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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.

Abstract Background 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. Results 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). Conclusions 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.

Abstract 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 ).

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. [ABSTRACT FROM AUTHOR]

Objectives Integrase strand transfer inhibitors (INSTIs) have been recently recommended as the preferred first-line option for antiretroviral treatment initiators in low- and middle-income countries (LMICs) in response to the growing circulation of resistant HIV to non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this study, we estimated the frequency of pretreatment drug resistance (PDR) to INSTIs in West Africa and Southeast Asia. Materials and methods Using samples collected from 2015 to 2016, and previously used to assessed PI, NRTI and NNRTI resistance, we generated HIV integrase sequences and identified relevant INSTI PDR mutations using the Stanford and ANRS algorithms. Results We generated 353 integrase sequences. INSTI PDR frequency was low, 1.1% (4/353) overall, ranging from 0% to 6.3% according to country. However, frequency of PDR to any drug class was very high, 17.9% (95% CI: 13.9%–22.3%), and mostly associated with a high level of NNRTI PDR, 9.7%, and a moderate level of NRTI PDR, 5.3%. Conclusions Our results support the recent introduction of INSTIs in LMICs to improve treatment outcome in these settings, but also stress the need for effective actions to prevent uncontrolled emergence of drug resistance to this drug class. [ABSTRACT FROM AUTHOR]

IntroductionHuman T-cell lymphotrophic virus type-1 (HTLV-1) and human immunodeficiency virus (HIV-1) co-infection occur in many populations. People living with HIV-1 and infected with HTLV-1 seem more likely to progress rapidly towards AIDS. Both HTLV-1 and HIV-1 are endemic in Gabon (Central Africa). We investigated HTLV-1 and HIV-1 co-infection in the Haut-Ogooué province, and assessed factors that may favor the rapid evolution and progression to AIDS in co-infected patients.MethodsPlasma samples from HTLV-1 patients were tested using ELISA, and positive samples were then tested by western blot assay (WB). We used the polymerase chain reaction to detect HTLV-1 Tax/Rex genes using DNA extracted from the buffy coat of ELISA-positives samples.ResultsWe recruited 299 individuals (mean age 46 years) including 90 (30%) men and 209 (70%) women, all of whom are under treatment at the Ambulatory Treatment Centre of the province. Of these, 45 were ELISA HTLV-1/2 seropositive. According to WB criteria, 21 of 45 were confirmed positive: 20 were HTLV-1 (44%), 1 was HTLV-1/2 (2%), 2 were indeterminate (4%) and 22 were seronegative (49%). PCR results showed that 23 individuals were positive for the Tax/Rex region. Considering both serological and molecular assays, the prevalence of HTLV-1 infection was estimated at 7.7%. Being a woman and increasing age were found to be independent risk factors for co-infection. Mean CD4+ cell counts were higher in HTLV-1/HIV-1 co-infected (578.1 (± 340.8) cells/mm3) than in HIV-1 mono-infected (481.0 (± 299.0) cells/mm3) Individuals. Similarly, the mean HIV-1 viral load was Log 3.0 (± 1.6) copies/ml in mono-infected and Log 2.3 (± 0.7) copies/ml in coinfected individuals.ConclusionWe described an overall high prevalence of HTLV-1/HIV-1 co-infection in Gabon. Our findings stress the need of strategies to prevent and manage these co-infections.

The objective of this study was to determine the rates of virological failure (VF) and HIV drug resistance (HIVDR) amongst adolescents on antiretroviral Therapy (ART). A retrospectively designed study was conducted in 10 healthcare centers for adolescents living with HIV (ALHIV) in the two main cities of Cameroon (Yaoundé and Douala), from November 2018 to May 2019. Sociodemographic, clinical, therapeutic and laboratory parameters were collected from medical records. All enrolled ALHIV had viral load (VL) measurements following the national guidelines. All patients with a VL ≥ 1000 copies/ml were called to perform genotyping tests. The chi-square test was used to determine the factors associated with VF. Out of the 1316 medical records of ALHIV, we included 1083 ALHIV having a VL result. Among them, 276 (25.5%) were experiencing VF, and VF was significantly higher in ALHIV with suboptimal adherence (p

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.

Background: Population-based studies to estimate viral load (VL) suppression and rate of acquired HIV drug resistance (ADR) are essential in sub-Saharan Africa. We conducted the first nationally representative study estimating VL suppression and ADR in Cameroon. Methods: Eligible participants were patients on antiretroviral therapy (ART) for 12 to 24 months (ART 12–24) or 48 to 60 months (ART 48–60). ART 12–24 participants were recruited from 24 randomly selected clinics in both urban and rural regions. ART 48–60 participants were recruited from 7 urban clinics. Recruitment occurred from February to August 2015. Dried blood spots (DBSs) and plasma specimens were collected and tested for HIV-1 RNA level and presence of drug resistance mutations (DRM) when VL ≥1000 copies/ml. Results: Overall, 1064 ART 12–24 and 388 ART 48–60 participants were recruited. Viral suppression in the ART 12–24 group was 72.1% (95% CI: 66.3–77.2) overall, 75.0% (65.2–82.7) in urban sites, and 67.7% (58.3–75.8) in rural sites. In the ART 48–60 group, viral suppression was 67.7% (55.8–77.7). Overall, HIV drug resistance (HIVDR) was 17.7% (15.1–20.6) and 28.3% (17.4–42.5) in the ART 12–24 and ART 48–60 groups, respectively. However, among patients with VL ≥1000 copies/ml, HIVDR was identified in 63.3% (52.0–73.3) of ART 12–24 patients, and in 87.7% (67.4–96.1) of ART 48–60 patients. Conclusions: Results of this first nationwide study indicate alarming levels of virological failure and ADR in Cameroon. Better ART management is urgently needed and should focus on improving ART adherence, availability of VL monitoring, and more timely switches to second-line ART. Keywords: HIV, Viral load suppression, Drug resistance, Cameroon

Objectives To characterize HIV drug resistance (HIVDR) below and above the WHO threshold of 1000 copies/mL, considered for the definition of HIV ART failure in resource-limited settings. Methods From a cohort of 280 adolescents (aged 10–19 years) receiving ART for at least 6 months, genotypic resistance testing (GRT) was attempted for two groups of participants: participants with low-level viraemia [LLV; viral load (VL) 200–999 copies/mL] and those in virological failure (VF; confirmed VL ≥1000 copies/mL) using an in-house method. The Stanford HIValg Program was used to identify relevant HIVDR mutations and predict the efficacy of the newly introduced tenofovir-lamivudine-dolutegravir combination. Results GRT was successfully performed in 54/58 (93.1%) eligible participants, of which 28/31 (90.3%) were in VF and 26/27 (96.3%) had LLV. A high level of resistance was found both in adolescents with LLV and those in VF, with respectively 84.6% (22/26) and 75.0% (21/28) of participants harbouring at least one HIVDR mutation. NRTIs and NNRTIs were the most affected drug classes in both population groups. In contrast, PIs were not significantly affected and dolutegravir was expected to be active for all participants tested. However, for the newly introduced dolutegravir-based combination, functional monotherapy (dolutegravir only) was potentially possible for 22.7% (5/22) of the participants with LLV. Conclusions Our findings show that the 1000 copies/mL threshold is not an indicator of virological success and we call for a revision of the current WHO definition of VF in resource-limited countries. [ABSTRACT FROM AUTHOR]

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The selected HIV diagnostic assays currently used in Cameroon on a panes of HIV-positive and -negative sera, representing the perdominant viral strains and monitor the impact of mutations within the IDR of the gp41 domain on antibodies detection is studied. The importance of prior test evaluations on local serum panels and in field conditions before a national policy for HIV screening is decided on and stress also the need to use tests and algorithms that can reduce the high number of HIV-indeterminate results in Africa.