Characterization of HIV-1 Reservoirs in Children and Adolescents: A Systematic Review and Meta-Analysis Toward Pediatric HIV Cure.

OBJECTIVE: To conduct a comprehensive, systematic review of the profile of HIV-1 reservoirs in children and adolescents with perinatally acquired HIV infection. STUDY DESIGN: Randomized and nonrandomized trials, cohort studies, and cross-sectional studies on HIV reservoirs in pediatric populations, published between 2002 and 2022, were included. Archived-drug resistance mutations (ADRMs) and the size of reservoirs were evaluated. Subgroup analyses were performed to characterize further the data, and the meta-analysis was done through random effect models. RESULTS: Overall, 49 studies from 17 countries worldwide were included, encompassing 2356 perinatally infected participants (48.83% females). There are limited data on the quantitative characterization of viral reservoirs in sub-Saharan Africa, with sensitive methodologies such as droplet digital polymerase chain reaction rarely employed. The overall prevalence of ADRMs was 37.80% (95% CI 13.89-65.17), with 48.79% (95% CI 0-100) in Africa, 42.08% (95% CI 6.68-82.71) in America, 23.88% (95% CI 14.34-34.90) in Asia, and 20.00% (95% CI 10.72-31.17) in Europe, without any difference between infants and adolescents (P = .656). Starting antiretroviral therapy (ART) before 2 months of age limited the levels of HIV-1 DNA (P = .054). Participants with long-suppressed viremia (>5 years) had lower levels of HIV-1 DNA (P = .027). Pre- and post-ART CD4 ≤29% and pre-ART viremia ≥5Log were all found associated with greater levels of HIV-1 DNA (P = .038, P = .047, and P = .041, respectively). CONCLUSIONS: The pooled prevalence of ADRMs is high in perinatally infected pediatric population, with larger proviral reservoir size driven by delayed ART initiation, a shorter period of viral suppression, and immunovirological failures. Thus, strategies for pediatric HIV functional cure should target children and adolescents with very early ART initiation, immunocompetence, and long-term viral suppression.

Factors associated with the occurrence of maternal deaths in the West Region between 2020 - 2022: case control study.

WHO defines maternal mortality as any death of a woman occurring during pregnancy or within 42 days of its termination or after delivery. Our aim was to study the factors associated with the occurrence of maternal deaths in the West Region of Cameroon between 2020 and 2022. This was a case-control study. Cases consisted of maternal deaths that occurred during the study period. The controls for their part were made up of women who normally gave birth in the same health facilities from which the cases came and during the same period as the cases. The only exposure criterion being the status of death. The data useful for our investigation were collected respectively with the investigation sheets, audit reports and via interviews with the heads of the health facilities where the maternal deaths occurred with a view to considerably reducing information bias. Analysis were done with IBM-SPSS 25 and RStudio 2023.03.0. The West Region of Cameroon recorded 161 maternal deaths between 2020 and 2022. 67% of them were housewives. The most frequently identified causes were haemorrhage (ante-, per- and post-partum), followed far behind by complications and sepsis, with respective 42.2%, 12.4% and 10.6%. Slightly more than one child out of 10 had an abnormal presentation. Nearly 50% had a short labor (less than 10 hours), the partograph was used in 38% of the women, and the GATP practiced in 50.1% of them. Abnormal presentation of the fetus (aOR = 2.7 (95% CI: 1.4 - 5.1), p=0.002), failure to use the partograph (aOR = 4.4 (95% CI: 2 .6 - 7.4), p<0.001), the fact of not having an economic activity (aOR = 1.7 (95% CI: 1.0 - 2.7), p = 0.033), the fact of having taken less than 2 doses of VAT ( aOR = 2.8 (95% CI: 1.8 - 4.4), p<0.001) and the absence of practice of GATP (aOR = 1.6 (CI 95%: 1.0 - 2.6), p=0.040) were identified as factors that significantly favored the occurrence of maternal deaths. Several factors negatively influence the occurrence of maternal deaths in the West Region. Operational strategies such as continuous training of maternity ward staff, and the establishment of systematic maternal death audits and review meetings should be implemented to reduce and control these risk factors.

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.

Evaluation of HIV-1 capsid genetic variability and lenacapavir (GS-6207) drug resistance-associated mutations according to viral clades among drug-naive individuals.

OBJECTIVES: We evaluated the HIV-1 capsid genetic variability and lenacapavir drug resistance-associated mutations (DRMs) among drug-naive individuals across HIV-1 clades. METHODS: A total of 2031 HIV-1 sequences from drug-naive patients were analysed for capsid amino acid modification and the prevalence of lenacapavir DRMs. Amino acid positions with <5% variability were considered as conserved and variability was analysed by HIV-1 clades. RESULTS: Overall, 63% (148/232) of amino acid positions were conserved in the capsid protein. Of note, conservation was consistent in specific binding residues of cellular factors involved in viral replication [CypA (G89, P90), CPSF6 (Q4, N57, N74, A77, K182) and TRIM-NUP153 (R143)], while N183 (12.31%) was the only non-conserved lenacapavir binding residue. The overall prevalence (95% CI) of lenacapavir DRMs was 0.14% (0.05-0.44) (3/2031), with M66I (0.05%) and Q67H (0.05%) observed in subtype C, and T107N (0.05%) observed in CRF01_AE. Moreover, polymorphic mutations M66C (n = 85; 4.18%), Q67K (n = 78; 3.84%), K70R (n = 7; 0.34%), N74R (n = 57; 2.81%) and T107L (n = 82; 4.03%) were observed at lenacapavir resistance-associated positions. CONCLUSIONS: The low level of lenacapavir DRMs (<1%) supports its predicted effectiveness for treatment and prevention, regardless of HIV-1 clades. The established conserved regions hence serve as a hallmark for the surveillance of novel mutations potentially relevant for lenacapavir resistance.

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.

Baseline integrase drug resistance mutations and conserved regions across HIV-1 clades in Cameroon: implications for transition to dolutegravir in resource-limited settings.

BACKGROUND: Transition to dolutegravir-based regimens in resource-limited settings (RLS) requires prior understanding of HIV-1 integrase variants and conserved regions. Therefore, we evaluated integrase drug resistance mutations (DRMs) and conserved regions amongst integrase strand transfer inhibitor (INSTI)-naive patients harbouring diverse HIV-1 clades in Cameroon. METHODS: A cross-sectional study was conducted amongst 918 INSTI-naive patients from Cameroon (89 ART-naive and 829 ART-experienced patients). HIV-1 sequences were interpreted regarding INSTI-DRMs using the Stanford HIVdb v8.9-1 and the 2019 IAS-USA list. Amino acid positions with <1% variability were considered as highly conserved. Subtyping was performed by phylogeny. RESULTS: Overall prevalence (95% CI) of INSTI-DRMs was 0.8% (0.4-1.7), with 0.0% (0.0-4.0) amongst ART-naive versus 0.9% (0.5-1.9) amongst ART-experienced patients; P = 0.44. Accessory mutations (95% CI) were found in 33.8% (30.9-37.0), with 38.2% (28.1-49.1) amongst ART-naive versus 33.4% (30.4-36.7) amongst ART-experienced patients; P = 0.21. Of 288 HIV-1 integrase amino acid positions, 58.3% were highly conserved across subtypes in the following major regions: V75-G82, E85-P90, H114-G118, K127-W132, E138-G149, Q168-L172, T174-V180, W235-A239 and L241-D253. Wide genetic diversity was found (37 clades), including groups M (92.3%), N (1.4%), O (6.2%) and P (0.1%). Amongst group M, CRF02_AG was predominant (47.4%), with a significantly higher frequency (95% CI) of accessory mutations compared with non-AG [41.4% (36.8-46.0) versus 27.1% (23.3-31.2) respectively; P < 0.001]. CONCLUSIONS: The low baseline of INSTI-DRMs (<1%) in Cameroon suggests effectiveness of dolutegravir-based regimens. In spite of high conservation across clades, the variability of accessory mutations between major circulating strains underscores the need for monitoring the selection of INSTI-DRMs while scaling up dolutegravir-based regimens in RLS.

Human immunodeficiency virus is a driven factor of human papilloma virus among women: evidence from a cross-sectional analysis in Yaoundé, Cameroon.

BACKGROUND: Human papillomavirus (HPV) is the leading cause of cervical cancers, causing 270.000 deaths annually worldwide of which 85% occur in developing countries with an increasing risk associated to HIV infection. This study aimed at comparing HPV's positivity and genotype distribution in women according to their HIV status and determinants. METHODS: A comparative study was carried out in 2012 at the Chantal BIYA International Reference Centre (CIRCB) among 278 women enrolled consecutively at the General Hospital and the Gynaeco-Obstetric and Paediatric Hospital of the City of Yaoundé. HPV genotyping was performed by real-time PCR, HIV serological screening by serial algorithm, CD4 T cell phenotyping by flow cytometry and HIV viral load by Abbott m2000RT. Statistical analyses were performed using Microsoft Excel 2016 and Graph Pad version 6.0 software; with P < 0.05 considered statistically significant. RESULTS: Globally, mean age was 37 ± 3 years; median CD4-count for HIV+ was 414 cells/mm3 [IQR: 264.75-588] and median viremia was 50 RNA copies/mL [IQR: < 40-8288]. Overall HPV rate was 38.49% (107/278); 58.88% for single women vs. others (28.97% married, 2.80% divorced, 9.34% for widows), OR: 2.164; p = 0.0319. Following HIV status, HPV rate was 43.48% (80/184) among HIV+ vs. 28.72% (27/94) among HIV- (OR: 1.937; p < 0.0142); HPV genotypes among HIV+ vs. HIV- were respectively distributed as follows: genotype 16 (3.75% vs. 0.00%, p = 0.57), genotype 18 (3.75% vs. 3.70%, p = 1.00), co-infection 16 and others (8.75% vs. 7.40%, p = 1.00), co-infection 18 and others (8.75% vs. 11.11%, p = 0.71), co-infection 16, 18 and others (2.50% vs. 0.00%, p = 1.00) and other genotypes (72.50% vs. 77.78%, p = 0.80). Among HIV+ participants, HPV rate following CD4 was 62.88% (61/97) for CD4 < 500 vs. 35.71% (20/56) for CD4 ≥ 500 (OR: 3.05; p = 0.0012) while HPV rate following HIV viremia was 42.71% (41/96) with < 1000 RNA copies/ml vs. 66.00% (33/50) with > 1000 RNA copies/ml (OR = 0.384; p = 0.009). CONCLUSION: In Yaoundé, HPV rate appear to be very high, with higher rates of genotypes other than 16 and 18. In the event of HIV infection, the risk of HPV positivity is two times higher, favoured essentially by immunodeficiency. Thus, HIV-infected women should be closely monitored to prevent the emergence of cervical cancer.

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.

Microbiological quality of water sources in the West region of Cameroon: quantitative detection of total coliforms using Micro Biological Survey method.

BACKGROUND: Adequate supply of safe drinking-water remains a critical issue in most developing countries. The whole western region of Cameroon doesn't have a sustainable continuous water supply system, which leads most people to use potentially contaminated water sources to meet their daily water needs. Previous, studies carried out in similar areas of Cameroon have highlighted the poor bacteriological quality of water sources used as drinking-water by the local populations. METHODS: This study used the Micro Biological Survey method, a rapid colorimetric test for the quantitative detection of Coliforms in water samples. 22 water sources (12 improved and 10 unimproved) were identified; 1 water sample of 50 ml was collected in sterile plastic tubes, immediately kept in a refrigerator box and transported to the laboratory for analysis. 1 ml of each sample was inoculated in the Coliforms Micro Biological Survey (Coli MBS) vials initially rehydrated with 10 ml of sterile distilled water. The Coli MBS vials were closed, shaken for about 30 s for homogenization and then incubated at 37 °C. From the initial red color of the Coli MBS vials, changes in color of the reaction vials were monitored at three different time intervals (12 h, 19 h and 24 h), corresponding to three levels of contamination. RESULTS: The average distance (8.7 m) of the latrines from the nearest water source was less than the minimal recommended distance (15 m) to ovoid external contamination. The pH of water samples ranged from 5.5 to 8.3 and the maximum temperature found (26 °C) was almost at level favorable to outbreaks of waterborne diseases such as cholera. The presence of Total Coliforms was detected in 90.91% of the samples. 40% of samples were positive 12 h after the analysis beginning. High level of contamination was observed in unimproved water sources, 50% after 12 h corresponding to Total Coliforms concentration of 10 < x < 103 CFU/ml and the other samples after 19 h (Total Coliforms concentration: 1 < x < 10 CFU/ml). CONCLUSION: This study revealed the poor microbiological quality of water used by local populations of our study sites. There is need to conduct further qualitative microbiology studies to isolate potential germs involved in outcome of diarrheal diseases.

Knowledge and Attitudes of Population Living in Rural and Semi-Rural Areas towards Covid-19 :Case of the Menoua Division, Cameroon.

BACKGROUND: The pandemic situation the world is facing caused by the new SARS-Cov-2 continues to evolve and still represent a real problem. With more than eight thousand reported cases infection, Cameroon stands as the seventh most affected country in Africa. Prevention remains the best way to fight against this zoonosis. However, the limited information available about this infection is a great barrier to stopping the propagation of the virus within the population, especially in rural and semi-rural areas, where the lack of financial and material resources is a reality. This study aimed to assessing Awareness and attitudes of the population of the Menoua Division on COVID-19 infection. METHODS: A cross-sectional study was conducted from March 9 to April 15 2020 amongst the populations of rural and semi-rural areas of the Menoua Division. Data were collected using a questionnaire administered face to face to each participant. The analysis was carried out using the Statistical Analysis System software (SAS version 9.4). The significance threshold was set at a P value of less than 0.05. RESULTS: A total of 434 participants of which male majority (sex ratio 1.07) were included in this study. The most represented age group was [21 - 40] years old representing 40.29% of the participants. Approximately all participants (98.57%) were aware of the world emergency state due to Coronavirus. 75.56%, 91% and 90.93% of the participants knew respectively that having close contacts, kissing and touching the face with the hands could favor the transmission of the virus. However, nearly 91.14% were not aware of the clinical symptoms of the disease. Moreover, 85.02% responded that they would not be able to comply with the confinement measures if they were applied at national level. The level of awareness varied significantly according to the occupation (p=0.038) and the educational level (p<0.001)of the participants. CONCLUSION: The average level of awareness of the population of the Menoua Division on COVID-19 infection was relatively low. Overcoming this pandemic disease means ensuring the flow of the correct information towards the population. Community outreach activities focus on clinical manifestations and what to do in case of COVID-19 infection as well as material and financial support should be help the population to protect themselves effectively against pandemic, particularly in rural areas and surrounding.

The Ebola virus disease outbreak in Tonkolili district, Sierra Leone: a retrospective analysis of the Viral Haemorrhagic Fever surveillance system, July 2014-June 2015.

In Sierra Leone, the Ebola virus disease (EVD) outbreak occurred with substantial differences between districts with someone even not affected. To monitor the epidemic, a community event-based surveillance system was set up, collecting data into the Viral Haemorrhagic Fever (VHF) database. We analysed the VHF database of Tonkolili district to describe the epidemiology of the EVD outbreak during July 2014-June 2015 (data availability). Multivariable analysis was used to identify risk factors for EVD, fatal EVD and barriers to healthcare access, by comparing EVD-positive vs. EVD-negative cases. Key-performance indicators for EVD response were also measured. Overall, 454 EVD-positive cases were reported. At multivariable analysis, the odds of EVD was higher among those reporting contacts with an EVD-positive/suspected case (odds ratio (OR) 2.47; 95% confidence interval (CI) 2.44-2.50; P < 0.01) and those attending funeral (OR 1.02; 95% CI 1.01-1.04; P < 0.01). EVD cases from Kunike chiefdom had a lower odds of death (OR 0.22; 95% CI 0.08-0.44; P < 0.01) and were also more likely to be hospitalised (OR 2.34; 95% CI 1.23-4.57; P < 0.05). Only 25.1% of alerts were generated within 1 day from symptom onset. EVD preparedness and response plans for Tonkolili should include social-mobilisation activities targeting Ebola/knowledge-attitudes-practice during funeral attendance, to avoid contact with suspected cases and to increase awareness on EVD symptoms, in order to reduce delays between symptom onset to alert generation and consequently improve the outbreak-response promptness.

HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon.

BACKGROUND: With the phase-out of stavudine (d4T), change to first-line regimens with zidovudine (AZT) or tenofovir (TDF) in resource-limited settings (RLS) might increase risks of cross-resistance to nucleos(t) ide reverse transcriptase inhibitors (NRTI). This would restrict the scope of switching to the World Health Organisation (WHO)-recommended standard second-line combinations (SLC) without HIV drug resistance (HIVDR)-testing in routine clinical practice. METHODS: An observational study was conducted among 101 Cameroonian patients (55.4% male, median [IQR] age 34 [10-41] years) failing first-line antiretroviral therapy (ART) in 2016, and stratified into three groups according to NRTIs exposure: exposure to both thymidine analogues AZT "and" D4T (group-A, n = 55); exposure to both TDF and AZT "or" D4T (group-B, n = 22); exposure solely to D4T (group-C, n = 24). Protease-reverse transcriptase HIVDR was interpreted using the HIVdb penalty scores (≥60: high-resistance; 20-59: intermediate-resistance; < 20: susceptible). The acceptable threshold for potential-efficacy was set at 80%. RESULTS: The median [IQR] CD4, viral RNA, and time on ART, were respectively 129 [29-466] cells/µl, 71,630 [19,041-368,000] copies/ml, and 4 [2-5] years. Overall HIVDR-level was 89.11% (90/101), with 83.2% harbouring M184 V (high-level 3TC/FTC-resistance) and only 1.98% (2/101) major HIVDR-mutations to ritonavir-boosted protease-inhibitors (PI/r). Thymidine-analogue mutations (TAMs)-1 [T215FY (46.53%), M41 L (22.77%), L210 W (8.91%)], with cross-resistance to AZT and TDF, were higher compared to TAMs-2 [D67N (21.78%), K70R (19.80%), K219QE (18.81%)]. As expected, K65R was related with TDF-exposure: 0% (0/55) in group-A, 22.72% (5/22) group-B, 4.17% (1/24) group-C (p = 0.0013). The potential-efficacy of AZT vs. TDF was respectively 43.64% (24/55) vs. 70.91% (39/55) in group-A (p = 0.0038); 63.64% (14/22) vs. 68.28% (15/22) in group-B (p = 1.0000); and 37.50% (9/24) vs. 83.33% (20/24) in group-C (p = 0.0032). CRF02_AG was the prevailing subtype (63.40%), followed by CRF11.cpx (8.91%), A1 (7.92%), G (5.94%); without any significant effect of the subtype-distribution on HIVDR (92.2% in CRF02_AG vs. 83.8% in non-AG; p = 0.204). CONCLUSION: First-line ART-failure exhibits high-level NRTI-resistance, with potential lower-efficacy of AZT compared to TDF. Significantly, using our 80% efficacy-threshold, only patients without NRTI-substitution on first-line could effectively switch to SLC following the WHO-approach. Patients with multiple NRTI-substitutions (exposed to both thymidine-analogues and TDF) on first-line ART would require HIVDR-testing to select active NRTIs for SLC.

Viral suppression in adults, adolescents and children receiving antiretroviral therapy in Cameroon: adolescents at high risk of virological failure in the era of "test and treat".

BACKGROUND: After the launching of the « Test & Treat ¼ strategy and the wider accessibility to viral load (VL), evaluating virological success (VS) would help in meeting the UNAIDS targets by 2020 in Cameroon. SETTING AND METHODS: Cross-sectional study conducted in the Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management (CIRCB), Yaoundé, Cameroon; data generated between October 2016 and August 2017 amongst adults, adolescents and children at 12, 24, 36 and ≥ 48 months on ART. VS was defined as < 1000 copies/mL of blood plasma and controlled viremia as VL < 50 copies/mL. Data were analysed by SPSS; p < 0.05 considered as significant. RESULTS: 1946 patients (70% female) were enrolled (1800 adults, 105 adolescents, 41 children); 1841 were on NNRTI-based and 105 on PI-based therapy; with 346 patients at M12, 270 at M24, 205 at M36 and 1125 at ≥ M48. The median (IQR) duration on was 48 months (24-48). Overall, VS was 79.4% (95% CI 77.6-81.2) and 67.1% (95% CI 64.9-69.1) had controlled viral replication. On NNRTI-based, VS was 79.9% vs. 71.4% on PIs-based, p = 0.003. By ART duration, VS was 84.1% (M12), 85.9% (M24), 75.1% (M36) and 77.2% (≥ M48), p = 0.001. By age, VS was 75.6% (children), 53.3% (adolescents) and 81.1% (adults), p < 0.001. CONCLUSIONS: In this sub-population of patients receiving ART in Cameroon, about 80% might be experiencing VS, with declining performance at adolescence, with NNRTI-based regimens, and as from 36 months on ART. Thus, improving VS may require an adapted adherence support mechanism, especially for adolescents with long-term treatment in resource-limited settings.

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.

Hepatitis B infection and risk factors among children living with HIV in Yaounde, Cameroon: an integrated management.

BACKGROUND: The endemicity of hepatitis B virus (HBV) prompted the systematic immunization of newborns in Cameroon since 2005. In the frame of a considerable burden of HIV/HBV co-infection (17.5%), monitoring HBV among children living with HIV (CLHIV) would guide toward HIV/HBV integrated paediatric care. We sought to ascertain the prevalence and determinants of HBV infection in the population of CLHIV and performance of commonly used rapid diagnosis tests (RDTs). METHODS: Cross-sectional study conducted from February through June 2017 in a subset of CLHIV ≤15 years old at the Essos Hospital Centre, Yaounde, Cameroon. HBV was tested by HBsAg ELISA sandwich in duplicates for each sample, and the mean optical density was calculated. The Determinants of HBV-prevalencewere evaluated, and p < 0.05 was the significance threshold. The performance of two HBV RDTs (Diaspot vs. HBV-5) was evaluated in comparison to ELISA (used as gold standard). RESULTS: Of the 83 CLHIV enrolled (54.2% female, mean age 8.7 [±3.8] years, 60% vaccinated against HBV, all breastfed), HBV-prevalence was 2.41% (2/83). HBV-positivity was significantly associated with unknown maternal HBV status (2.9% [2/69] vs. 0.0% [0/14], p = 0.0097) and vaginal delivery (2.4% [2/82] vs. 0.0% [0/1], p = 0.0018). Moreover, the most likely to be positive were aged 11 and 15 years, and had experienced neither anti-HBV vaccination nor anti-HBV serum administration, and both had not been treated with any antiseptic solution at birth. Regarding the performance of Diaspot vs. HBV-5 respectively, sensitivity was 100% (2/2) vs. 50% (1/2), while specificity was 100% (45/45) vs. 97.8% (44/45); positive and negative predictive values of Diaspot versus HBV-5 were respectively 100% (2/2) and 100% (45/45) versus 50% (1/2) and 97.8% (44/45). CONCLUSION: HBV-infection in the population of CLHIV appears at a moderate prevalence, suggesting a decreased burden likely due to preventive measures including the wide vaccine coverage. Focusing on mothers with unknown HBV status and promoting safer delivery mode (caesarean section) for HBV-positive motherswould contribute toward pediatric HBV elimination. In context of limited resources, Diaspot test appears more reliable to rollout HBV-infection in the population of CLHIV. As findings are limited to a small sample size, studies on a wider population would be relevant.

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.

The problem of lost to follow-up of mother-child pairs enrolled in the PMTCT program in Dschang District Hospital-Cameroon.

High rates of lost to follow-up (LTFU) in the Prevention of Mother-To-Child Transmission of HIV (PMTCT) programs in Cameroon will only contribute in hindering the successful implementation of the program. The objective of this study was to determine the reasons of LTFU of mother-child pairs enrolled in the PMTCT program in Dschang District Hospital (DDH): Cameroon. Methods: A retrospective cohort study was carried out in HIV+ exposed children delivered in the DDH from1st Jan 2012 - 31st Dec 2014, who were greater than or equal to 18 months at the study period (1st August - 30th September 2016) and whose mothers were enrolled in the PMTCT program for at least 3 months. Children were considered LTFU if they did not return to the hospital for the establishment of their HIV status at 18 months. A complementary cross-sectional study was done whereby a structured questionnaire was administered to the LTFU group via telephone calls, in order to determine the causes of LTFU. Data was collected from hospital registers and analyses done using Epi info 7.1.3.3 software. Results: A total of 141 mother-child pairs were eligible for the study, 76 were reachable via phone calls and 36 (47.37%) met the case definition of LTFU. Out of the 36 (47.37%) children LTFU, lack of information, 19(65.52%); lack of support from male partners, 4(11.11%); Poor behavior of health personnel, 2 (5.56%); forgetfulness, negligence/time wasting, unavailability of results, fear of child being infected, and family problems were all listed at equal proportions of, 3(6.90%) as well as financial problem, 1 (2.78%) were all causes of LTFU identified in this study.

Multimethod Longitudinal HIV Drug Resistance Analysis in Antiretroviral-Therapy-Naive Patients.

The global intensification of antiretroviral therapy (ART) can lead to increased rates of HIV drug resistance (HIVDR) mutations in treated and also in ART-naive patients. ART-naive HIV-1-infected patients from Cameroon were subjected to a multimethod HIVDR analysis using amplification-refractory mutation system (ARMS)-PCR, Sanger sequencing, and longitudinal next-generation sequencing (NGS) to determine their profiles for the mutations K103N, Y181C, K65R, M184V, and T215F/Y. We processed 66 ART-naive HIV-1-positive patients with highly diverse subtypes that underlined the predominance of CRF02_AG and the increasing rate of F2 and other recombinant forms in Cameroon. We compared three resistance testing methods for 5 major mutation sites. Using Sanger sequencing, the overall prevalence of HIVDR mutations was 7.6% (5/66) and included all studied mutations except K65R. Comparing ARMS-PCR with Sanger sequencing as a reference, we obtained a sensitivity of 100% (5/5) and a specificity of 95% (58/61), caused by three false-positive calls with ARMS-PCR. For 32/66 samples, we obtained NGS data and we observed two additional mismatches made up of minority variants (7% and 18%) that might not be clinically relevant. Longitudinal NGS analyses revealed changes in HIVDR mutations in all five positive subjects that could not be attributed to treatment. In one of these cases, superinfection led to the temporary masking of a resistant virus. HIVDR mutations can be sensitively detected by ARMS-PCR and sequencing methods with comparable performances. Longitudinal changes in HIVDR mutations have to be considered even in the absence of treatment.

[The burden of disability in Cameroon]. / Il peso della disabilità in Camerun.

AIM: Rehabilitation services for disabled persons are lacking in countries with limited economic resources. Reliable and objective data are needed to plan for their implementation and to determine the burden of disability in these countries. METHODS: A descriptive cross-sectional study conducted in June 2013 among people living in Dschang Health District, in the West region of Cameroon, to collect information about socio-demographic aspects of physically disabled subjects and health determinants of disabilities. Data was collected using a standard questionnaire in French. RESULTS: In total, 159 physically disabled subjects were enrolled in the study. Mean age was 36 years [± SD 17.26], 55.9% of subjects were female, and 33.8% had a low educational-level. The most frequently reported disabilities were orthopaedic problems (mainly fractures) [45.8%], infectious diseases [29.1%]), and neurological disabilities (mainly hemiplegia [33.3%], hemiparesis [23.8%], and monoplegia [23.8%]). The main causes of disability were trauma due to traffic accidents (17.8%) and inappropriate medical interventions (14.5%). Disability was related to age and 50% of participants experienced social discrimination. Disabled subjects with low-incomes (from 50.000 to 200.000 XAF) were required to pay for rehabilitative care (XAF 10.000 to 100.000), and up to 83% had appealed for improved quality of Rehabilitation Medicine. CONCLUSION: Although Law n. 83/013 for the protection of persons with disabilities in Cameroon dates back to 1983, the results of this study show that disabled people, and children in particular, are still marginalized, vulnerable and have little chance of recovery. Therefore, there is a clear need to improve the quality and availability of rehabilitative care services , with programmatic interventions that ensure implementation of existing laws, improve access to rehabilitative services, provide disabled persons with the necessary specialty medical products, and eliminate barriers to their social participation.

Predictors of poor retention on antiretroviral therapy as a major HIV drug resistance early warning indicator in Cameroon: results from a nationwide systematic random sampling.

BACKGROUND: Retention on lifelong antiretroviral therapy (ART) is essential in sustaining treatment success while preventing HIV drug resistance (HIVDR), especially in resource-limited settings (RLS). In an era of rising numbers of patients on ART, mastering patients in care is becoming more strategic for programmatic interventions. Due to lapses and uncertainty with the current WHO sampling approach in Cameroon, we thus aimed to ascertain the national performance of, and determinants in, retention on ART at 12 months. METHODS: Using a systematic random sampling, a survey was conducted in the ten regions (56 sites) of Cameroon, within the "reporting period" of October 2013-November 2014, enrolling 5005 eligible adults and children. Performance in retention on ART at 12 months was interpreted following the definition of HIVDR early warning indicator: excellent (>85%), fair (85-75%), poor (<75); and factors with p-value < 0.01 were considered statistically significant. RESULTS: Majority (74.4%) of patients were in urban settings, and 50.9% were managed in reference treatment centres. Nationwide, retention on ART at 12 months was 60.4% (2023/3349); only six sites and one region achieved acceptable performances. Retention performance varied in reference treatment centres (54.2%) vs. management units (66.8%), p < 0.0001; male (57.1%) vs. women (62.0%), p = 0.007; and with WHO clinical stage I (63.3%) vs. other stages (55.6%), p = 0.007; but neither for age (adults [60.3%] vs. children [58.8%], p = 0.730) nor for immune status (CD4351-500 [65.9%] vs. other CD4-staging [59.86%], p = 0.077). CONCLUSIONS: Poor retention in care, within 12 months of ART initiation, urges active search for lost-to-follow-up targeting preferentially male and symptomatic patients, especially within reference ART clinics. Such sampling strategy could be further strengthened for informed ART monitoring and HIVDR prevention perspectives.