Effect of Hepatitis B Vaccination on HBV-infection among school children in Yaounde ten years after its introduction of the HBV vaccine into routine Immunization Program in Cameroon

Introduction: since the introduction of the anti-HBV vaccine into the Expanded Program on Immunization (EPI) in 2005 in Cameroon, vaccination coverage has reached 99.0%. This coverage would indicate an increase the number of children immune to Hepatitis B Virus (HBV) and a decrease in susceptibility to HBV-infection. This study was conducted to evaluate the effect of the HBV vaccine on pediatric HBV-infection in Yaounde, Cameroon. Methods: this school based cross-sectional study was conducted from February to May 2016 among 180 children from Nkomo public school. The study population was stratified into two groups: vaccinated (n=95) versus (vs) unvaccinated (n=85). Screening for HBV biomarkers was done using a rapid panel test for detection (HBsAg, HBeAg and anti-HBc) and anti-HBs titer using enzyme linked immunosorbent assay (ELISA). Statistical analyses were done using SPSS v. 22 with p ≥0.05 considered significant. Results: the mean age was 9.65 years. HBsAg (p=0.019) and anti-HBc (p=0.001) rates were detected in children aged ≥10 years and children aged < 10 years (95.95% [71/74]) were vaccinated vs 22.64% (24/106) for those aged ≥10 years (OR: 80.86; 95% CI: 23.36%-279.87%, p < 0.0001). According to anti-HBV vaccination status, HBsAg rate varied from [9.41% (8/85) to 1.05% (1/95), p=0.025], HBeAg rate varied from [2.35% (2/85) to 0% (0/95), p= 0.42] and anti-HBc rate ranged from [12.94% (11/85) to 2.10% (2/95), p= 0.011]. Conclusion: despite the variability of the anti-HBs titer, vaccination against HBV has a positive effect on the reduction of HBV infection in children in tropical settings such as Cameroon.

Determinants of survival of adolescents receiving antiretroviral therapy in the Centre Region of Cameroon: a multi-centered cohort-analysis.

BACKGROUND: In spite of the global decreasing mortality associated with HIV, adolescents living with HIV (ADLHIV) in sub-Saharan Africa still experience about 50% mortality rate. We sought to evaluate survival rates and determinants of mortality amongst ADLHIV receiving antiretroviral therapy (ART) in urban and rural settings. METHODS: A multi-centered, 10-year retrospective, cohort-study including ADLHIV on ART ≥ 6 months in the urban and rural settings of the Centre Region of Cameroon. Socio-demographic, clinical, biological, and therapeutic data were collected from files of ADLHIV. The Kaplan-Meier method was used to estimate survival probability after ART initiation; the log rank test used to compare survival curves between groups of variables; and the Cox proportional hazard model was used to identify the determinants of mortality. RESULTS: A total of 403 adolescents' records were retained; 340 (84%) were from the urban and 63 (16%) from the rural settings. The female to male ratio was 7:5; mean age (Standard deviation) was 14.1 (2.6) years; at baseline, 64.4% were at WHO clinical stages I/II, 34.9% had ≥ 500 CD4 cells/mm3, 91.1% were anemic, and the median [Inter Quartile Range] duration on ART was5.3 [0.5-16] years. The survival rate at 1, 5 and 10 years on ART was respectively 97.0%, 55.9% and 8.7%; with mean survival time of 5.8 years (95% CI 5.5-6.1). In bivariate analysis, living in the rural setting, non-disclosed HIV status, baseline CD4 count < 500 cells/mm3, not being exposed to nevirapine prophylaxis at birth and being horizontally infected were found to be the determinants of higher mortality with poor retention in care slightly associated with mortality. In multivariate analysis, living in rural settings, poor retention in care and anemia were independent predictors of mortality (p < 0.05). CONCLUSION: Although ADLHIV have good survival rate on ART after 1 year, we observe poor survival rates after 5 years and especially 10 years of treatment experience. Mitigating measures against poor survival should target those living in rural settings, anemic at baseline, or experiencing poor retention in care.

Epidemiology of emergency and elective caesarean section and its association with early neonatal mortality in sub-Saharan African countries.

INTRODUCTION: Investigating elective and emergency caesarean section (CS) separately is important for a better understanding of birth delivery modes in the sub-Saharan Africa (SSA) region and identifying bottlenecks that prevent favourable childbirth outcomes in SSA. This study aimed at evaluating the prevalences of both CS types, determining their associated socioeconomic factors and their association with early neonatal mortality in SSA. METHODS: SSA countries Demographic and Health Surveys data that had collected information on the CS' timing were included in our study. A total of 21 countries were included in this study, with a total of 155 172 institutional live births. Prevalences of both CS types were estimated at the countries' level using household sampling weights. Multilevel models were fitted to identify associated socioeconomic factors of both CS types and their associations with early neonatal mortality. RESULTS: The emergency CS prevalence in SSA countries was estimated at 4.6% (95% CI 4.4-4.7) and was higher than the elective CS prevalence estimated at 3.4% (95% CI 3.3-3.6). Private health facilities' elective CS prevalence was estimated at 10.2% (95% CI 9.3-11.2) which was higher than the emergency CS prevalence estimated at 7.7% (95% CI 7.0-8.5). Conversely, in public health facilities, the emergency CS prevalence was estimated at 4.0% (95% CI 3.8-4.2) was higher than the elective CS prevalence estimated at 2.7% (95% CI 2.6-2.8). The richest women were more likely to have birth delivery by both CS types than normal vaginal delivery. Emergency CS was positively associated with early neonatal mortality (adjusted OR=2.37, 95% CI 1.64-3.41), while no association was found with elective CS. CONCLUSIONS: Findings suggest shortcomings in pregnancy monitoring, delivery preparation and postnatal care. Beyond antenatal care (ANC) coverage, more attention should be put on quality of ANC, postnatal care, emergency obstetric and newborn care for favourable birth delivery outcomes in SSA.

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.

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.

Mother-to-Child Transmission of HIV Through Breastfeeding Improving Awareness and Education: A Short Narrative Review.

Despite critical progress registered in the reduction of mother to child transmission (MTCT) of HIV worldwide, transmission through breastfeeding still contributes to almost 50% of pediatric HIV infections recorded every year. In this short narrative review, after development of an extensive background on HIV and breastfeeding, some directions are suggested to address the key bottlenecks. Specifically, reinforcing the prevention of MTCT through breastfeeding (BF) in order to move towards elimination of MTCT prior to 2030 may require, among others strategies: tracking all women of child bearing age through HIV testing, improving testing and retesting of women during pregnancy and breastfeeding, strengthening adherence on antiretroviral therapy (ART) among pregnant and lactating women, ensuring continuum and retention in care of mother and baby-pairs up to 24 months, switching ART in non-viral suppressed mothers after improvement of adherence counseling. In addition, due to the burden of seroconversion during pregnancy or thereafter through BF, pre-exposure prophylaxis (PreP) for most at risk women should be implemented urgently. The opportunity to extend the infant prophylaxis to the whole lactating period should be assessed to address residual transmission amongst viral suppressed mothers.

Archiving of mutations in HIV-1 cellular reservoirs among vertically infected adolescents is contingent with clinical stages and plasma viral load: Evidence from the EDCTP-READY study.

INTRODUCTION: Globally, HIV-related adolescent deaths have increased about 50%, especially for those who are vertically infected. This could be driven by archived drug resistance mutations (DRMs) as children grow up, which might jeopardize antiretroviral therapy (ART). Our objective was to compare HIV-1 genotypic variation between plasma RNA and proviral DNA of vertically infected adolescents (aged 10-19 years) failing ART. METHODS: A comparative study was conducted in 2019 among 296 adolescents with perinatal HIV infection (ALPHI) failing ART in health facilities of the Centre Region of Cameroon. The WHO clinical stage, CD4 count and plasma viral load (PVL) were measured. For those failing ART (PVL ≥ 1000 copies/mL), RNA (plasma) and proviral DNA (buffy coat) were sequenced in the pol gene at Chantal BIYA International Reference Centre (CIRCB), Yaoundé, Cameroon. HIV-1 subtypes and DRMs were interpreted using Stanford HIVdb v.8.8 and MEGA-X. RESULTS: Of the 30% (89/296) failing ART, 81 had both RNA and DNA sequences generated and three were excluded for APOBEC mutations: the mean age was 16 ± 3 years; female-to-male ratio was 3:5; median PVL was 46 856 copies/mL [interquartile range (IQR): 19 898-271 410]; median CD4 count was 264 cells/µL (IQR: 131-574); and 42% were at WHO clinical stage 3/4. Subtype concordance between RNA and DNA viral strains was 100%, with CRF02_AG being predominant (65%) and two potential new recombinants found (A1/G/K; F1/G). Adolescents with DRMs were significantly higher in plasma than in proviral DNA (92% vs. 86%, p < 0.0001). Prevalent DRMs by drug class (RNA vs. DNA respectively) were at position M184 (74% vs. 67%) for nucleoside reverse transcriptase inhibitors (NRTIs), K103 (63% vs. 59%) for non-NRTIs, and V82, L76 and M46 (2% vs. 2%) for protease inhibitors. A total of 35% (27/78) of adolescents had concordant DRM profiles in RNA and DNA, while 27% (21/78) had DRMs only in proviral DNA. The presence of archived DRMs was associated with advanced clinical stage 3/4 (OR = 0.14, p = 0.0003) and PVL < 5 Log (Copies/mL) (OR: 4.88, p = 0.006). CONCLUSIONS: Although plasma RNA remains more sensitive for detecting HIV-1 DRMs, about a quarter of ALPHI experiencing ART failure in an African setting might have archived DRMs in viral reservoirs, indicating clinically occult resistance. Thus, to ensure effective ART success, proviral DNA profiling (alongside RNA genotyping) would provide additional DRMs for adolescents with advanced clinical stages and/or moderate PVL.

Determinants of switch to paediatric second-line antiretroviral therapy after first-line failure in Cameroon.

OBJECTIVE: With scale-up of antiretroviral therapy (ART) children, treatment failure and switch to subsequent ART regimens are common. Our objectives were to evaluate switching practices and identify factors associated among children and adolescents failing their first-line ART. METHODS: A facility-based survey study was conducted in a cohort of children living with HIV experiencing virological failure (VF) at the Essos Hospital Centre of Yaounde, Cameroon. Data were collected using a standard questionnaire, and key variables were as follows: (a) VF defined as viral load (VL) > 1000 copies/ml, (b) rate of switch to second-line and (c) reason(s) for switching ART. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the association between study variables, and P < 0.05 was considered statistically significant. RESULTS: A total of 106 children experiencing VF were enrolled: median age was 8 [interquartile range (IQR): 3-15] years; 60.38% were boys and 39.62% were orphans of one/both parents. A proportion of 69% were at the WHO clinical stage III/IV, and 13.21% were experiencing immunological failure (CD4 < 200 cells/mm3 ). The median duration on first-line ART was 36 [IQR: 7-157] months prior to detecting VF, and the rate of switch to second-line ART was 70.75% (75/106). Delay in switching ART after a confirmed VF was 11 [IQR: 7-16] months. After switch to second-line ART, the median time to achieve undetectable VL (<40 copies/ml) was 14 [IQR: 9-21] months. Multivariate analysis revealed that only children with viral rebound (aOR = 0.09; 95% CI = 0.03-0.24) were less likely to be switched. Of note, being orphaned (aOR = 0.35, CI = 0.11-1.11), biological sex (aOR = 1.77, CI = 0.60-5.29) and immune status (aOR = 0.19, CI = 0.03-1.31, 0.09) had no significant effect on switching to second-line ART. CONCLUSION: In this paediatric population experiencing VF after about 3-4 years from ART initiation, the majority are switched to second-line ART after a delay of almost one year. Delayed switch to second-line was driven essentially by viral rebound, underscoring the need for close viral monitoring.

Evaluation of treatment response, drug resistance and HIV-1 variability among adolescents on first- and second-line antiretroviral therapy: a study protocol for a prospective observational study in the centre region of Cameroon (EDCTP READY-study).

BACKGROUND: Sub-Saharan Africa (SSA) alone has nine out of every 10 children living with HIV globally and monitoring in this setting remains suboptimal, even as these children grow older. With scalability of antiretroviral therapy (ART), several HIV-infected children are growing towards adolescence (over 2.1 million), with the potentials to reach adulthood. However, despite an overall reduction in HIV-related mortality, there are increasing deaths among adolescents living with HIV (ADLHIV), with limited evidence for improved policy-making. Of note, strategies for adolescent transition from pediatrics to adult-healthcare are critical to ensure successful treatment response and longer life expectancy. Interestingly, with uptakes in prevention of mother-to-child transmission, challenges in ART programs, and high viremia among children in SSA, the success rate of paediatric ART might be quickly jeopardised, with possible HIV-1 drug-resistance (HIVDR) emergence, especially after years of paediatric ART exposure. Therefore, monitoring ART response in adolescents and evaluating HIVDR patterns might limit disease progression and guide on subsequent ART options for SSA ADLHIV. OBJECTIVES: Among Cameroonian ADLHIV receiving ART, we shall evaluate the rate of immunovirologic failure, acquired HIVDR-associated mutations, HIV-1 subtype distribution, genetic variability in circulating (plasma) versus archived (cellular) viral strains, and HIVDR early warning indicators (EWIs) at different time-points. METHODS: A prospective and observational study will be conducted among 250 ADLHIV (10-19 years old) receiving ART in the centre region of Cameroon, and followed-up at 6 and 12 months after enrollment. Following consecutive sampling at enrolment, plasma viral load and CD4/CD8 count will be measured, and genotypic resistance testing (GRT) will be performed both in plasma and in buffy coat for participants experiencing virological failure (two consecutive viremia > = 1000 copies/ml). Plasma viral load and CD4/CD8 will be monitored for all participants at 6 and 12 months after enrolment. HIVDR-EWIs will be monitored and survival analysis performed during the 12 months follow-up. Primary outcomes are rates of virological failure, acquired-HIVDR, and mortality. DISCUSSION: Our findings will provide evidence-based recommendations to ensure successful transition from paediatrics to adult ART regimens and highlight further needs of active ART combinations, for reduced morbidity and mortality in populations of ADLHIV within SSA.

Outcomes of protease inhibitor-based antiretroviral therapy amongst children and associated-factors in Yaoundé, Cameroon.

BACKGROUND: There are limited data on protease inhibitor (PI)-based antiretroviral therapy (ART) amongst children in resource-limited settings, for informing on optimal paediatric regimens. OBJECTIVE: To evaluate therapeutic response to PI-based ART amongst HIV-infected Cameroonian children. METHODS: A retrospective study was conducted amongst children aged 2-18 years receiving a PI-based ART at the Essos Hospital Centre (EHC), Yaounde, Cameroon. Primary end points were therapeutic success on PI-based ART, defined as clinical success (WHO I/II clinical stage), immunological success (CD4 ≥ 500/mm3) and viral suppression (viral load [VL]<1000 copies/ml). Factors associated with therapeutic success were assessed in uni- and multivariate analysis using SPSS software v.2.0; with p<0.05 considered statistically significant. RESULTS: A total of 71 eligible children on PI-based ART were enrolled (42 on initial and 29 on substituted regimens), with a median age of 8 [IQR: 5-12] years and mean duration on ART of 7 years. Following therapeutic responses, all (100%) experienced clinical success, 95.2% experienced immunological success (91.7% on initial and 97.2% on substituted PI/r-based regimens) and 74.7% viral suppression. In univariate analysis, viral suppression was associated with: younger age (p<0.0001), living with parents as opposed to guardians (p = 0.049), and the educational level (p<0.0001). In multivariate analysis, only the age ranges of 10-14 years (OR: 0.22 [0.07-0.73]) and 15-18 years (OR: 0.08 [0.02-0.57]), were determinants of poor viral suppression. CONCLUSION: Among these Cameroonian children, PI-based ART confers favourable clinical and immunological outcomes. The poor rate of viral suppression was mainly attributed to adolescence (10-18 years).

HIV-1 transmission and survival according to feeding options in infants born to HIV-infected women in Yaoundé, Cameroon.

BACKGROUND: Evidence of 24-months survival in the frame of prevention of mother-to-child transmission (PMTCT) cascade-care is scare from routine programs in sub-Saharan African (SSA) settings. Specifically, data on infant outcomes according to feeding options remain largely unknown by month-24, thus limiting its breath for public-health recommendations toward eliminating new pediatric HIV-1 infections and improving care. We sought to evaluate HIV-1 vertical transmission and infant survival rates according to feeding options. METHODS: A retrospective cohort-study conducted in Yaounde from April 2008 through December 2013 among 1086 infants born to HIV-infected women and followed-up throughout the PMTCT cascade-care until 24-months. Infants with documented feeding option during their first 3 months of life (408 on Exclusive Breastfeeding [EBF], 663 Exclusive Replacement feeding [ERF], 15 mixed feeding [MF]) and known HIV-status were enrolled. HIV-1 vertical transmission, survival and feeding options were analyzed using Kaplan Meier Survival Estimate, Cox model and Schoenfeld residuals tests, at 5% statistical significance. RESULTS: Overall HIV-1 vertical transmission was 3.59% (39), and varied by feeding options: EBF (2.70%), ERF (3.77%), MF (20%), p = 0.002; without significance between EBF and ERF (p = 0.34). As expected, HIV-1 transmission also varied with PMTCT-interventions: 1.7% (10/566) from ART-group, 1.9% (8/411) from AZT-group, and 19.2% (21/109) from ARV-naïve group, p < 0.0001. Overall mortality was 2.58% (28), higher in HIV-infected (10.25%) vs. uninfected (2.29%) infants (p = 0.016); with a survival cumulative probability of 89.3% [79.9%-99.8%] vs. 96.4% [94.8%-97.9% respectively], p = 0.024. Mortality also varied by feeding option: ERF (2.41%), EBF (2.45%), MF (13.33%), p = 0.03; with a survival cumulative probability of 96% [94%-98%] in ERF, 96.4% [94.1%-98.8%] in EBF, and 86.67% [71.06%-100%] in MF, p = 0.04. Using Schoenfeld residuals test, only HIV status was a predictor of survival at 24 months (hazard ratio 0.23 [0.072-0.72], p = 0.01). CONCLUSION: Besides using ART for PMTCT-interventions, practice of MF also drives HIV-1 vertical transmission and mortality among HIV-infected children. Thus, throughout PMTCT option B+ cascade-care, continuous counseling on safer feeding options would to further eliminating new MTCT, optimizing response to care, and improving the life expectancy of these children in high-priority countries.

Immuno-virological response and associated factors amongst HIV-1 vertically infected adolescents in Yaoundé-Cameroon.

INTRODUCTION: Limited studies have reported the outcomes of lifelong antiretroviral therapy (ART) amongst adolescents living with HIV (ALWHIV) in resource-limited settings (RLS), thus classifying this population as underserved. We therefore aimed to ascertain the immunological and virological responses, and associated factors amongst Cameroonian ALWHIV. METHOD: A cross-sectional and observational study was conducted from January through May 2016 at the National Social Insurance Fund Health Centre in Yaoundé-Cameroon. Immunological and virological responses were evaluated using CD4 cell count and viral load respectively, with viral suppression (VS) defined as <50 copies/ml. Adherence was evaluated using self-reported missing doses during the past 14 days. Data were analyzed using R v.3.3.0, with p<0.05 considered statistically significant. RESULTS: Of the 145 ALWHIV on ART enrolled in the study, 52% were female, median age [interquartile (IQR)] was 13 [11-16] years, median [IQR] time-on-ART was 7 [5-10] years, 48% were orphans, 92% were on first-line ART and 36% were adherent to ART. Following ART response, 79% (114/145) had CD4 ≥500/mm3, 71.0% (103/145) were on VS of whom 52.4% (76/145) had a sustained VS. Duration of ART was associated with immune restoration (Odd Ratio 3.73 [1.26-12.21]) but not with virological response. Risks of poor adherence were greater in orphans of both parents (p = 0.078). CONCLUSION: In this urban setting of Cameroon, ALWHIV receiving ART show favorable immunological and virological response in a medium run. For long-term ART success, implementing a close monitoring of adherence and risks of viral rebound would be highly relevant, especially for orphans of both parents.

Predictors of Virologic Failure on First-line Antiretroviral Therapy Among Children in a Referral Pediatric Center in Cameroon.

BACKGROUND: Suboptimal response to antiretroviral therapy (ART) is common among children living with HIV (CLHIV) in resource-limited settings. We sought to assess virologic failure (VF), time for switching to second-line regimens and factors associated with VF in CLHIV receiving first-line ART in Cameroon. METHODS: An observational cohort study was conducted in 375 CLHIV initiating a first-line ART and treated for ≥6 months at the National Social Insurance Fund Hospital in Yaoundé-Cameroon from 2009 to 2013. Using logistic regression, predictors of VF and delayed switch were assessed by univariate and multivariate analysis. P < 0.05 was considered statistically significant. RESULTS: Overall, 17% (64/375) CLHIV experienced VF on first-line ART after a median time of 28 (interquartile range: 22-38) months. After VF, median time to switching from first- to second-line ART was 20 (interquartile range: 8-24) months. In multivariate analysis, VF was associated with male gender (adjusted odds ratio: 0.36; 95% confidence interval: 0.19-0.71; P = 0.003), motherless children (adjusted odds ratio: 2.9; 95% confidence interval: 1.3-6.06; P = 0.005) and treatment with stavudine-containing compared with zidovudine-containing regimens (P = 0.022). Overall, male gender, orphanhood (motherless) and treatment with stavudine-containing regimens predicted VF at a rate of 70% (area under curve =0.70). CONCLUSION: VF on first-line pediatric ART is common, and switching children failing first-line to second-line ART is considerably delayed. These results suggest performance of pediatric ART program can be improved by targeting orphans, adapting counseling for male children, complete phasing-out of stavudine and ensuring timely switch to second-line regimens.

HIV-Infected or -Exposed Children Exhibit Lower Immunogenicity to Hepatitis B Vaccine in Yaoundé, Cameroon: An Appeal for Revised Policies in Tropical Settings?

BACKGROUND: Since 2005, anti-hepatitis B virus (anti-HBV) vaccine is part of the Expanded Program on Immunization (EPI) for infants born in Cameroon, with 99% anti-HBV coverage. In a context of generalized HIV epidemiology, we assessed paediatric anti-HBV vaccine response according to HIV status, feeding option and age in a tropical context. METHODOLOGY: Prospective, observational and cross-sectional study conducted among 82 children (27 [IQR: 9-47] months, min-max: 6-59), after complete anti-HBV vaccination (Zilbrix Hepta: 10µg AgHBs) at the Essos Health Centre in Yaounde, Cameroon, classified as group-A: HIV unexposed (28), group-B: HIV-exposed/uninfected (29), group-C: HIV-infected (25). Quantitative anti-HBs ELISA was interpreted as "no", "low-" or "protective-response" with <1, 1-10, or ≥10 IU/L respectively; with p-value<0.05 considered significant. RESULTS: Children were all HBV-unexposed (AcHBc-negative) and uninfected (HBsAg-negative). Response to anti-HBV vaccine was 80.49% (66/82), with only 45.12% (37/82) developed a protective-response (≥10IU/L). According to HIV status, 60.71% (17/28) developed a protective-response in group-A, vs. 51.72% (15/29) and 20% (5/25) in group-B and group-C respectively, Odds Ratio (OR): 2.627 [CI95% 0.933-7.500], p = 0.041. According to feeding option during first six months of life, 47.67% (21/45) developed a protective-response on exclusive breastfeeding vs. 43.24% (16/37) on mixed or formula feeding, OR: 1.148 [CI95% 0.437-3.026], p = 0.757. According to age, protective-response decreased significantly as children grow older: 58.33% (28/48) <24 months vs. 26.47% (9/34) ≥24 months, OR: 3.889 [CI95% 1.362-11.356], p = 0.004; and specifically 67.65% (23/34) ≤6 months vs. 0%, (0/5) 33-41 months, p = 0.008. CONCLUSIONS: Anti-HBV vaccine provides low rate of protection (<50%) among children in general, and particularly if HIV-exposed, infected and/or older children. Implementing policies for early vaccination, specific immunization algorithm for HIV-exposed/infected children, and monitoring vaccine response would ensure effective protection in tropical settings, pending extensive/confirmatory investigations.

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.

Preventing HIV-1 transmission in breastfed infants in low resource settings: early HIV infection and late postnatal transmission in a routine prevention of mother-to-child transmission program in Yaounde, Cameroon.

OBJECTIVE: To report on overall HIV-transmission rates [early and late postnatal transmission (LPNT)] in breastfed infants born to HIV-positive women. METHODS: Mother-baby pairs in a routine prevention of mother-to-child transmission program. Promotion of exclusive breastfeeding (EBF) coupled with access to antiretroviral treatment (ART) or prevention using antiretroviral (pARV). Early infant diagnosis using HIV-RNA/PCR or HIV-DNA/PCR >6 weeks. LPNT assessed 6 weeks after weaning in infant earlier tested negative. MAIN MEASUREMENT: early HIV infection and LPNT. RESULTS: We included 285 infants for analysis; 89.5 % of mothers were receiving ART or pARV; 86% babies took daily pARV (median duration, 6 weeks). Exclusive breastfeeding (EBF) rate: 96% (median duration, 4 months). The cumulative transmission of HIV-1 was 2.8% at 8 weeks (95% confidence interval: 1.9-3.7). After weaning (abrupt 44%), 3 of 212 infants were HIV infected (1.4%). Nine-month cumulative HIV-transmission rate was 4.2% (1.5-6.9). Incidence of late postnatal HIV infection stood at 1.5/100 child-years of breastfeeding (BF). Cumulative risk of HIV transmission (8 weeks-9 months) was 1%. CONCLUSION: Both promotion of EBF and access to antiretroviral therapy contribute to lower HIV transmission in breastfed infants in low resource settings.

Early outcomes of HIV exposed children in the first district-wide programme using extended regimens for the prevention of mother-to-child transmission of HIV, in Yaounde, Cameroon.

OBJECTIVE: Report on the early outcomes achieved in the prevention of mother-to-child transmission (PMTCT) programme in the Djoungolo Health District using more effective antiretroviral PMTCT regimens. METHODS: Observational cohort of HIV exposed infants. MAIN OUTCOME MEASURE: early infant HIV status and 3-month mortality rate. RESULTS: From March 2008 to March 2010, 587 HIV-positive mother-baby pairs were enrolled and classified according to the following maternal antiretroviral regimen: Group 1: highly active antiretroviral therapy (HAART), Group 2: dual therapy, Group 3: no treatment. 484/587 (82%) underwent HIV-early infant diagnosis at a median age of 7 weeks; 4.5% (95% CI 2.65-6.34) were HIV-infected. HIV transmission rate differed by maternal prophylaxis: 1.7% for HAART, 2.7% for dual therapy and 15.7% for Group 3 (p < 0.001), but not by feeding method (2.74%)-exclusive breastfeeding vs. 5.34% formula (NS). The 3-month mortality rate stands at 1%. CONCLUSIONS: The 4.5% MTCT-rate of HIV-1 reported, confirms the feasibility and effectiveness of a district wide PMTCT programme using HAART in low-income settings.

Virological profile of pregnant HIV positive women with high levels of CD4 count in low income settings: can viral load help as eligibility criteria for maternal triple ARV prophylaxis (WHO 2010 option B)?

INTRODUCTION: The objective of the study was to determine HIV-1 RNA load profile during pregnancy and assess the eligibility for the maternal triple antiretroviral prophylaxis. It was an observational cohort of pregnant HIV positive women ignorant of antiretroviral therapy with CD4 cell count of > 350/mm(3) METHODS: Routine CD4 cell count assessment in HIV positive pregnant women completed by non exclusive measurement of the viral load by PCR /ARN in those with CD4 cell count > 350/mm(3). EXCLUSION CRITERIA: highly active antiretroviral therapy prior to pregnancy. RESULTS: Between January and December 2010, CD4 cell count was systematically performed in all pregnant women diagnosed as HIV-infected (n=266) in a referral center of 25 antenatal clinics. 63% (N=170) had CD4 cell count > 350/mm(3), median: 528 (IQR: 421-625). 145 underwent measurement of viral load by PCR/RNA at a median gestational of 23 weeks of pregnancy (IQR: 19-28). Median viral load 4.4 log(10)/ml, IQR (3.5-4.9).19/145(13%) had an undetectable viral load of = 1.8 log(10)/ml. 89/145(61%) had a viral load of = 4 log(10)/ml and were eligible for maternal triple ARV prophylaxis. CONCLUSION: More than 6 in 10 pregnant HIV positive women with CD4 cell count of > 350/mm(3) may require triple antiretroviral for prophylaxis of MTCT. Regardless of cost, such results are conclusive and may be considered in HIV high burden countries for universal access to triple antiretroviral prophylaxis in order to move towards virtual elimination of HIV MTCT.