Drug resistance in children and adolescents with HIV in Panama.

OBJECTIVES: The inadequacy of resistance monitoring in Latin America leads to circulation of HIV strains with drug resistance mutations (DRMs), compromising ART effectiveness. This study describes the DRM prevalence in HIV-infected paediatric patients in Panama. METHODS: During 2018-19, plasma was collected from 76 HIV-infected children/adolescents (5 ART-naive, 71 treated) in Panama for HIV-1 DRM pol analysis, predicted antiretroviral (ARV) susceptibility by Stanford, and HIV-1 variant phylogenetic characterization. RESULTS: HIV-1 pol sequences were recovered from 67 (88.2%) of 76 children/adolescents (median age 12 years), carrying 65 subtype B, 1 subtype G and 1 unique recombinant URF_A1B. Five were ART-naive and 62 ART-treated under virological failure (viraemia >50 copies/mL) with previous exposure to NRTIs, (100%), NNRTIs (45.2%), PIs (95.2%) and integrase strand transfer inhibitors (INSTIs, 17.7%). Among the treated patients, 34 (54.8%) carried resistant strains, with major DRMs to one (40.3%), two (9.7%) or three (4.8%) ARV families. Most of them harboured DRMs to NRTIs (58.5%) or NNRTIs (39%), but also major DRMs to PIs (4.9%) and INSTIs (6.5%). We also found dual-class NRTI + NNRTI (12.2%) and NNRTI + PI (2.6%) resistance. Two naive subjects carried viruses with DRMs to NRTIs and NRTI + NNRTI, respectively. Sequenced viruses presented high/intermediate resistance mainly to emtricitabine/lamivudine (48.9% each) and efavirenz/nevirapine (33.3% each). Most participants were susceptible to PIs (91.3%) and INSTIs (88.1%). CONCLUSIONS: The high DRM prevalence to NRTIs and NNRTIs observed among treated HIV-infected children/adolescents in Panama justifies the need for routine resistance monitoring for optimal rescue therapy selection in this vulnerable population.

HIV diagnosis in Equatorial Guinea. Keys to reduce the diagnostic and therapeutic delay.

BACKGROUND: In Equatorial Guinea, only 54 % of people living with HIV know their HIV status. There are no confirmatory or molecular diagnostic techniques for early diagnosis or monitoring of infection in the country. Rapid diagnostic tests can induce false-positive diagnoses if used as a confirmatory technique. Our study aimed to identify the challenges of early HIV diagnosis in Equatorial Guinea by analyzing the rate of false positive diagnoses, diagnostic and therapeutic delays, and treatment failures among those on antiretroviral therapy. METHODS: From 2019-2022, dried blood from 341 children, adolescents and adults diagnosed in Equatorial Guinea as HIV-positive by rapid diagnostic testing, and from 54 HIV-exposed infants were collected in Bata and sent to Madrid to confirm HIV-infection by molecular (Xpert HIV-1Qual, Cepheid) and/or serological confirmatory assays (Geenius-HIV-1/2, BioRad). HIV diagnostic delay (CD4 <350cells/mm3), advanced disease at diagnosis (CD4 <200cells/mm3) and antiretroviral treatment delay and failure (viraemia >1,000RNA-HIV-1-copies/ml) were also studied after viral quantification (XpertVL HIV-1, Cepheid). RESULTS: False-positive diagnoses were identified in 5 % of analysed samples. HIV infection was confirmed in 90.5 % of previously diagnosed patients in Equatorial Guinea and 3.7 % of HIV-exposed children undiagnosed in the field. Two-thirds of each new HIV patient had delayed diagnosis, and one-third had advanced disease. Treatment delay occurred in 28.3 % of patients, being around four times more likely in adolescents/adults than children. More than half (56 %) of 232 treated patients presented treatment failure, being significantly higher in children/adolescents than in adults (82.9 %/90 % vs. 45.6 %, p < 0.001). CONCLUSION: We identified some challenges of early HIV diagnosis in Equatorial Guinea, revealing a high rate of false positive diagnoses, diagnostic/treatment delays, and treatment failures that need to be addressed. The implementation of more accurate rapid diagnostic techniques and confirmatory tests, along with improving access to care, treatment, awareness, and screening, would contribute to controlling the spread of HIV in the country.

High Drug Resistance Levels Compromise the Control of HIV Infection in Pediatric and Adult Populations in Bata, Equatorial Guinea.

A lack of HIV viral load (VL) and HIV drug resistance (HIVDR) monitoring in sub-Saharan Africa has led to an uncontrolled circulation of HIV-strains with drug resistance mutations (DRM), compromising antiretroviral therapy (ART). This study updates HIVDR data and HIV-1 variants in Equatorial Guinea (EG), providing the first data on children/adolescents in the country. From 2019−2020, 269 dried blood samples (DBS) were collected in Bata Regional Hospital (EG) from 187 adults (73 ART-naïve/114 ART-treated) and 82 children/adolescents (25 HIV-exposed-ART-naïve/57 ART-treated). HIV-1 infection was confirmed in Madrid by molecular/serological confirmatory tests and ART-failure by VL quantification. HIV-1 pol region was identified as transmitted/acquired DRM, predicted antiretroviral susceptibility (Stanfordv9.0) and HIV-1 variants (phylogeny). HIV infection was confirmed in 88.1% of the individuals and virological failure (VL > 1000 HIV-1-RNA copies/mL) in 84.2/88.9/61.9% of 169 ART-treated children/adolescents/adults. Among the 167 subjects with available data, 24.6% suffered a diagnostic delay. All 125 treated had experienced nucleoside retrotranscriptase inhibitors (NRTI); 95.2% were non-NRTI (NNRTI); 22.4% had experienced integrase inhibitors (INSTI); and 16% had experienced protease inhibitors (PI). At sampling, they had received 1 (37.6%), 2 (32%), 3 (24.8%) or 4 (5.6%) different ART-regimens. Among the 43 treated children−adolescents/37 adults with sequence, 62.8/64.9% carried viruses with major-DRM. Most harbored DRM to NNRTI (68.4/66.7%), NRTI (55.3/43.3%) or NRTI+NNRTI (50/33.3%). One adult and one child carried major-DRM to PI and none carried major-DRM to INSTI. Most participants were susceptible to INI and PI. DRM was absent in 36.2% of treated patients with VL > 1000 cp/mL, suggesting adherence failure. TDR prevalence in 59 ART-naïve adults was high (20.3%). One-half (53.9%) of the 141 subjects with pol sequence carried CRF02_AG. The observed high rate of ART-failure and transmitted/acquired HIVDR could compromise the 95-95-95-UNAIDS targets in EG. Routine VL and resistance monitoring implementation are mandatory for early detection of ART-failure and optimal rescue therapy selection ART regimens based on PI, and INSTI can improve HIV control in EG.