Peripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial.
Sensory peripheral neuropathy (PN) remains a common complication in HIV-positive patients despite effective combination anti-retroviral therapy (ART). Data on PN on second-line ART is scarce. We assessed PN using a standard tool in patients failing first-line ART and for 96 weeks following a switch to PI-based second-line ART in a large Randomised Clinical Trial in Sub-Saharan Africa. Factors associated with PN were investigated using logistic regression. Symptomatic PN (SPN) prevalence was 22% at entry (N = 1,251) and was associated (p < 0.05) with older age (OR = 1.04 per year), female gender (OR = 1.64), Tuberculosis (TB; OR = 1.86), smoking (OR = 1.60), higher plasma creatinine (OR = 1.09 per 0.1 mg/dl increase), CD4 count (OR = 0.83 per doubling) and not consuming alcohol (OR = 0.55). SPN prevalence decreased to 17% by week 96 (p = 0.0002) following similar trends in all study groups (p = 0.30). Asymptomatic PN (APN) increased over the same period from 21 to 29% (p = 0.0002). Signs suggestive of PN (regardless of symptoms) returned to baseline levels by week 96. At weeks 48 and 96, after adjusting for time-updated associations above and baseline CD4 count and viral load, SPN was strongly associated with TB (p < 0.0001). In summary, SPN prevalence was significantly reduced with PI-based second-line therapy across all treatment groups, but we did not find any advantage to the NRTI-free regimens. The increase of APN and stability of PN-signs regardless of symptoms suggest an underlying trend of neuropathy progression that may be masked by reduction of symptoms accompanying general health improvement induced by second-line ART. SPN was strongly associated with isoniazid given for TB treatment.
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, Aviation House, 125 Kingsway, London, WC2B 6NH, UK. A.Arenas-Pinto@ucl.ac.uk.
Alejandro
http://orcid.org/0000-0002-3368-5005
A
Arenas-Pinto
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, Aviation House, 125 Kingsway, London, WC2B 6NH, UK.
Jennifer
J
Thompson
University of Zimbabwe Clinical Research Centre, Harare, Zimbabwe.
Godfrey
G
Musoro
Joint Clinical Research Centre (JCRC), Kampala, Uganda.
Hellen
H
Musana
Joint Clinical Research Centre (JCRC), Mbarara, Uganda.
Abbas
A
Lugemwa
Infectious Diseases Institute, Makerere University, Kampala, Uganda.
Andrew
A
Kambugu
University Teaching Hospital, Lusaka, Zambia.
Aggrey
A
Mweemba
Joint Clinical Research Centre (JCRC), Kakira, Uganda.
Dickens
D
Atwongyeire
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, Aviation House, 125 Kingsway, London, WC2B 6NH, UK.
Margaret J
MJ
Thomason
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, Aviation House, 125 Kingsway, London, WC2B 6NH, UK.
A Sarah
AS
Walker
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, Aviation House, 125 Kingsway, London, WC2B 6NH, UK.|National University of Singapore, Singapore, Singapore.
Nicholas I
NI
Paton
D000328:Adult; D017954:Africa South of the Sahara; D064829:Alcohol Abstinence; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology / Q000821:virology; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D016015:Logistic Models; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology; D012367:RNA, Viral / Q000037:antagonists & inhibitors / Q000097:blood*; D000068898:Raltegravir Potassium / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use*; D012907:Smoking / Q000503:physiopathology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy; D019562:Viral Load / Q000187:drug effects
D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D004338:Drug Combinations; D012367:RNA, Viral; C558899:lopinavir-ritonavir drug combination; D061466:Lopinavir; D000068898:Raltegravir Potassium; D019438:Ritonavir; D007538:Isoniazid
Africa; HIV; Peripheral neuropathy; Second-line ART; Tuberculosis