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BackgroundAntiretroviral treatment increases the risk of accumulation of resistance mutations that negatively impact the possibilities of future treatment. This study aimed to present the frequency of HIV-1 antiretroviral resistance mutations and the genetic diversity among children with virological failure in five pediatric care facilities in Benin.MethodsA cross-sectional study was carried out from November 20, 2020, to November 30, 2022, in children under 15 years of age who failed ongoing antiretroviral treatment at five facilities care in Benin (VL > 3log10 on two consecutive realizations three months apart). Viral loads were measured using the m2000 RealTime Abbott platform. Genotyping was carried out with the commercial Viroseq kit. Sequences were read on the ABI 3500 sequencer and then edited with ViroSeqHIVv3.0 software. The HIV drug resistance database at Stanford University was used to identify mutations and viral subtypes were assigned by phylogenetic analyses.ResultsThe HIV-1 pol gene was sequenced in 47 participants with virological failure of antiretroviral treatment. The median age was 120 [Interquartile Range 90-144] months. The prevalent treatment was EFV base regimen (22/47; 46.8%). Median viral load was 4.39 log10 [IQR 3.81-4.86 log10] respectively. Resistance testing was successful among (37/47; 78.72%) children, resistance mutations were detected in (32/37; 86.48%) children, and (29/32; 90.62%) had at least one surveillance drug resistance mutation. Respectively (25/32; 78.12%), (28/32; 87.5%), (4/32; 12.90%), (22/32; 68.75%) had at least one resistance mutation associated with NRTIs, NNRTIs, PIs and NNRTIs+NRTIs. (12/32; 37.5%) of children carried mutations related to TAMs. the most frequently NRTIs identified were M184V (21/62; 33.9%) followed by TAMs (20/62; 32.2%) and T69G/D (2/62; 3.2%)s. Among mutations associated with NNRTIs K103N represented (18/64; 28.1%) followed by P225H (7/64; 10.9%). The I54V (3/6; 50%) mutation is the major PI observed. Genetic diversity is characterized by a preponderance of CRF02_AG (72%, 23/32), followed by unique recombinant forms (URFs) (25%, 8/32) and one subtype G.ConclusionA high rate of mutations has been observed in children. These data underline the importance of implementing routine genotypic testing in the biological monitoring of infected children to anticipate the accumulation of resistance mutations and thus compromise the treatment options available in Benin.

BACKGROUND:Vulnerable individuals with tuberculosis (TB) struggle to access and stay on treatment. While patient-related and social barriers to TB treatment adherence are well documented, less is known about how the organisation and delivery of TB care influences adherence behaviour. AIM:To examine the influence of TB service organisation and culture on patients' experience of starting and staying on treatment in Riga, Latvia. METHODS:An intervention package to support adherence to TB treatment amongst vulnerable patients in Riga, Latvia was piloted between August 2016 and March 2017. Qualitative observations (5), interviews with staff (20) and with TB patients (10) were conducted mid-way and at the end of the intervention to understand perceptions, processes, and experiences of TB care. RESULTS:The organisation of TB services is strongly influenced by a divide between medical and social aspects of TB care. Communication and care practices are geared towards addressing individual risk factors for non-adherence rather than the structural vulnerabilities that patients experience in accessing care. Support for vulnerable patients is limited because of standardised programmatic approaches, resource constraints and restricted job descriptions for non-medical staff. CONCLUSION:Providing support for vulnerable patients is challenged in this setting by the strict division between medical and social aspects of TB care, and the organisational focus on patient-related rather than systems-related barriers to access and adherence. Potential systems interventions include the introduction of multi-disciplinary approaches and teams in TB care, strengthening patient literacy at the point of treatment initiation, as well as stronger linkages with social care organisations.

BACKGROUND: Although the outbreak of human immunodeficiency virus type 1 (HIV-1) in Guangdong has been documented for more than a decade, the molecular characteristics of such a regional HIV-1 epidemic remained unknown. METHODOLOGY/PRINCIPAL FINDINGS: By sequencing of HIV-1 pol/env genes and phylogenetic analysis, we performed a molecular epidemiologic study in a representative subset (n = 200) of the 508 HIV-1-seropositive individuals followed up at the center for HIV/AIDS care and treatment of Guangzhou Hospital of Infectious Diseases. Of 157 samples (54.1% heterosexual acquired adults, 20.4% needle-sharing drug users, 5.7% receivers of blood transfusion, 1.3% men who have sex with men, and 18.5% remained unknown) with successful sequencing for both pol and env genes, 105 (66.9%) HIV-1 subtype CRF01_AE and 24 (15.3%) CRF07_BC, 9 (5.7%) B', 5 (3.2%) CRF08_BC, 5 (3.2%) B, 1 (0.6%) C, 3 (1.9%) CRF02_AG, and 5 (3.2%) inter-region recombinants were identified within pol/env sequences. Thirteen (8.3%) samples (3 naïves, 6 and 5 received with antiretroviral treatment [ART] 1-21 weeks and ≥24 weeks respectively) showed mutations conferring resistance to nucleoside/nonnucleoside reverse transcriptase inhibitors or protease inhibitors. Among 63 ART-naïve patients, 3 (4.8%) showed single or multiple drug resistant mutations. Phylogenetic analysis showed 8 small clusters (2-3 sequences/cluster) with only 17 (10.8%) sequences involved. CONCLUSION/SIGNIFICANCE: This study confirms that sexual transmission with dominant CRF01_AE strain is a major risk for current HIV-1 outbreak in the Guangdong's general population. The transmission with drug-resistant variants is starting to emerge in this region.

BACKGROUND: The classification of HIV-1 strains in subtypes and Circulating Recombinant Forms (CRFs) has helped in tracking the course of the HIV pandemic. In Senegal, which is located at the tip of West Africa, CRF02_AG predominates in the general population and Female Sex Workers (FSWs). In contrast, 40% of Men having Sex with Men (MSM) in Senegal are infected with subtype C. In this study we analyzed the geographical origins and introduction dates of HIV-1 C in Senegal in order to better understand the evolutionary history of this subtype, which predominates today in the MSM population METHODOLOGY/PRINCIPAL FINDINGS: We used a combination of phylogenetic analyses and a Bayesian coalescent-based approach, to study the phylogenetic relationships in pol of 56 subtype C isolates from Senegal with 3,025 subtype C strains that were sampled worldwide. Our analysis shows a significantly well supported cluster which contains all subtype C strains that circulate among MSM in Senegal. The MSM cluster and other strains from Senegal are widely dispersed among the different subclusters of African HIV-1 C strains, suggesting multiple introductions of subtype C in Senegal from many different southern and east African countries. More detailed analyses show that HIV-1 C strains from MSM are more closely related to those from southern Africa. The estimated date of the MRCA of subtype C in the MSM population in Senegal is estimated to be in the early 80's. CONCLUSIONS/SIGNIFICANCE: Our evolutionary reconstructions suggest that multiple subtype C viruses with a common ancestor originating in the early 1970s entered Senegal. There was only one efficient spread in the MSM population, which most likely resulted from a single introduction, underlining the importance of high-risk behavior in spread of viruses.