RESUMEN
OBJECTIVES: Previous work showed that gag-protease-derived phenotypic susceptibility to PIs differed between HIV-1 subtype CRF02_AG/subtype G-infected patients who went on to successfully suppress viral replication versus those who experienced virological failure of lopinavir/ritonavir monotherapy as first-line treatment in a clinical trial. We analysed the relationship between PI susceptibility and outcome of second-line ART in Nigeria, where subtypes CRF02_AG/G dominate the epidemic. METHODS: Individuals who experienced second-line failure with ritonavir-boosted PI-based ART were matched (by subtype, sex, age, viral load, duration of treatment and baseline CD4 count) to those who achieved virological response ('successes'). Successes were defined by viral load <400 copies of HIV-1 RNA/mL by week 48. Full-length Gag-protease was amplified from patient samples for in vitro phenotypic susceptibility testing, with PI susceptibility expressed as IC50 fold change (FC) relative to a subtype B reference strain. RESULTS: The median (IQR) lopinavir IC50 FC was 4.04 (2.49-7.89) for virological failures and 4.13 (3.14-8.17) for virological successes (P = 0.94). One patient had an FC >10 for lopinavir at baseline and experienced subsequent virological failure with ritonavir-boosted lopinavir as the PI. There was no statistically significant difference in single-round replication efficiency between the two groups (P = 0.93). There was a moderate correlation between single-round replication efficiency and FC for lopinavir (correlation coefficient 0.32). CONCLUSIONS: We found no impact of baseline HIV-1 Gag-protease-derived phenotypic susceptibility on outcomes of PI-based second-line ART in Nigeria.
Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Proteasa del VIH/genética , Carga Viral/efectos de los fármacos , Adulto , Recuento de Linfocito CD4 , Ensayos Clínicos como Asunto , Femenino , Células HEK293 , Infecciones por VIH/sangre , Proteasa del VIH/sangre , Inhibidores de la Proteasa del VIH/farmacología , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Concentración 50 Inhibidora , Riñón/citología , Riñón/efectos de los fármacos , Riñón/virología , Persona de Mediana Edad , Nigeria , Fenotipo , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
A retrospective audit of plasma human herpesvirus-8 (HHV-8) viral load testing was performed in three HIV treatment centres over 24 months. Reasons for testing (360 tests) were: symptoms of systemic inflammatory response syndrome (SIRS) (fever, lymphadenopathy and raised inflammatory markers); monitoring in known HHV-8 pathology other than Kaposi sarcoma (KS); investigation of known/suspected KS, and other/no reason. Of patients with multicentric Castleman disease (MCD), 14/16 (88%) had detectable plasma HHV-8, as did 27/45 (60%) with biopsy proven or clinically confirmed KS, and 6/19 (32%) with lymphoma. Neither of the two patients with MCD and no detectable HHV-8 had SIRS symptoms at the time of the test. There was wide variation between centres in the indications prompting HHV-8 testing, with a more conservative approach resulting in a higher proportion of positive results. Measuring plasma HHV-8 in the absence of SIRS symptoms, established HHV-8 disease monitoring, or confirmed/suspected KS is unlikely to yield detectable HHV-8 thus allowing potential cost savings.