Unnecessary Antiretroviral Treatment Switches and Accumulation of HIV Resistance Mutations; Two Arguments for Viral Load Monitoring in Africa

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 58; no. 1; pp. 23 - 31
• Main Authors: Sigaloff, Kim C E, Hamers, Raph L, Wallis, Carole L, Kityo, Cissy, Siwale, Margaret, Ive, Prudence, Botes, Mariette E, Mandaliya, Kishor, Wellington, Maureen, Osibogun, Akin, Stevens, Wendy S, van Vugt, Michèle, Rinke de Wit, Tobias F
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 01-09-2011; Lippincott Williams & Wilkins; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Adult; Africa - epidemiology; AIDS/HIV; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - therapeutic use; Antiretroviral drugs; Biological and medical sciences; Cohort Studies; Cross-Sectional Studies; Drug Administration Schedule; Drug resistance; Drug Resistance, Viral - genetics; Drug Substitution; Drug therapy; Female; Fundamental and applied biological sciences. Psychology; HIV; HIV Infections - drug therapy; HIV Infections - epidemiology; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; Human immunodeficiency virus; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Mutation; RNA, Viral - blood; Treatment Failure; Viral diseases; Viral Load; Virology; Africa; Sub-Saharan Africa; Antiretroviral agent; Viremia; Africa; Retroviridae; Lentivirus; Infection; Virus; Resistance; Treatment; HIV; Viral disease; highly active antiretroviral therapy; Antiviral; Mutation; Human immunodeficiency virus; drug resistance; Viral load
• ISSN: 1525-4135; 1944-7884
• DOI: 10.1097/QAI.0b013e318227fc34

OBJECTIVES:This study aimed to investigate the consequences of using clinicoimmunological criteria to detect antiretroviral treatment (ART) failure and guide regimen switches in HIV-infected adults in sub-Saharan Africa. Frequencies of unnecessary switches, patterns of HIV drug resistance, and risk factors for the accumulation of nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations were evaluated.
METHODS:Cross-sectional analysis of adults switching ART regimens at 13 clinical sites in 6 African countries was performed. Two types of failure identification were compareddiagnosis of clinicoimmunological failure without viral load testing (CIF only) or CIF with local targeted viral load testing (targeted VL). After study enrollment, reference HIV RNA and genotype were determined retrospectively. Logistic regression assessed factors associated with multiple thymidine analogue mutations (TAMs) and NRTI cross-resistance (≥2 TAMs or Q151M or K65R/K70E).
RESULTS:Of 250 patients with CIF switching to second-line ART, targeted VL was performed in 186. Unnecessary switch at reference HIV RNA <1000 copies per milliliter occurred in 46.9% of CIF only patients versus 12.4% of patients with targeted VL (P < 0.001). NRTI cross-resistance was observed in 48.0% of 183 specimens available for genotypic analysis, comprising ≥2 TAMs (37.7%), K65R (7.1%), K70E (3.3%), or Q151M (3.3%). The presence of NRTI cross-resistance was associated with the duration of ART exposure and zidovudine use.
CONCLUSIONS:Clinicoimmunological monitoring without viral load testing resulted in frequent unnecessary regimen switches. Prolonged treatment failure was indicated by extensive NRTI cross-resistance. Access to virological monitoring should be expanded to prevent inappropriate switches, enable early failure detection and preserve second-line treatment options in Africa.