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30 result(s) for "Aghokeng, Avelin F."
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Viral load suppression in HIV-infected adolescents in cameroon: towards achieving the UNAIDS 95% viral suppression target
Background Achieving the UNAIDS 95% sustained viral suppression (VS) rate requires considerable global efforts, particularly among adolescents living with HIV (ALHIV) who are often associated with high rates of virological failure (VF). In this study, we prospectively assessed the rate of VS, and the factors associated with VF in a cohort of adolescents followed up according to the WHO guidelines in Cameroon. Methods A cross-sectional study was carried out in 2021 among adolescents (aged 10–19 years) receiving ART in the national program in Cameroon. Socio-demographic and clinical data were collected using patients’ medical files and a brief interview with the participant and/or his guardian. Thereafter, a first viral load test (VL1) was performed using the ABBOTT Platform. For adolescents with VL1 > 1000 copies/ml, adherence-enhancing interventions were routinely performed each month for 3 consecutive months, after which a second viral load (VL2) was measured. Adolescents with VL2 > 1000 copies/ml were considered in VF. Results Overall, 280 adolescents were enrolled, of whom 89.3% (250/280) acquired HIV infection via mother-to-child transmission. The median age was 16.0 (IQR: 13.0–18.0) years and the median duration on ART was 9.8 (IQR: 5.1–12.8) years. Females and males were almost equally represented, as 52.1% (146/280) were female, while 47.9% (134/280) were males (p = 0.47). The VS rate was 88.2% (CI: 83.8-91.7%) overall; 89.0% (CI: 82.0-93.1%) and 88.7% (CI: 81.2-93.0%) in females and males, respectively. Being on second or third-line ART, self-declared suboptimal adherence, and a history of past VF were independently associated with VF. Conclusion The high rate of VS we report in this study is welcome in the era of the 95/95/95 UNAIDS goals, and indicates that improving treatment outcomes in this specific and fragile population that represent adolescents in Sub-Saharan Africa is achievable. Trial registration 20/10/2020 NCT04593979 ( https://clinicaltrials.gov/ct2/show/NCT04593979 ).
HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing
The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naïve individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naïve individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy.
Prevalence and Genetic Diversity of Bat Hepatitis B Viruses in Bat Species Living in Gabon
Hepatitis B virus (HBV) infection leads to around 800,000 deaths yearly and is considered to be a major public health problem worldwide. However, HBV origins remain poorly understood. Here, we looked for bat HBV (BtHBV) in different bat species in Gabon to investigate the role of these animals as carriers of ancestral hepadnaviruses because these viruses are much more diverse in bats than in other host species. DNA was extracted from 859 bat livers belonging to 11 species collected in caves and villages in the southeast of Gabon and analyzed using PCRs targeting the surface gene. Positive samples were sequenced using the Sanger method. BtHBV DNA was detected in 64 (7.4%) individuals belonging to eight species mainly collected in caves. Thirty-six (36) sequences among the 37 obtained after sequencing were phylogenetically close to the RBHBV strain recently isolated in Gabonese bats, while the remaining sequence was close to a rodent HBV strain isolated in America. The generalized linear mixed model showed that the variable species best explained the occurrence of BtHBV infection in bats. The discovery of a BtHBV strain homologous to a rodent strain in bats raises the possibility that these animals may be carriers of ancestral hepadnaviruses.
Inaccurate Diagnosis of HIV-1 Group M and O Is a Key Challenge for Ongoing Universal Access to Antiretroviral Treatment and HIV Prevention in Cameroon
Increased access to HIV testing is essential in working towards universal access to HIV prevention and treatment in resource-limited countries. We here evaluated currently used HIV diagnostic tests and algorithms in Cameroon for their ability to correctly identify HIV infections. We estimated sensitivity, specificity, and positive and negative predictive values of 5 rapid/simple tests, of which 3 were used by the national program, and 2 fourth generation ELISAs. The reference panel included 500 locally collected samples; 187 HIV -1 M, 10 HIV-1 O, 259 HIV negative and 44 HIV indeterminate plasmas. None of the 5 rapid assays and only 1 ELISA reached the current WHO/UNAIDS recommendations on performance of HIV tests of at least 99% sensitivity and 98% specificity. Overall, sensitivities ranged between 94.1% and 100%, while specificities were 88.0% to 98.8%. The combination of all assays generated up to 9% of samples with indeterminate HIV status, because they reacted discordantly with at least one of the different tests. Including HIV indeterminate samples in test efficiency calculations significantly decreased specificities to a range from 77.9% to 98.0%. Finally, two rapid assays failed to detect all HIV-1 group O variants tested, with one rapid test detecting only 2 out of 10 group O specimens. In the era of ART scaling-up in Africa, significant proportions of false positive but also false negative results are still observed with HIV screening tests commonly used in Africa, resulting in inadequate treatment and prevention strategies. Depending on tests or algorithms used, up to 6% of HIV-1 M and 80% of HIV-1 O infected patients in Cameroon do not receive ART and adequate counseling to prevent further transmission due to low sensitivities. Also, the use of tests with low specificities could imply inclusion of up to 12% HIV negative people in ART programs and increase budgets in addition to inconveniences caused to patients.
Population-Based Monitoring of Emerging HIV-1 Drug Resistance on Antiretroviral Therapy and Associated Factors in a Sentinel Site in Cameroon: Low Levels of Resistance but Poor Programmatic Performance
Scale-up of antiretroviral therapy (ART) in resource-limited settings has drastically reduced HIV-related morbidity and mortality. However, challenges in long-term ART, adherence and HIV drug resistance (HIVDR) itself, require monitoring to limit HIVDR emergence among ART-experienced populations, in order to ensure regimen efficacy. A longitudinal study was conducted from 2009-2011 in a cohort of 141 HIV-infected adult patients (aged >21) at the national social insurance centre hospital in Yaounde, Cameroon. As per-WHO HIVDR protocol, HIV-1 protease-reverse transcriptase genotyping was performed at baseline and at endpoint (12 months) on first-line ART using ViroSeq™ Genotyping kit. At baseline, a prevalence of 3.6% (5/139) HIVDR was observed [protease inhibitors M46I (1/5), G73A (1/5), L90LM (1/5); nucleoside reverse transcriptase inhibitors: M184V (1/5), T215F (1/5); non-nucleoside reverse transcriptase inhibitors: K103N (1/5), Y181Y/C (2/5), M230ML (1/5)]. At endpoint, 54.0% (76) patients were followed-up, 9.2% (13) died, and 3.5% (5) transferred, 38.5% (47) lost to follow-up (LTFU). 69.7% (53/76) of those followed-up had viremia <40 copies/ml and 90.8% (69/76) <1000 copies/ml. 4/7 patients with viremia ≥1000 copies/ml harbored HIVDR (prevalence: 5.3%; 4/76), with M184V/I (4/4) and K103K/N (3/4) being the most prevalent mutations. LTFU was favored by costs for consultation/laboratory tests, drug shortages, workload (physician/patient ratio: 1/180) and community disengagement. Low levels of HIVDR at baseline and at endpoint suggest a probable effectiveness of ART regimens used in Cameroon. However the possible high rate of HIVDR among LTFUs limited the strengths of our findings. Evaluating HIVDR among LTFU, improving adherence, task shifting, subsidizing/harmonizing costs for routine follow-up, are urgent measures to ensure an improved success of the country ART performance.
Early Warning Indicators for HIV Drug Resistance in Cameroon during the Year 2010
Rapid scale-up of antiretroviral therapy (ART) in resource-limited settings is accompanied with an increasing risk of HIV drug resistance (HIVDR), which in turn could compromise the performance of national ART rollout programme. In order to sustain the effectiveness of ART in a resource-limited country like Cameroon, HIVDR early warning indicators (EWI) may provide relevant corrective measures to support the control and therapeutic management of AIDS. A retrospective study was conducted in 2010 among 40 ART sites (12 Approved Treatment Centers and 28 Management Units) distributed over the 10 regions of Cameroon. Five standardized EWIs were selected for the evaluation using data from January through December, among which: (1) Good ARV prescribing practices: target = 100%; (2) Patient lost to follow-up: target ≤ 20%; (3) Patient retention on first line ART: target ≥ 70%; (4) On-time drug pick-up: target ≥ 90%; (5) ARV drug supply continuity: target = 100%. Analysis was performed using a Data Quality Assessment tool, following WHO protocol. THE NUMBER OF SITES ATTAINING THE REQUIRED PERFORMANCE ARE: 90% (36/40) for EWI(1), 20% (8/40) for EWI(2); 20% (8/40) for EWI(3); 0% (0/37) for EWI(4); and 45% (17/38) for EWI 5. ARV prescribing practices were in conformity with the national guidelines in almost all the sites, whereas patient adherence to ART (EWI(2), EWI(3), and EWI(4)) was very low. A high rate of patients was lost-to-follow-up and others failing first line ART before 12 months of initiation. Discontinuity in drug supply observed in about half of the sites may negatively impact ARV prescription and patient adherence. These poor ART performances may also be due to low number of trained staff and community disengagement. The poor performance of the national ART programme, due to patient non-adherence and drug stock outs, requires corrective measures to limit risks of HIVDR emergence in Cameroon.
Characterization of a new simian immunodeficiency virus strain in a naturally infected Pan troglodytes troglodytes chimpanzee with AIDS related symptoms
Data on the evolution of natural SIV infection in chimpanzees (SIVcpz) and on the impact of SIV on local ape populations are only available for Eastern African chimpanzee subspecies (Pan troglodytes schweinfurthii), and no data exist for Central chimpanzees (Pan troglodytes troglodytes), the natural reservoir of the ancestors of HIV-1 in humans. Here, we report a case of naturally-acquired SIVcpz infection in a P.t.troglodytes chimpanzee with clinical and biological data and analysis of viral evolution over the course of infection. A male chimpanzee (Cam155), 1.5 years, was seized in southern Cameroon in November 2003 and screened SIV positive during quarantine. Clinical follow-up and biological analyses have been performed for 7 years and showed a significant decline of CD4 counts (1,380 cells/mm³ in 2004 vs 287 in 2009), a severe thrombocytopenia (130,000 cells/mm³ in 2004 vs 5,000 cells/mm³ in 2009), a weight loss of 21.8% from August 2009 to January 2010 (16 to 12.5 kg) and frequent periods of infections with diverse pathogens.DNA from PBMC, leftover from clinical follow-up samples collected in 2004 and 2009, was used to amplify overlapping fragments and sequence two full-length SIVcpzPtt-Cam155 genomes. SIVcpzPtt-Cam155 was phylogenetically related to other SIVcpzPtt from Cameroon (SIVcpzPtt-Cam13) and Gabon (SIVcpzPtt-Gab1). Ten molecular clones 5 years apart, spanning the V1V4 gp120 env region (1,100 bp), were obtained. Analyses of the env region showed positive selection (dN-dS >0), intra-host length variation and extensive amino acid diversity between clones, greater in 2009. Over 5 years, N-glycosylation site frequency significantly increased (p < 0.0001). Here, we describe for the first time the clinical history and viral evolution of a naturally SIV infected P.t.troglodytes chimpanzee. The findings show an increasing viral diversity over time and suggest clinical progression to an AIDS-like disease, showing that SIVcpz can be pathogenic in its host, as previously described in P.t.schweinfurthii. Although studying the impact of SIV infection in wild apes is difficult, efforts should be made to better characterize the pathogenicity of the ancestors of HIV-1 in their natural host and to find out whether SIV infection also plays a role in ape population decline.
Extraordinary Heterogeneity of Virological Outcomes in Patients Receiving Highly Antiretroviral Therapy and Monitored With the World Health Organization Public Health Approach in Sub-Saharan Africa and Southeast Asia
Background. The limited access to virological monitoring in developing countries is a major weakness of the current antiretroviral treatment (ART) strategy in these settings. We conducted a large cross-sectional study in Burkina Faso, Cameroon, Cote d'Ivoire, Senegal, Togo, Thailand, and Vietnam to assess virological failure and drug resistance mutations (DRMs) after 12 or 24 months of ART. Methods. Between 2009 and 2011, we recruited adults attending ART centers 10–14 months (the M12 group) or 22–26 months (M24 group) after initiating ART. Demographic and clinical data were collected on site, and viral load was measured. Samples with a viral load of ≥ 1000 copies/mL, considered as the failure threshold, were genotyped for drug resistance assessment. Results. Overall, 3935 patients were recruited (2060 at M12 and 1875 at M24). Median ages varied from 32 to 42 years. Median CD4 + T-cell counts at ART initiation were low (99–172 cells/μL). The main ART regimens included stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. Overall, virological failure frequency was 11.1% for M12 patients and 12.4% for M24 patients, and 71.0% to 86.1% of these patients, respectively, had drug-resistant virus. Across sites, virological failure varied from 2.9% to 20.6% in M12 patients and from 3.7% to 26.0% in M24 patients. Predominant DRMs were associated with ART regimens, but virus in several patients accumulated DRMs to drugs not received, such as abacavir, didanosine, tenofovir, etravirine, and rilpivirine. Conclusions. Our findings show heterogeneous virological failure and illustrate that, in addition to routine access to viral load, good management of ART programs is even more critical to improve treatment outcomes in resource-limited countries.
Declining trends in early warning indicators for HIV drug resistance in Cameroon from 2008–2010: lessons and challenges for low-resource settings
Background Rapid scale-up of antiretroviral therapy (ART) and limited access to genotyping assays in low-resource settings (LRS) are inevitably accompanied by an increasing risk of HIV drug resistance (HIVDR). The current study aims to evaluate early warning indicators (EWI) as an efficient strategy to limit the development and spread of preventable HIVDR in these settings, in order to sustain the performance of national antiretroviral therapy (ART) rollout programmes. Methods Surveys were conducted in 2008, 2009 and 2010 within 10 Cameroonian ART clinics, based on five HIVDR EWIs: (1) Good prescribing practices; (2) Patient lost to follow-up; (3) Patient retention on first line ART; (4) On-time drug pick-up; (5) Continuous drug supply. Analysis was performed as per the World Health Organisation (WHO) protocol. Results An overall decreasing performance of the national ART programme was observed from 2008 to 2010: EWI 1 (100% to 70%); EWI 2 (40% to 20%); EWI 3 (70% to 0%); EWI 4 (0% throughout); EWI 5 (90% to 40%). Thus, prescribing practices (EWI 1 ) were in conformity with national guidelines, while patient adherence (EWI 2 , EWI 3 , and EWI 4 ) and drug supply (EWI 5 ) were lower overtime; with a heavy workload (median ratio ≈1/64 staff/patients) and community disengagement observed all over the study sites. Conclusions In order to limit risks of HIVDR emergence in poor settings like Cameroon, continuous drug supply, community empowerment to support adherence, and probably a reduction in workload by task shifting, are the potential urgent measures to be undertaken. Such evidence-based interventions, rapidly generated and less costly, would be relevant in limiting the spread of preventable HIVDR and in sustaining the performance of ART programmes in LRS.
Virological outcome and patterns of HIV‐1 drug resistance in patients with 36 months’ antiretroviral therapy experience in Cameroon
Introduction The current expansion of antiretroviral treatment (ART) in the developing world without routine virological monitoring still raises concerns on the outcome of the strategy in terms of virological success and drug resistance burden. We assessed the virological outcome and drug resistance mutations in patients with 36 months’ ART experience, and monitored according to the WHO public health approach in Cameroon. Methods We consecutively recruited between 2008 and 2009 patients attending a national reference clinic in Yaoundé – Cameroon, for their routine medical visits at month 36±2. Observance data and treatment histories were extracted from medical records. Blood samples were collected for viral load (VL) testing and genotyping of drug resistance when HIV‐1 RNA≥1000 copies/ml. Results Overall, 376 HIV‐1 infected adults were recruited during the study period. All, but four who received PMTCT, were ART‐naïve at treatment initiation, and 371/376 (98.7%) started on a first‐line regimen that included 3TC +d4T/AZT+NVP/EFV. Sixty‐six (17.6%) patients experienced virological failure (VL≥1000 copies/ml) and 53 carried a resistant virus, thus representing 81.5% (53/65) of the patients who failed. Forty‐two out of 53 were resistant to nucleoside and non‐nucleoside reverse‐transcriptase inhibitors (NRTIs+NNRTIs), one to protease inhibitors (PI) and NNRTIs, two to NRTIs only and eight to NNRTIs only. Among patients with NRTI resistance, 18/44 (40.9%) carried Thymidine Analog Mutations (TAMs), and 13/44 (29.5%) accumulated at least three NRTI resistance mutations. Observed NNRTI resistance mutations affected drugs of the regimen, essentially nevirapine and efavirenz, but several patients (10/51, 19.6%) accumulated mutations that may have compromised etravirine use. Conclusions We observed a moderate level of virological failure after 36 months of treatment, but a high proportion of patients who failed developed drug resistance. Although we found that for the majority of patients, second‐line regimens recommended in Cameroon would be still effective, accumulated resistance mutations are of concern and may compromise future treatment strategies, stressing the need for virological monitoring in resource‐limited settings.