Maternal and infant age, feeding options, ART use and singlet/multiple pregnancy affect rates of mother-to-child transmission of HIV in Cameroon, 2004–2013

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IMPLICATION OF FIVE AIDS RELATED GENES IN MOTHER-TO-CHILD TRANSMISSION AND ACQUISITION OF HUMAN IMMUNODEFICIENCY VIRUS 1 IN CAMEROON

Background: Genetic variants in the mother and/or infant have been described with evidence to be associated with mother-to-child transmission of HIV, but somehow with contradictory results depending on ethnic or geographic populations. We aimed at looking at the association between the allelic frequency of some genes with vertical transmission or acquisition of HIV in Cameroon. Methodology: A total of 262 mothers (212 HIV-infected and 50 HIV non-infected) with their babies (270 in total, 42 HIV exposed-infected, 178 HIV exposed non-infected and 50 HIV non-exposed) were recruited in Yaounde- Cameroon. Their genotypes for CCR5-Delta32, CCR5 promoter59029A/G, CCR2-64I, SDF1-3’A andTRIM5α-136Q were analyzed using polymerase chain reaction and restriction fragment length polymorphisms. Results: Allelic frequencies were 14.7%, 41.9%, 9.5% and 14.7% for CCR2-64I, CCR5-59029-A/G, TRIM5α-136Q, SDF1-3’A respectively in the mothers and 18.8%, 35.9%, 11.3% and 20.5% in the babies. No delta 32 mutation in the CCR5 gene was found. The mutant genotype was most significantly frequent in the non-transmitter than in the transmitter (p= 0.005) for the SDF-1 3'A. SDF1-3’A [Odd ratio = 1.69; 95% confidence interval: 0.1158 to 0.7277); was associated to MTCT, P = 0.008.The homozygote mutants for the CCR5-59029-G were significantly higher in the infected than in the exposed uninfected babies (p=0.04). The mutations in the other genes were neither implicated in the acquisition nor in the transmission. Conclusion: SDF1-3’A was associated to the reduction of MTCT. The CCR5-59029-A/G favored acquisition of HIV by babies. Our study showed that polymorphisms in chemokine ligand may be involved in MTCT

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.   Copyright © 2022 Nkenfou et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0

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

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

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

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

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

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

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