TY - JOUR
T1 - Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy
T2 - A randomised controlled trial
AU - Andersen, Aase Bengaard
AU - Thurnham, David
AU - Tomkins, Andrew
AU - Mussa, Kelvin
AU - Masilingi, Charles
AU - Fue, Elizabeth
AU - Masesa, Eva
AU - Mpandachalo, Neema
AU - Kanunga, Anne
AU - Munalula, Likando
AU - Kapinda, Brenda
AU - Sikanyika, Nellie
AU - Mngara, Julius
AU - Ogweno, George
AU - Ikigo, Piu
AU - Muchimba, Mutinta
AU - Samwinga, Memory
AU - Beacroft, Leo
AU - Black, Harry
AU - Smith, Celeste Gregg
AU - Chisenga, Caroline
AU - Hebie, Marlene
AU - Munkombwe, Derek
AU - Sampson, Gemma
AU - Fernandez, Yolanda
AU - Wandore, Gunda
AU - Jonas, Aswile
AU - Mabuda, Hildah Banda
AU - Adugna, Wakwoya
AU - Makandilo, Stephen
AU - Mubita, Mwangana
AU - Mulenga, Jessy
AU - Filteau, Suzanne
AU - PrayGod, George
AU - Kasonka, Lackson
AU - Woodd, Susannah
AU - Rehman, Andrea M.
AU - Chisenga, Molly
AU - Siame, Joshua
AU - Koethe, John R.
AU - Changalucha, John
AU - Michael, Denna
AU - Kidola, Jeremiah
AU - Manno, Daniela
AU - Larke, Natasha
AU - Yilma, Daniel
AU - Heimburger, Douglas C.
AU - Friis, Henrik
AU - Kelly, Paul
N1 - Publisher Copyright:
© 2015 Filteau et al.
PY - 2015/1/28
Y1 - 2015/1/28
N2 - Background: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. Methods: The study was an individually-randomised phase III trial conducted in ART clinics in Mwanza, Tanzania, and Lusaka, Zambia. Participants were 1,815 ART-naïve non-pregnant adults with body mass index (BMI) <18.5kg/m2 who were referred for ART based on CD4 count <350 cells/μL or WHO stage 3 or 4 disease. The intervention was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30g/day (150kcal) from recruitment until 2weeks after starting ART and 250g/day (1,400kcal) from weeks 2 to 6 after starting ART. The primary outcome was mortality between recruitment and 12weeks of ART. Secondary outcomes were serious adverse events (SAEs) and abnormal electrolytes throughout, and BMI and CD4 count at 12weeks ART. Results: Follow-up for the primary outcome was 91%. Median adherence was 66%. There were 181 deaths in the LNS group (83.7/100 person-years) and 184 (82.6/100 person-years) in the LNS-VM group (rate ratio (RR), 0.99; 95% CI, 0.80-1.21; P = 0.89). The intervention did not affect SAEs or BMI, but decreased the incidence of low serum phosphate (RR, 0.73; 95% CI, 0.55-0.97; P = 0.03) and increased the incidence of high serum potassium (RR, 1.60; 95% CI, 1.19-2.15; P = 0.002) and phosphate (RR, 1.23; 95% CI, 1.10-1.37; P <0.001). Mean CD4 count at 12weeks post-ART was 25 cells/μL (95% CI, 4-46) higher in the LNS-VM compared to the LNS arm (P = 0.02). Conclusions: High-dose vitamin and mineral supplementation in LNS, compared to LNS alone, did not decrease mortality or clinical SAEs in malnourished African adults initiating ART, but improved CD4 count. The higher frequency of elevated serum potassium and phosphate levels suggests high-level electrolyte supplementation for all patients is inadvisable but the addition of micronutrient supplements to ART may provide clinical benefits in these patients.
AB - Background: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. Methods: The study was an individually-randomised phase III trial conducted in ART clinics in Mwanza, Tanzania, and Lusaka, Zambia. Participants were 1,815 ART-naïve non-pregnant adults with body mass index (BMI) <18.5kg/m2 who were referred for ART based on CD4 count <350 cells/μL or WHO stage 3 or 4 disease. The intervention was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30g/day (150kcal) from recruitment until 2weeks after starting ART and 250g/day (1,400kcal) from weeks 2 to 6 after starting ART. The primary outcome was mortality between recruitment and 12weeks of ART. Secondary outcomes were serious adverse events (SAEs) and abnormal electrolytes throughout, and BMI and CD4 count at 12weeks ART. Results: Follow-up for the primary outcome was 91%. Median adherence was 66%. There were 181 deaths in the LNS group (83.7/100 person-years) and 184 (82.6/100 person-years) in the LNS-VM group (rate ratio (RR), 0.99; 95% CI, 0.80-1.21; P = 0.89). The intervention did not affect SAEs or BMI, but decreased the incidence of low serum phosphate (RR, 0.73; 95% CI, 0.55-0.97; P = 0.03) and increased the incidence of high serum potassium (RR, 1.60; 95% CI, 1.19-2.15; P = 0.002) and phosphate (RR, 1.23; 95% CI, 1.10-1.37; P <0.001). Mean CD4 count at 12weeks post-ART was 25 cells/μL (95% CI, 4-46) higher in the LNS-VM compared to the LNS arm (P = 0.02). Conclusions: High-dose vitamin and mineral supplementation in LNS, compared to LNS alone, did not decrease mortality or clinical SAEs in malnourished African adults initiating ART, but improved CD4 count. The higher frequency of elevated serum potassium and phosphate levels suggests high-level electrolyte supplementation for all patients is inadvisable but the addition of micronutrient supplements to ART may provide clinical benefits in these patients.
KW - Antiretroviral therapy
KW - Body mass index
KW - Electrolytes
KW - HIV
KW - Malnutrition
KW - Micronutrients
UR - http://www.scopus.com/inward/record.url?scp=84924404860&partnerID=8YFLogxK
U2 - 10.1186/s12916-014-0253-8
DO - 10.1186/s12916-014-0253-8
M3 - Article
SN - 1741-7015
VL - 13
JO - BMC Medicine
JF - BMC Medicine
IS - 1
M1 - 17
ER -