OBJECTIVE: Treatment guidelines recommend initiation of therapy for individuals experiencing rapid CD4 cell decline. It is not known, however, whether the rate of CD4 cell decline before combination antiretroviral therapy (cART) is related to immunological response following cART. METHODS: We estimated precART and postcART CD4 cell slopes by mixed models and categorized patients into two groups according to whether estimated precART slopes were above or below the 75th percentile. We compared immunological responses of the two groups through both mixed models and survival techniques. Models were stratified by CD4 cell at baseline, adjusted for HIV RNA, age, sex, HIV transmission group, year of seroconversion, initiation during primary infection, hepatitis C virus and hepatitis B virus serostatus, and cART class. RESULTS: Of 2038 eligible patients, 1531 and 507 experienced median (interquartile range) precART CD4 cell slope of −105 (−471 to −61) and −42 (−62 to −80) cells/μl, respectively, over 2 years. After adjusting for potential confounders, individuals with shallower decline experienced a slower rate of CD4 cell recovery following cART initiation of +9.5 [95% confidence interval (CI) +6.6 to +12.2] compared to +13.9 (+13.0 to +14.8) cells/μl per month among those with steeper precART decline (P < 0.001). After stratifying by the baseline CD4 cell count, the adjusted relative hazard of an increase from baseline of more than 50 cells/μl was 0.70 (95% CI 0.62−0.79) for those with a shallower vs. steeper precART decline. CONCLUSION: Findings highlight the existence of a subgroup of individuals with shallower precART CD4 cell decline who experience poorer CD4 cell increases after cART; new studies in this group may provide information to optimize responses to therapy.
OBJECTIVE: Treatment guidelines recommend initiation of therapy for individuals experiencing rapid CD4 cell decline. It is not known, however, whether the rate of CD4 cell decline before combination antiretroviral therapy (cART) is related to immunological response following cART. METHODS: We estimated precART and postcART CD4 cell slopes by mixed models and categorized patients into two groups according to whether estimated precART slopes were above or below the 75th percentile. We compared immunological responses of the two groups through both mixed models and survival techniques. Models were stratified by CD4 cell at baseline, adjusted for HIV RNA, age, sex, HIV transmission group, year of seroconversion, initiation during primary infection, hepatitis C virus and hepatitis B virus serostatus, and cART class. RESULTS: Of 2038 eligible patients, 1531 and 507 experienced median (interquartile range) precART CD4 cell slope of −105 (−471 to −61) and −42 (−62 to −80) cells/μl, respectively, over 2 years. After adjusting for potential confounders, individuals with shallower decline experienced a slower rate of CD4 cell recovery following cART initiation of +9.5 [95% confidence interval (CI) +6.6 to +12.2] compared to +13.9 (+13.0 to +14.8) cells/μl per month among those with steeper precART decline (P < 0.001). After stratifying by the baseline CD4 cell count, the adjusted relative hazard of an increase from baseline of more than 50 cells/μl was 0.70 (95% CI 0.62−0.79) for those with a shallower vs. steeper precART decline. CONCLUSION: Findings highlight the existence of a subgroup of individuals with shallower precART CD4 cell decline who experience poorer CD4 cell increases after cART; new studies in this group may provide information to optimize responses to therapy.
Authors: Christopher J Hoffmann; James J Lewis; David W Dowdy; Katherine L Fielding; Alison D Grant; Neil A Martinson; Gavin J Churchyard; Richard E Chaisson Journal: J Acquir Immune Defic Syndr Date: 2013-05-01 Impact factor: 3.731
Authors: O T Stirrup; A J Copas; A N Phillips; M J Gill; R B Geskus; G Touloumi; J Young; H C Bucher; A G Babiker Journal: HIV Med Date: 2017-12-01 Impact factor: 3.180
Authors: Olufunke Fasawe; Carlos Avila; Nathan Shaffer; Erik Schouten; Frank Chimbwandira; David Hoos; Olive Nakakeeto; Paul De Lay Journal: PLoS One Date: 2013-03-12 Impact factor: 3.240
Authors: Joseph Sempa; Mark Ssennono; Andreas Kuznik; Mohammed Lamorde; Stefanie Sowinski; Aggrey Semeere; Sabine Hermans; Barbara Castelnuovo; Yukari C Manabe Journal: BMC Public Health Date: 2012-09-04 Impact factor: 3.295