows had a higher likelihood of mother-to-child transmission of HIV. Our findings should prompt reinforcement of prevention strategies targeting uneducated women and widows.

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

BACKGROUND: Antiretroviral therapy (ART) can bring HIV-1 levels in blood plasma to the undetectable level and allow a near-normal life expectancy for HIV-infected individuals. Unfortunately, ART is not curative and must be taken for life, because within a few weeks of treatment cessation, HIV viremia rebounds in most patients except for rare elite or posttreatment controllers of viremia. The primary source of this rebound is the highly stable reservoir of latent yet replication-competent HIV-1 proviruses integrated into the genomic DNA of the resting memory cluster of differentiation 4 (CD4+) T cells. To achieve a cure for HIV, understanding the cell reservoir environment is of paramount importance. The size and nature of the viral reservoir might vary according to the timing of therapy, therapeutic response, ART duration, and immune response. The mechanisms of reservoir maintenance generally depend on the levels/type of immune recognition; in addition, the dynamics of viral persistence are different between pediatric and adult populations. This difference could become more evident as children grow toward adolescence. OBJECTIVE: We aim to characterize the HIV reservoirs and their variability as per the virological and immunological profiles of HIV-1 non-B vertically infected adolescents receiving ART in Cameroon during the Adolescents' Viral Reservoirs study to provide accurate and reliable data for HIV cure research. METHODS: This study will involve HIV-1 non-B vertically infected adolescents selected from an existing cohort in our institution. Blood samples will be collected for analyzing immunological/virological profiles, including CD4/CD8 count, plasma viral load, immune activation/inflammatory markers, genotyping, and quantification of HIV-1 viral reservoirs. We will equally recruit an age-matched group of HIV-negative adolescents as control for immunological profiling. RESULTS: This study received funding in November 2021 and was approved by the national institutional review board in December 2021. Sample collection will start in November 2022, and the study will last for 18 months. The HIV-1 sequences generated will provide information on the circulating HIV-1 subtypes to guide the selection of the most appropriate ART for the participants. The levels of immune biomarkers will help determine the immune profile and help identify factors driving persistent immune activation/inflammation in HIV-infected adolescents compared to those in HIV-uninfected adolescents. Analysis of the virological and immunological parameters in addition to the HIV-1 reservoir size will shed light on the characteristics of the viral reservoir in adolescents with HIV-1 non-B infection. CONCLUSIONS: Our findings will help in advancing the knowledge on HIV reservoirs, in terms of size and genetic variability in adolescents living with HIV. Such evidence will also help in understanding the effects of ART timing and duration on the size of the reservoirs among adolescents living with HIV-a unique population from whom the findings generated will largely contribute to designing functional cure strategies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/41473.

Enhanced passive surveillance dengue infection among febrile children: Prevalence, co-infections and associated factors in Cameroon.

Dengue virus (DENV) causes a spectrum of diseases ranging from asymptomatic, mild febrile to a life-threatening illness: dengue hemorrhagic fever. The main clinical symptom of dengue is fever, similar to that of malaria. The prevalence of dengue virus infection, alone or in association with other endemic infectious diseases in children in Cameroon is unknown. The aim of this study was to determine the prevalence of dengue, malaria and HIV in children presenting with fever and associated risk factors. Dengue overall prevalence was 20.2%, Malaria cases were 52.7% and HIV cases represented 12.6%. The prevalence of dengue-HIV co-infection was 6.0% and that of Malaria-dengue co-infection was 19.5%. Triple infection prevalence was 4.3%. Dengue virus infection is present in children and HIV-Dengue or Dengue- Malaria co-infections are common. Dengue peak prevalence was between August and October. Sex and age were not associated with dengue and dengue co-infections. However, malaria as well as HIV were significantly associated with dengue (P = 0.001 and 0.028 respectively). The diagnosis of dengue and Malaria should be carried out routinely for better management of fever.

Protective Effect of the Combination of Wild-Type Genotypes (G/G and G/G) of CCR2-64V and SDF1-3A' Genes in Serodiscordant Couples in Yaounde-Cameroon.

BACKGROUND: There is growing evidence that polymorphisms in chemokine and chemokine receptor genes influence susceptibility to HIV infection and disease progression. However, not much is documented about the influence of these polymorphisms in HIV serodiscordant couples in Cameroon. OBJECTIVE: The objective of this study therefore was to determine the prevalence and the effect of the polymorphisms of CCR5-Δ32, CCR5 promoter 59029 A/G, CCR2-64I and SDF1-3'A gene in HIV serodiscordant couples in comparison to HIV negative seroconcordant and HIV positive seroconcordant couples in Yaoundé-Cameroon. METHODS: A total of 96 couples were recruited from five hospitals, of which 60 couples were HIV serodiscordant (test group), 18 HIV negative seroconcordant and 18 HIV positive seroconcordant couples were used as controls. Their genotypes for CCR5-Δ32, CCR5 promoter, CCR2 and SDF1 were analyzed using polymerase chain reaction (PCR) and restriction fragment length polymorphism. RESULTS: The allelic frequencies of these genes in the studied population were: 0%, 26.30%, 15.30% and 1.62% respectively for CCR5-Δ32, CCR5 promoter, CCR2 and SDF1. The frequency of the combination of CCR5 promoter and SDF1- (A/A+ G/G) wild-type genotype was higher in HIV-infected partners (82.92%) compared to uninfected partners (56.1%) in HIV serodiscordant couples (p= 0.0001). The combination of wild-type CCR2 and SDF1 genotypes (G/G + G/G) was higher among uninfected partners (80.48%) in HIV serodiscordant couples compared to the infected partners (60.97) (p= 0.005). CONCLUSION: HIV negative partner protection against HIV/AIDS infection may be attributed to the combination of wild-type genotypes (G/G and G/G) of CCR2 and SDF1 genes in HIV serodiscordant couples.

Tuberculosis diagnosis: algorithm that May discriminate latent from active tuberculosis.

Diagnosis of tuberculosis still faces a lot of challenges and is one of the priorities in the field of tuberculosis management. Deciphering the complex tuberculosis pathogenicity network could provide biomarkers for diagnosis. We discussed the distribution of HLA-B17, -DQB and -DRB together with QuantiFERON test results in tuberculosis infection. A case control study was done during which a total of 337 subjects were enrolled comprising 227 active tuberculosis (ATB), 46 latent tuberculosis infection (LTBI) and 64 healthy controls (HC). Sequence-specific primer polymerase chain reaction and immune epitope database were used to genotype samples and determine the epitope binding ability of the over-represented alleles respectively. QuantiFERON test was done according to manufacturer's instructions. The peptides HLA-B*5801 and HLA-DRB1*12 and the peptides HLA-B*5802 and HLA-DQB1*03 were found to be associated with latent tuberculosis while the haplotypes DRB1*10-DQB1*02 and DRB1*13-DQB1*06 were found to be associated with active tuberculosis (All p-values≤0.05). The association of HLA-B*5801 and HLA-B*5802 with latent tuberculosis was linked to their ability to bind or not mycobacterial antigens. DRB1*10-DQB1*02 haplotype was found to be over-represented in LTBI compared to ATB (p-value = 0.0015) while DRB1*13-DQB1*06 was found to be under-represented in LTBI compared to ATB (p-value = 0.0335). The DRB1*10-DQB1*02 haplotype was only found in the LTBI when compared with the ATB group. The present study suggests the following algorithm to discriminate LTBI from ATB: QuantiFERON+ and DRB1*10-DQB1*02 haplotype + may indicate LTBI; QuantiFERON+ and DRB1*10-DQB1*02 haplotype - may indicate ATB.

Maternal age, infant age, feeding options, single/multiple pregnancy, type of twin sets and mother-to-child transmission of HIV.

BACKGROUND: Some risk factors for mother-to-child transmission (MTCT) of HIV have been identified. To further reduce MTCT, other risk factors were evaluated. MATERIALS AND METHODS: A retrospective study on early infant diagnosis was conducted. Two-sided chi-square test was used to assess associations with infant HIV status. RESULTS: A total of 15 233 HIV-infected mothers and 15 404 infants were recruited. MTCT rate was 9.34%. Only 3.8% of infants born to mothers on antiretroviral treatment were infected. Under nevirapine, 4.1% of infants were infected. MTCT increased with infant' age at testing. Younger mothers tend to transmit more HIV (P = 0.003). More children were infected in single pregnancies compared with multiple pregnancies, P < 0.001. There were more infections in male-female twins' sets (P = 0.037). CONCLUSIONS: Maternal age, type of pregnancy and twins' sets are new MTCT risk factors. Strategies to further decrease transmission through family planning, pre/post natal consultations and clinical practices are needed.

HIV-1 Early Infant Diagnosis is an Effective Indicator of the Prevention of Mother-to-Child Transmission Program Performance: Experience from Cameroon.

BACKGROUND: Despite improvement in HIV prevention of mother-to-child transmission (PMTCT), there are still over 1,500 African infants newly infected daily. PMTCT elimination requires antiretroviral therapy (ART) throughout pregnancy and breastfeeding periods, while early infant diagnosis (EID) of HIV implies early treatment for those infected. Our study aimed at assessing the utility of EID program data in evaluating the implementation of PMTCT program in Cameroon, and in identifying the efficacy of existing PMTCT interventions and breastfeeding options on the events of HIV vertical transmission. METHODS: A study was conducted from 2010-2011 using PMTCT data from EID sites of six regions of Cameroon. PMTCT ARV regimens, breastfeeding options, and the child's HIV DNA-polymerase chain reaction (PCR) results were recorded. Statistical analyses were performed using Mann Whitney U and Fisher exact tests, with p<0.05 considered significant. RESULTS: A total of 2,505 mother-child pairs received ART, resulting is 4.3% (93) vertical transmission, against 31.3% (284/906) among mother-child pairs without exposure to any PMTCT intervention; p<0.00001. A statistically significant difference (p<0.00001) was also found between formula feeding (FF) (5.9%) versus exclusive breastfeeding (EBF) (12.5%), as well as between EBF versus mixed feeding (MF) (30%). With FF, when both mother-child pairs received PMTCT, only 2.9% (47/1603) vertical transmission was recorded versus 19.9% (48/241) for mother-child pairs without intervention; p<0.00001. Transmission rates were similar across infant age range [2.7% (10/376) for age ≤6 weeks, versus 2.5% (43/1807) for age >6 weeks-6 months]. Interestingly, babies aged 6 weeks receiving FF showed a significantly lower transmission rate (3.2%, 9/277) as compared to their counterparts with EBF (7.7%, 12/156); p<0.00001. CONCLUSION: Using EID dataset, it appears that considerable reduction in HIV MTCT may be achievable through access to ARV (option B+) and adequate infant feeding option (especially FF) in Cameroon. EID programme is therefore an effective routine approach for PMTCT programme evaluation in resource-limited settings.