Programme quality indicators of HIV drug resistance among adolescents in urban versus rural settings of the centre region of Cameroon.

BACKGROUND: The high rate of mortality among HIV-vertically infected adolescents might be favoured by HIV drug resistance (HIVDR) emergence, which calls for timeous actions in this underserved population. We thus sought to evaluate program quality indicators (PQIs) of HIVDR among HIV-vertically infected adolescents on antiretroviral therapy (ART). METHODS: A study was conducted in the Centre region of Cameroon among adolescents (10-19 years) receiving ART in two urban (The Mother-Child Centre of the Chantal BIYA Foundation, the National Social Welfare Hospital) and three rural (Mfou District Hospital, Mbalmayo District Hospital and Nkomo Medical Center) health facilities. Following an exhaustive sampling from ART registers, patient medical files and pharmacy records, data was abstracted for seven PQIs: on-time drug pick-up; retention in care; pharmacy stock outs; dispensing practices; viral load coverage; viral suppression and adequate switch to second-line. Performance in PQIs was interpreted following the WHO-recommended thresholds (desirable, fair and/or poor); with p < 0.05 considered significant. RESULTS: Among 967 adolescents (888 urban versus 79 rural) registered in the study sites, validated data was available for 633 (554 in urban and 79 in rural). Performance in the urban vs. rural settings was respectively: on-time drug pick-up was significantly poorer in rural (79% vs. 46%, p = 0.00000006); retention in care was fair in urban (80% vs. 72%, p = 0.17); pharmacy stock outs was significantly higher in urban settings (92% vs. 50%, p = 0.004); dispensing practices was desirable (100% vs. 100%, p = 1.000); viral load coverage was desirable only in urban sites (84% vs. 37%, p < 0.0001); viral suppression was poor (33% vs. 53%, p = 0.08); adequate switch to second-line varied (38.1% vs. 100%, p = 0.384). CONCLUSION: Among adolescents on ART in Cameroon, dispensing practices are appropriate, while adherence to ART program and viral load coverage are better in urban settings. However, in both urban and rural settings, pharmacy stock outs, poor viral suppression and inadequate switch to second-line among adolescents require corrective public-health actions to limit HIVDR and to improve transition towards adult care in countries sharing similar programmatic features.

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.

Lifestyle and the presence of helminths is associated with gut microbiome composition in Cameroonians.

BACKGROUND: African populations provide a unique opportunity to interrogate host-microbe co-evolution and its impact on adaptive phenotypes due to their genomic, phenotypic, and cultural diversity. We integrate gut microbiome 16S rRNA amplicon and shotgun metagenomic sequence data with quantification of pathogen burden and measures of immune parameters for 575 ethnically diverse Africans from Cameroon. Subjects followed pastoralist, agropastoralist, and hunter-gatherer lifestyles and were compared to an urban US population from Philadelphia. RESULTS: We observe significant differences in gut microbiome composition across populations that correlate with subsistence strategy and country. After these, the variable most strongly associated with gut microbiome structure in Cameroonians is the presence of gut parasites. Hunter-gatherers have high frequencies of parasites relative to agropastoralists and pastoralists. Ascaris lumbricoides, Necator americanus, Trichuris trichiura, and Strongyloides stercoralis soil-transmitted helminths ("ANTS" parasites) significantly co-occur, and increased frequency of gut parasites correlates with increased gut microbial diversity. Gut microbiome composition predicts ANTS positivity with 80% accuracy. Colonization with ANTS, in turn, is associated with elevated levels of TH1, TH2, and proinflammatory cytokines, indicating an association with multiple immune mechanisms. The unprecedented size of this dataset allowed interrogation of additional questions-for example, we find that Fulani pastoralists, who consume high levels of milk, possess an enrichment of gut bacteria that catabolize galactose, an end product of lactose metabolism, and of bacteria that metabolize lipids. CONCLUSIONS: These data document associations of bacterial microbiota and eukaryotic parasites with each other and with host immune responses; each of these is further correlated with subsistence practices.

Monitoring HIV Drug Resistance Early Warning Indicators in Cameroon: A Study Following the Revised World Health Organization Recommendations.

BACKGROUND: The majority (>95%) of new HIV infection occurs in resource-limited settings, and Cameroon is still experiencing a generalized epidemic with ~122,638 patients receiving antiretroviral therapy (ART). A detrimental outcome in scaling-up ART is the emergence HIV drug resistance (HIVDR), suggesting the need for pragmatic approaches in sustaining a successful ART performance. METHODS: A survey was conducted in 15 ART sites of the Centre and Littoral regions of Cameroon in 2013 (10 urban versus 05 rural settings; 8 at tertiary/secondary versus 7 at primary healthcare levels), evaluating HIVDR-early warning indicators (EWIs) as-per the 2012 revised World Health Organization's guidelines: EWI1 (on-time pill pick-up), EWI2 (retention in care), EWI3 (no pharmacy stock-outs), EWI4 (dispensing practices), EWI5 (virological suppression). Poor performance was interpreted as potential HIVDR. RESULTS: Only 33.3% (4/12) of sites reached the desirable performance for "on-time pill pick-up" (57.1% urban versus 0% rural; p<0.0001) besides 25% (3/12) with fair performance. 69.2% (9/13) reached the desirable performance for "retention in care" (77.8% urban versus 50% rural; p=0.01) beside 7.7% (1/13) with fair performance. Only 14.4% (2/13) reached the desirable performance of "no pharmacy stock-outs" (11.1% urban versus 25% rural; p=0.02). All 15 sites reached the desirable performance of 0% "dispensing mono- or dual-therapy". Data were unavailable to evaluate "virological suppression" due to limited access to viral load testing (min-max: <1%-15%). Potential HIVDR was higher in rural (57.9%) compared to urban (27.8%) settings, p=0.02; and at primary (57.9%) compared to secondary/tertiary (33.3%) healthcare levels, p=0.09. CONCLUSIONS: Delayed pill pick-up and pharmacy stock-outs are major factors favoring HIVDR emergence, with higher risks in rural settings and at primary healthcare. Retention in care appears acceptable in general while ART dispensing practices are standard. There is need to support patient-adherence to pharmacy appointments while reinforcing the national drug supply system.