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.

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.

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.

HIV-1 Drug Susceptibility to Potential Second- and Third-Line Antiretroviral Regimens among Cameroonian Patients: Evidence from a Cross-sectional Design.

BACKGROUND: Scale-up of antiretroviral therapy (ART) and the growing number of long-term treated patients may favor multi-HIV drug resistance (HIVDR) in resource-limited settings. Understanding the burden of HIVDR with ART-exposure may provide new insights for an effective long-term management of infected patients. METHODS: Sixty-six HIV-infected individuals (18 ART-naïve, 24 failing first-line, 24 failing second-line ART) living in Yaoundé-Cameroon were evaluated by sequencing protease-reverse transcriptase (PR-RT, n=62), envelope-V3 loop (V3, n=58) and integrase (IN, n=30) regions. Drug resistance mutations (DRMs) were interpreted using Stanford University HIV drug resistance database and geno2pheno, while viral tropism prediction was done using geno2pheno, position-specific scoring matrices (PSSM) and Net charge rule. RESULTS: Participants, from naïve, first- to second-line, had respectively 5.30, 4.85 and 4.66 log HIV RNA, and 532, 203 and 146 CD4 cells/mm3), and infected with diverse HIV-1 non-B clades (58.1% CRF02_AG). Among ART-naïve patients, 6.7% harbored K103N, 28.6% had IN accessory-mutations (L74I, E157Q) and 26.7% carried CXCR4-tropic viruses. At first-line failure, 79.2% harbored DRMs to nucleoside and non-nucleoside RT inhibitors, 33.3% had IN accessory-mutations (L68I, L74I, T97A, E157Q), and 47.4% carried CXCR4-tropic viruses. At second-line failure, 91.3% harbored multi-DRMs to PR-RT inhibitors (with 52.2% and 4.3% DRMs to second-generation NNRTIs and darunavir/r, respectively), 27.3% had IN accessory-mutations (L74I, T97A, E157EQ), and 37.5% carried CXCR4-tropic viruses. CONCLUSION: Levels of PR-RT resistance increases with ART-exposure, with needs for new ART-options following second-line failure. IN inhibitors and darunavir/r are potentially suitable for a third-line regimen, while the use of maraviroc, etravirine or rilpivirine, requires individual genotypic testing.

Viral etiology of severe acute respiratory infections in hospitalized children in Cameroon, 2011-2013.

BACKGROUND: Severe acute respiratory illness (SARI) is recognized as an important cause of morbidity, mortality, and hospitalization among children in developing countries. Little is known, however, in tropical countries like Cameroon about the cause and seasonality of respiratory infections, especially in hospitalized settings. OBJECTIVES: Our study investigates the viral etiology and seasonality of SARI in hospitalized children in Yaounde, Cameroon. METHODS: Prospective clinic surveillance was conducted to identify hospitalized children aged ≤15 years presenting with respiratory symptoms ≤5-day duration. Demographic and clinical data, and respiratory specimens were collected. Nasopharyngeal samples were tested for 17 respiratory viruses using a multiplex polymerase chain reaction. The viral distribution and demographic data were statistically analyzed. RESULTS: From September 2011 through September 2013, 347 children aged ≤15 years were enrolled. At least one virus was identified in each of 65·4% children, of which 29·5% were coinfections; 27·3% were positive for human adenovirus (hAdV), 13·2% for human respiratory syncytial virus (hRSV), 11·5% for rhinovirus/enterovirus (RV/EV), 10·6% for human bocavirus (hBoV), 9·8% for influenza virus (Inf), 6·6% for human parainfluenza virus (hPIV), 5·7% for human coronavirus (hCoV), and 2·3% for human metapneumovirus (hMPV). While hRSV showed seasonal patterns, hAdV and RV/EV were detected throughout the year and no evident temporal patterns were observed for the remaining viruses. CONCLUSION: Respiratory viruses were associated with a high burden of hospitalizations among children in Cameroon. Nevertheless, additional studies evaluating asymptomatic Cameroonian children will be important in understanding the relationship between viral carriage and disease.

Preterm Birth and Low Birth Weight after In Utero Exposure to Antiretrovirals Initiated during Pregnancy in Yaoundé, Cameroon.

BACKGROUND: Effects of antiretroviral therapy (ART) on birth outcomes remain controversial. OBJECTIVE: To assess the impact of antenatal exposure to ART on the occurrence of preterm birth (PTB) and low birth weight (LBW). METHODS: A cross-sectional study conducted at the Essos Hospital Center in Yaounde from 2008 to 2011 among HIV vertically exposed infants with two distinct maternal antiretroviral experiences: monotherapy group (Zidovudine, ZDV) and the combination ART group (cART). Mothers already receiving cART before pregnancy were ineligible. In both groups, events of PTB (<37 weeks) and LBW (<2,500g) were analyzed using univariate and multivariate logistic regression; with p<0.05 considered statistically significant. RESULTS: Of the 760 infants, 481 were born from cART-exposed mothers against 279 from maternal-ZDV. Median maternal CD4 count was 378 [interquartile range (IQR): 253-535] cells/mm3. Median duration of ART at onset of delivery was 13 [IQR: 10-17] weeks. In the cART-group, 64.9% (312/481) of mothers were exposed to Zidovudine/Lamuvidine/Nevirapine and only 2% (9/481) were on protease inhibitor-based regimens. Events of PTB were not significantly higher in the cART-group compared to the ZDV-group (10.2% vs. 6.4% respectively, p = 0.08), while onsets of LBW were significantly found in the cART-group compared to ZDV-group (11.6% vs. 7.2% respectively, p = 0.05). Other factors (parity, maternal age at delivery or CD4 cell count) were not associated with PTB. CONCLUSION: cART, initiated during pregnancy, would be an independent factor of LBW. In the era of option B+ (lifelong ART to all HIV-pregnant women), further studies would guide towards measures limiting onsets of LBW.

HBV immunization and vaccine coverage among hospitalized children in Cameroon, Central African Republic and Senegal: a cross-sectional study.

BACKGROUND: Hepatitis B is a major health concern in Africa. The vaccine against hepatitis B virus (HBV) was introduced into the Expanded Programme on Immunization (EPI) of Cameroon and Senegal in 2005, and of CAR (Central African Republic) in 2008. A cross-sectional study was conducted to assess HBV immunization coverage following the vaccine's introduction into the EPI and factors associated with having been vaccinated. METHODS: All hospitalized children, regardless of the reasons for their hospitalization, between 3 months and 6 years of age, for whom a blood test was scheduled during their stay and whose condition allowed for an additional 2 mL blood sample to be taken, and who provided the parent's written consent were included. All children anti-HBs- and anti-HBc + were tested for HBsAg. Vaccination coverage was assessed in three different ways: immunization card, maternal recall and serologic anti-HBs profile. RESULTS: 1783 children were enrolled between April 2009 and May 2010. An immunization card was only available for 24 % of the children. The median age was 21 months. Overall HBV immunization coverage based on immunization cards was 99 %, 49 % and 100 % in Cameroon, CAR and Senegal, respectively (p < 0,001). The immunization rate based on maternal recall was 91 %, 17 % and 88 % in Cameroon, CAR and Senegal, respectively (p < 0,001). According to serology (anti-HBs titer ≥ 10 mUI/mL and anti-HBc-), the coverage rate was 68 %, 13 % and 46 % in Cameroon, CAR and Senegal, respectively (p < 0,001). In Senegal and Cameroon, factors associated with having been vaccinated were: mother's higher education (OR = 2.2; 95 % CI [1.5-3.2]), no malnutrition (OR = 1.6; 95 % CI [1.1-2.2]), access to flushing toilets (OR = 1.6; 95 % CI [1.1-2.3]), and < 24 months old (OR = 2.1; 95 % CI [1.3-3.4] between 12 and 23 months and OR = 2.7; 95 % CI [1.6-4.4] < 12 months). The prevalence of HBV-infected children (HBsAg+) were 0.7 %, 5.1 %, and 0.2 % in Cameroon, CAR and Senegal, respectively (p < 0.001). CONCLUSIONS: Assessing immunization coverage based on immunization cards, maternal recall or administrative data could be usefully reinforced by epidemiological data combined with immunological profiles. Serology-based studies should be implemented regularly in African countries, as recommended by the WHO. Malnutrition, lack of maternal education and poverty are factors associated with vaccine non-compliance. The countries' vaccination programs should actively address these problems.

Different factors associated with loss to follow-up of infants born to HIV-infected or uninfected mothers: observations from the ANRS 12140-PEDIACAM study in Cameroon.

BACKGROUND: Loss to follow-up (LTFU) is a cause of potential bias in clinical studies. Differing LTFU between study groups may affect internal validity and generalizability of the results. Understanding reasons for LTFU could help improve follow-up in clinical studies and thereby contribute to goals for prevention, treatment, or research being achieved. We explored factors associated with LTFU of mother-child pairs after inclusion in the ANRS 12140-Pediacam study. METHODS: From November 2007 to October 2010, 4104 infants including 2053 born to HIV-infected mothers and 2051 born to HIV-uninfected mothers matched individually on gender and study site were enrolled during the first week of life in three referral hospitals in Cameroon and scheduled for visits at 6, 10 and 14 weeks of age. Visits were designated 1, 2 and 3, in chronological order, irrespective of the child's age at the time of the visit. Mother-child pairs were considered lost to follow-up if they never returned for a clinical visit within the first six months after inclusion. Uni- and multivariable logistic regression were adjusted on matching variables to identify factors associated with LTFU according to maternal HIV status. RESULTS: LTFU among HIV-unexposed infants was four times higher than among HIV-exposed infants (36.7% vs 9.8%, p < 0.001). Emergency caesarean section (adjusted Odds Ratio (aOR) = 2.46 95% Confidence Interval (CI) [1.47-4.13]), young maternal age (aOR = 2.29, 95% CI [1.18-4.46]), and absence of antiretroviral treatment for prophylaxis (aOR = 3.45, 95% CI [2.30-5.19]) were independently associated with LTFU among HIV-exposed infants. Factors associated with LTFU among HIV-unexposed infants included young maternal age (aOR = 1.96, 95% CI [1.36-2.81]), low maternal education level (aOR = 2.77, 95% CI [1.95-3.95]) and housewife/unemployed mothers (aOR = 1.56, 95% CI [1.16-2.11]). CONCLUSION: Failure to return for at least one scheduled clinical visit is a problem especially among HIV-unexposed infants included in studies involving HIV-exposed infants. Factors associated with this type of LTFU included maternal characteristics, socio-economic status, quality of antenatal care and obstetrical context of delivery. Enhanced counselling in antenatal and intrapartum services is required for mothers at high risk of failure to return for follow-up visits.

Evaluating the performance of a rapid antigen test for the detection of influenza virus in clinical specimens from children in Cameroon.

The performance of SD Bioline rapid antigen test (RAT) was evaluated using real-time reverse transcription polymerase chain reaction (rRT-PCR) as gold standard. A total of 718 nasal swabs, including 102 rRT-PCR positive and 616 rRT-PCR negative swabs, were tested. RAT demonstrates a sensitivity of 29·4% with a specificity of 100%. The positivity rate of RAT was highly associated with lower cycle threshold (Ct) values (P < 0·0001). The excellent specificity of the RAT allowed for the rapid identification of influenza cases. However, negative results should be verified by rRT-PCR test because of limitations observed in sensitivity.

Drug resistance among drug-naive and first-line antiretroviral treatment-failing children in Cameroon.

BACKGROUND: Scale-up to antiretroviral therapy (ART) requires surveillance for HIV drug resistance. With the goal of attaining 100% pediatric ART coverage in Cameroon, strategies to limit the spread of HIV resistance among children are very important. METHODS: From June 2009 through February 2011, 92 HIV-1-infected children (41 ART-naive, 51 failing first-line ART) living in Yaoundé, Cameroon, were enrolled; HIV-1 Prot-RT genotypic resistance testing (GRT) was performed using an inhouse assay. Among 40 children failing first-line ART, treatment response was evaluated at weeks 24 and 48 after treatment was changed, based on GRT results. RESULTS: The mean age was 72 months both for children who were drug-naive and those failing ART (range: 3-144 and 12-144, respectively), with a mean viremia of 5.59 log and 4.71 log RNA copies/mL, a median CD4 of 17% (588 cells/µL) and 23% (719 cells/µL), respectively. Median time-to-treatment failure was 610 days. A prevalence of 4.9% and 90% drug resistance was observed, respectively, among children who were drug-naive and those failing first-line ART, with circulating recombinant form CRF02_AG as the most prevalent clade (58.6% and 62%, respectively). After a change to GRT-based treatment, more than 90% of children had viremia <3 log RNA copies/mL at week 24 and confirmed at week 48, with 70% achieving undetectable viremia, although without correlation to immune response; 97.5% had switched to lopinavir/ritonavir-containing regimens. CONCLUSION: HIV-1 drug resistance was low among ART-naive children and very high among those failing first-line ART. Treatment change based on GRT was successful for most children, with lopinavir/ritonavir regimens being very promising for second-line use.

Reference values of lymphocyte subsets in healthy, HIV-negative children in Cameroon.

Lymphocyte subset reference values used to monitor infectious diseases, including HIV/AIDS, tuberculosis, malaria, or other immunological disorders in healthy children in Cameroon, are lacking. Values for Caucasian cohorts are already being utilized for clinical decisions but could be inappropriate for African populations. We report here the immunological profile for children aged from birth through 6 years in Cameroon and also compare our values to data from other African and Caucasian populations. In a cohort of 352 healthy children, aged 0 to 6 years, the relative and absolute numbers of T-cell subsets, B cells, and NK lymphocytes were determined from peripheral blood collected in EDTA tubes. Samples were stained with BD Multitest reagents in Trucount tubes and analyzed by using CellQuest-Pro and FlowJo software. We evaluated about 23 different lymphocyte subsets in which the absolute number and percentage values differed significantly (P < 0.05) with age and peaked between 6 and 12 months. B-cell values were higher compared to reported values from developed countries. Differences in activated and differentiated T cells were observed in subjects between 1 and 6 years of age. The absolute CD8(+) T-cell count and the CD4(+)/CD8(+) ratio seem to depend on gender. Normal lymphocyte subsets values among children from Cameroon differ from reported values in Caucasian and some African populations. The differences observed could be due to genetic and environmental factors coupled with the methodology used. These values could be used as initial national reference guidelines as more data are assembled.