Subtype variability, virological response and drug resistance assessed on dried blood spots collected from HIV patients on antiretroviral therapy in Angola

• Published in: Journal of antimicrobial chemotherapy Vol. 61; no. 3; pp. 694 - 698
• Main Authors: Garrido, Carolina, Zahonero, Natalia, Fernándes, Diana, Serrano, Dulcelina, Silva, Ana Rita, Ferraria, Nelia, Antúnes, Francisco, González-Lahoz, Juan, Soriano, Vincent, de Mendoza, Carmen
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2008; Oxford Publishing Limited (England)
• Subjects: Adult; Angola - epidemiology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - methods; Biological and medical sciences; Chemotherapy; DBS; Drug resistance; Drug Resistance, Viral - genetics; Female; HIV; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - genetics; HIV subtypes; HIV-1 - classification; HIV-1 - genetics; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Medical sciences; non-B subtypes; Pharmacology. Drug treatments; Retrospective Studies; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; viral load; Angola; Africa; HIV subtypes; viral load; DBS; non-B subtypes; Human; Immunopathology; Biological fluid; Antiretroviral agent; Treatment resistance; Typing; Variability; Retroviridae; AIDS; Immune deficiency; Lentivirus; Blood; Infection; Virus; Chemotherapy; Treatment; Viral disease; Antiviral; Human immunodeficiency virus; Viral load; Subtype
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/dkm515

Background Subtype variability may influence treatment response and selection of drug resistance mutations in HIV-positive patients on antiretroviral therapy. Patients and methods A retrospective study was performed on specimens collected on dried blood spots (DBS) from HIV-positive individuals receiving antiretroviral therapy in Luanda, Angola. HIV-RNA, drug resistance mutations and subtypes were examined in 294 HIV-positive patients treated with two nucleoside analogues (NA) plus one non-nucleoside reverse transcriptase inhibitor (NNRTI). Results Overall, 217 (74%) had <1000 HIV-RNA copies/mL after a median of 12 months (range 7–24) of therapy. CD4 count was significantly higher in subjects with undetectable viraemia compared with viraemic patients (294 versus 220 cells/mm3; P = 0.003). Reverse transcriptase and/or gp41 genes could be genotyped in only 45 (58%) of viraemic patients, probably due to poor storage conditions of DBS. The most frequent resistance mutations were M184V (70%) and K103N (39%); 65% had mutations conferring resistance to both NA and NNRTI. Only five patients did not show resistance mutations. A wide HIV-1 subtype heterogeneity was found: 6 C (18.2%), 2 F (6%), 2 H (6%), 1 D (3%), 1 G (3%), 8 CRF02_AG (24.2%), 2 CRF06 (6%), 1 CRF01_AE (3%), 1 CRF14_BG (3%), 1 CRF25 (3%) and 1 CRF19 (3%). HIV clade could not be assigned in 7 (21%). Conclusions Nearly three-quarters of HIV-positive individuals who began an NNRTI-based triple regimen in Angola showed undetectable viraemia after a median of 12 months of therapy, a rate similar to that reported in Western countries. Specimens collected on DBS may allow monitoring of treatment response in resource-limited regions, although adequate temperature and humidity storage conditions are important to ensure RNA stability and further successful testing.