Informative Questions and Answers at TheBody.com

Gynecomastia problems: http://www.thebody.com/Forums/AIDS/Aging/Q223555.html

Shingles Vaccine for HIV+ People:
http://www.thebody.com/Forums/AIDS/Aging/Q222619.html

Recently Diagnosed with HIV:
http://www.thebody.com/Forums/AIDS/Nutrition/Q223309.html

Taking Egrifta and Gaining Weight:
http://www.thebody.com/Forums/AIDS/Nutrition/Q223414.html

How Do I Improve my Sperm Count?
http://www.thebody.com/Forums/AIDS/Nutrition/Q223473.html

Wormwood and HIV
http://www.thebody.com/Forums/AIDS/Nutrition/Q223420.html

Parotid Gland Inflammation and HIV
http://www.thebody.com/Forums/AIDS/Nutrition/Q221140.html

Winstrol (Anabolic Steroid) and HIV Medications
http://www.thebody.com/Forums/AIDS/Nutrition/Q220965.html

Other Options for Lipodystrophy Besides Egrifta
http://www.thebody.com/Forums/AIDS/Nutrition/Q221875.html

How to Gain Muscle
http://www.thebody.com/Forums/AIDS/Nutrition/Q217583.html

Frailty & Muscle Loss Increase Mortality & Are Common in HIV+

Subject: NATAP/CROI: Frailty/Muscle Loss in HIV Increases Mortality & is Common

NATAP http://natap.org/
_______________________________________________



Frailty & Muscle Loss Increase Mortality & Are Common in HIV+

from Jules Levin at CROI Live in Seattle. This poster session is a
breakthrough in that it is identifying that muscle loss & frailty are
fairly common in HIV+ persons & they increase mortality. AND HCV & HBV
contribute to frailty in one study below.read this:

"Frailty is a significant predictor of mortality among both HIV+ and
at-risk IDU....... Impaired functional capacity is strongly associated
with lower bone density and lower muscle mass in middle-aged HIV-1+
persons......Co-morbidity Is Predictive of Muscle Strength in HIV+
Veterans: Results from the VACS Index....
Overall, 40% of SUN study participants aged ≤50 years with
well-controlled HIV infection were pre-frail or frail. The significant
association of pre-frailty and frailty with a history of opportunistic
infection suggests earlier diagnosis of HIV infection and prevention of
opportunistic infections may reduce risk for frailty.......Prevalence
of low muscle mass increases with age. The highest prevalence was found
in the 41- to 50-year age group. Predictors of FFMi change appear to be
associated with age, lipoatrophy recovery, and time. FFMi is associated
with all-cause mortality in HIV+ patients, suggesting that this
biological entity can provide prognostic information, in HIV+
patients..........We have recently demonstrated that patients with
prior exposure to nucleoside analog ARV, which inhibit DNA
polymerase-γ, accumulate acquired mitochondrial DNA (mtDNA) mutations
in skeletal muscle, in an apparent acceleration of the process seen in
normal aging. Here we explore an in vivo functional correlate in aging
HIV+ patients. Abnormalities of resting muscle pH handling have been
associated with fatigue and may contribute to functional decline in
this patient group."



Frailty and Pre-frailty in a Contemporary Cohort of HIV+ Adults

Nur Onen*1, P Patel2, J Baker3, L Conley2, J Brooks2, T Bush2, M
Kojic4, J Hammer5, E Overton6, and SUN Study Investigators

1Washington Univ Sch of Med in St Louis, MO, US; 2CDC, Atlanta, GA, US;
3Hennepin County Med Ctr, Univ of Minnesota, Minneapolis, US; 4Miriam
Hosp, Providence, RI, US; 5Denver Infectious Disease Consultants, CO,
US; and 6Univ of Alabama at Birmingham, US

Background:  HIV+ persons can become prematurely pre-frail and frail;
however, pre-frailty prevalence and risk factors for both frail and
pre-frail states have not been fully elucidated.

Methods:  Using data from a contemporary prospective observational
cohort of HIV+ adults (SUN Study), we determined the percentages of
non-frail, pre-frail, and frail participants at the most recent study
visit by the respective presence of 0, 1 to 2, and ≥3 of 5 established
frailty criteria as shown in the table. We evaluated associations with
pre-frailty/frailty using logistic regression analysis.

Results:  Of 308 SUN Study participants assessed—79% men, 58%
non-Hispanic white, median age 47 years (interquartile range 41 to 53),
95% on combination ART, median CD4 cell count 650 cells/mm3 (IQR 467 to
799), and 93% HIV RNA <400 copies/mL—57% were non-frail, 38% pre-frail,
and 5% frail (61%, 36%, and 4%, respectively, among the 199 [65%]
participants aged ≤50 years). Prevalence of frailty criteria are
presented in the table; exhaustion and physical inactivity
predominated. In multivariate analysis, pre-frail/frail vs non-frail
participants were more likely of non-white race/ethnicity (54% vs 33%;
adjusted odds ratio 3.24; 95% confidence interval 1.78 to 5.91), to
have had an AIDS-defining opportunistic infection (35% vs 15%; aOR
2.55, 95%CI 1.29 to 5.02), to have poorer median perceived health
scores on the SF-12 health survey (1, IQR 1 to 2 vs 2, IQR 1 to 3; aOR
2.12, 95%CI 1.49 to 3.03), to have higher median PHQ-9 depression
scores (6, IQR 2 to 11 vs 3, IQR 0 to 5; aOR 1.11, 95%CI 1.04 to 1.18)
and to be older (median age 48 years, IQR 44 to 54 vs 46 years, IQR 40
to 52; aOR 1.04, 95%CI 1.01 to 1.07). Lower CD4 cell count nadir,
female sex, and unemployment were not independently associated with
pre-frailty/frailty.

Conclusions:  Overall, 40% of SUN study participants aged ≤50 years
with well-controlled HIV infection were pre-frail or frail. The
significant association of pre-frailty and frailty with a history of
opportunistic infection suggests earlier diagnosis of HIV infection and
prevention of opportunistic infections may reduce risk for frailty.
Racial disparities warrant further investigation.
-------------------

Low Muscle Mass in HIV+ Patients: Prevalence, Predictors, and Clinical
Implication

Giovanni Guaraldi*1, S Zona1, A Silva2, G Orlando1, F Carli1, A
Santoro1, N Crupi2, G Ligabue1, C Mussi1, and L Ferruci3

1Univ of Modena and Reggio Emilia, Italy; 2Hosp de Joaquim Urbano,
Porto, Portugal; and 3Natl Inst on Aging, NIH, Baltimore, MD, US

Background:  In HIV+ patients, muscle mass measured as fat free mass
index (FFMi = FFM/h2) in DXA has never been characterized in large
epidemiological cohorts. We aimed:  to describe the prevalence of low
muscle mass using t- and z-score, per age decades, defined as <–2 SD
from the mean FFMi for an Italian Caucasian population, respectively,
for the same age or in the age strata 30 to 39 years; to identify
predictors of FFMi change; and to assess the association between FFMi
and all-cause mortality in a large HIV+ cohort.

Methods:  This observational prospective study included all consecutive
patients from 2005 to 2011 who underwent at least 2 DXA scans,
performed 1 year apart. Univariate and multivariable longitudinal
linear regressions were built to evaluate FFMI change-associated
factors. Co-variates included in the models were:  age, sex, body mass
index (BMI), physical activity; change in leg fat percentage (assessed
with DXA), in visceral adipose tissue (VAT), and in total adipose
tissue of the abdomen (TAT) (assessed with abdominal CT); NRTI, NNRTI,
and PI cumulative exposure; CD4 nadir and recovery; vitamin D plasma
level; and time between DXA scans. A Cox model was built to predict the
impact of FFMi on all cause mortality after adjustment for age and sex.

Results:  A total of 1696 HIV+ patients (1046 men) were analyzed.
Median observation follow-up period was 3.5 years (IQR 2 to 5); 96% of
patients were on ART, and during the follow-up period 37 died. BMI
change and FFMI change appeared stable over time (ß = 0.001, p = 0.111;
ß = 0.001, p = 0.070, respectively). In men, the prevalence of low
muscle mass using t- and z-scores was 0.2% and 8.5%, respectively. In
women, the prevalence of low muscle mass using t- and z-scores was 0%
and 1.5%, respectively. The highest prevalence of low muscle mass was
detected in the 41- to 50-year age group strata (t-score 0.5% and
z-score 16%). Predictors of FFMi change were:  age (ß = –0.01, p =
0.002), change of leg fat percentage (as a surrogate for lipoatrophy
recovery) (ß = –0.05, p <0.001), and time between DXA scans (ß = 0.17,
p = 0.013). FFMi was associated with all-cause mortality (HR 0.87,
95%CI 0.78 to 0.98) after adjustment for age and sex.

Conclusions:  Prevalence of low muscle mass increases with age. The
highest prevalence was found in the 41- to 50-year age group.
Predictors of FFMi change appear to be associated with age, lipoatrophy
recovery, and time. FFMi is associated with all-cause mortality in HIV+
patients, suggesting that this biological entity can provide prognostic
information, in HIV+ patients.
---------------------

Frailty Predicts Mortality in a Cohort of HIV+ and At-risk IDU

Damani Piggott*, A Muzaale, S Mehta, T Brown, S Leng, and G Kirk

Johns Hopkins Univ, Baltimore, MD, US

Background:  Frailty, a syndrome of diminished physiologic reserve with
increased stressor vulnerability, predicts hospitalization, disability,
and mortality in older HIV– adults. We have previously observed a
significant association between frailty and HIV+, particularly advanced
HIV infection, among injection drug users (IDU). In this study, we
evaluated the impact of frailty on mortality in a cohort of aging HIV+
and at-risk IDU.

Methods:  Frailty was assessed biannually from 2005 to 2008 among
current and former IDU in the ALIVE cohorts and was defined by the
presence of ≥3 of 5 standard criteria:  weakness (grip strength), slow
gait speed, weight loss, low physical activity, and exhaustion. Cox
proportional hazards models with time-varying co-variates were used to
estimate the risk (hazard ratios with 95% confidence intervals) for
all-cause mortality among frail persons relative to their robust
counterparts (defined by the absence of any criteria) and to non-frail
persons.

Results:  For 1230 subjects at baseline, the median age was 48 years,
89% were African American, 418 (34%) were female, and 351 (29%) were
HIV+. The prevalence of frailty was 9%, while 31% met no frailty
criteria. In Cox multivariable analysis of 3365 person-visits,
increasing age and HIV status were associated with increased mortality
risk. Adjusting for age, race/ethnicity, gender, educational level, and
HIV status, frail persons had a 3.4-fold increased risk of death
relative to robust persons (HR 3.42, 95%CI 1.66 to 7.03). In stratified
analysis, increased mortality risk with frailty was observed among both
HIV– persons (HR 2.91, 95%CI 1.06 to 7.96) and HIV+ persons (HR 4.05,
95%CI 1.39 to 11.8). Controlling for advanced HIV infection (CD4 <350,
HIV RNA+), frailty remained a significant predictor of mortality (HR
3.13, 95%CI 1.25 to 7.82). In comparison to non-frail persons, similar
associations of frailty with mortality were observed.

Conclusions:  Frailty is a significant predictor of mortality among
both HIV+ and at-risk IDU. Frailty provides prognostic information even
when accounting for advanced HIV disease suggesting that standardized
assessment may inform prediction of significant clinical endpoints.
Further exploration of the biological mechanisms and clinical utility
of frailty may aid management of aging HIV+ persons.
------------------------

Mitochondrial Function in vivo in Aging HIV+ Patients

Brendan Payne*1,2, M Trenell2, K Hollingsworth2, J Baxter3, V Lee4, E
Wilkins3, A Price1, and P Chinnery2

1Royal Victoria Infirmary, Newcastle upon Tyne, UK; 2Newcastle Univ,
Newcastle upon Tyne, UK; 3Northern Manchester Gen Hosp, UK; and
4Manchester Royal Infirmary, UK

Background:  We have recently demonstrated that patients with prior
exposure to nucleoside analog ARV, which inhibit DNA polymerase-γ,
accumulate acquired mitochondrial DNA (mtDNA) mutations in skeletal
muscle, in an apparent acceleration of the process seen in normal
aging. Here we explore an in vivo functional correlate in aging HIV+
patients.

Methods:  We recruited older HIV+ patients in clinical care (n = 24;
age 48 to 74 years) and age-matched controls (HIV–). Phosphorus
magnetic resonance spectroscopy (31P-MRS) was performed using a 3-T
scanner. Spectra were obtained from gastrocnemius/soleus at rest and
during recovery from brief exercise. Key measures were:  adenosine
triphosphate (ATP) production during recovery (as Qmax (ADP), maximal
rate of adenosine diphosphate (ADP) clearance; τ1/2 (PCr), half-life of
phosphocreatine); and pH handling. In HIV+ subjects, comparison was
made with cellular mitochondrial function by COX (cytochrome c oxidase)
histochemistry of lower-limb muscle biopsy.

Results:  Basal parameters of ATP metabolism differed between subjects
groups:  ADP (mean ±SD) HIV+ 10.2±0.7 mM, HIV– 9.5±0.5 mM (p = 0.001);
PCr HIV+ 41.0±15.2 mM, HIV– 30.7±2.1 mM (p = 0.003). Furthermore, basal
ADP levels in HIV+ subjects correlated with biopsy COX defect (r =
0.45, p = 0.032). In contrast, dynamic measures of ATP production
during exercise recovery were similar in HIV+ and control subjects:
Qmax (ADP) (mean±SD) HIV+ 26.6±18.6 mM/min, HIV– 23.0±10.2 mM/min; τ1/2
(PCr) HIV+ 29.9±13.4 s, HIV– 27.5±8.3 s. There was more variance seen
in the HIV+ than the HIV– group, however no disease or treatment
variable was significantly correlated with ATP production rate, nor was
cellular COX defect. HIV+ subjects showed disordered pH handling
compared with HIV– controls as evidenced by higher basal pH (mean±SD,
7.07±0.03 vs 7.04±0.02, p = 0.001) and post-recovery pH (7.09±0.03 vs
7.06±0.02, p = 0.008) but similar exertional minimum pH (6.98±0.13 vs
7.00±0.03, ns). Resting pH correlated with COX defect (r = 0.42, p =
0.044).

Conclusions:  The altered basal ATP metabolite levels in HIV+ subjects
coupled with preserved dynamic function, despite cellular mitochondrial
defects on biopsy, suggests functional compensation to an acquired
mtDNA defect, once therapy has been switched to a cleaner agent.
Abnormalities of resting muscle pH handling have been associated with
fatigue and may contribute to functional decline in this patient group.
-----------------------

Functional Impairment Is Associated with Low Bone and Muscle Mass in
Middle-aged HIV-1+ Persons

Kristine Erlandson*, A Allshouse, C Jankowski, S MaWhinney, W Kohrt,
and T Campbell
Univ of Colorado Denver, Aurora, US

Background:  Physical function impairment may be accelerated in the
presence of osteoporosis, obesity, or sarcopenia. HIV+ persons have
early physical impairment, but little is known about the contributions
of bone or body composition changes to impairment in persons aging with
HIV-1.

Methods:  We conducted a prospective study of 45- to 65-year-old HIV-1+
subjects who had been on ART >6 months and whose plasma HIV-1 RNA <48
copies/mL. Low functioning (LF) and high functioning (HF) subjects were
identified by deficits on both Fried’s frailty criteria and the Short
Physical Performance Battery and were matched by age, gender, and time
since HIV diagnosis. Bone, fat, and muscle were assessed by
densitometry. Osteoporosis was defined as T-score ≤–2.5, osteopenia as
T-score <–1 but >–2.5, sarcopenia as appendicular skeletal muscle index
(ASMI) <5.45 kg/m2 (female) and <7.26 kg/m2 (male). Insulin-like growth
factor (IGF)-1 and IGF-binding protein (BP)-3 were measured. Stratified
logistic regression for categorical variables and linear mixed effects
regression for continuous variables were estimated to account for
correlation within matched pairs. Body mass index (BMI), tobacco, and
nadir CD4+ T cells were adjusted in models of bone loss.

Results:  We identified 30 LF and matched them to 48 HF subjects; mean
age 52.7 years, CD4 T cell 598, 96% HIV-1 viral load <48 copies/mL, 18%
female, 77% white, 17% Hispanic. LF and HF were similar in age,
duration of ART, tenofovir use, and CD4 T- cells (all p >0.2). LF
subjects had significantly lower BMD and T scores at the hip and spine;
differences remained significant in multivariate analyses. Although all
persons with BMI <18.5 kg/m2 were LF, LF trended toward higher relative
body fat content. LF subjects had a greater prevalence of sarcopenia
(50% vs 25%, p = 0.04), lower lean mass, and lower IGF-1/IGFBP3.

Conclusions:  Impaired functional capacity is strongly associated with
lower bone density and lower muscle mass in middle-aged HIV-1+ persons. 
Whether bone or muscle loss is the result of disuse due to impairment,
or if low muscle or bone mass, mediated through effects of IGF-1, leads
to impairment by progressive weakness or inflammatory pathways remains
to be established. Further studies should investigate the role of
increased muscle/bone mass and increased IGF-1 on preserving functional
independence as persons with HIV age.
--------------------------

Co-morbidity Is Predictive of Muscle Strength in HIV+ Veterans: Results
from the VACS Index

Krisann Oursler*1, J Tate2, T Gill2, K Crothers3, T Brown4, S Crystal5,
J Womack2, D Leaf6, J Sorkin1, A Justice2, and Veterans Aging Cohort
Study Project Team

1Univ of Maryland Sch of Med and Publ Hlth and VA Maryland Hlthcare
System, Baltimore, US; 2Yale Univ Sch of Med and Publ Hlth and VA
Connecticut Hlthcare System, New Haven, US; 3Univ of Washington,
Seattle, US; 4Johns Hopkins Univ, Baltimore, MD, US; 5Rutgers Univ, New
Brunswick, NJ, US; and 6Univ of California, Los Angeles Sch of Med and
Greater Los Angeles VA Hlthcare System, US

Background:  Despite improved survival, HIV+ adults have increased risk
for physical disability due to muscle weakness, poor ambulatory
function, and low cardiorespiratory fitness. The objective of this
study was to determine whether the VACS Index, a comprehensive index of
generalized organ injury based on routine clinical laboratory data, is
associated with hand-grip and leg-strength, 6-minute walk distance, and
cardiorespiratory fitness (peak oxygen consumption, VO2 peak).

Methods:  HIV+ patients enrolled in the Veterans Aging Cohort Study
(VACS) participated in this cross-sectional study at the Baltimore VA
Medical Center from 2004 to 2007. The VACS Index was calculated
incorporating hemoglobin, FIB-4, eGFR, hepatitis C infection, CD4
count, HIV-1 viral load, and age; higher score reflected greater
co-morbidity. Analyses included nonparametric correlation (Spearman’s
rank) and linear regression models.

Results:  We included 2 women and 53 men:  91% African American race,
mean age of 52 (SD 7) years. The VACS Index was inversely correlated
with hand-grip strength (r = –0.36, p = 0.01) and lower extremity
strength (quadriceps, r = –0.45, p <0.01), but was not significantly
associated with 6-minute walk distance (r = –0.26, p = 0.07) or VO2
peak (r = –0.13, p = 0.3). A 20-point higher VACS Index score was
associated with a 10% lower leg strength (mean 76 newtons; 95%CI –124
to –29; p <0.001; see the figure), which remained significant after
adjustment for muscle cross-sectional area (p = 0.04). The VACS Index
explained 34% of the variance in specific leg strength. In contrast, an
index restricted to CD4 count, viral load, and age did not correlate
with any of these measures (p >0.08).

Conclusions:  In this sample of predominantly African American men
ranging in age from 31 to 72 years, the VACS Index was significantly
associated with upper and lower extremity strength. The VACS Index may
be valuable for identification of patients at high risk for disability
due to muscle weakness. Association of Leg Strength with the VACS Index.

Doctors Seek Way to Treat Muscle Loss

Nandrolone can do this easily, as long as doctors have a very close monitoring on hematocrit since older men tend to have more problems with polycythemia

http://www.nytimes.com/2010/08/31/health/research/31muscle.html?adxnnl=1&adxnnlx=1283259693-/5OVKCtiMHD2uTxULb30yQ

Vitamin and Mineral Use in HIV- Summary of Studies

 Excellent summary tables on the use of micronutrients in HIV published in

Am J Clin Nutr 2007;85:333–45. Printed in USA. © 2007 American Society for Nutrition

http://www.ajcn.org/cgi/content/full/85/2/333

Reference	Study design, location, and population	Vitamin concentrations1	Results and conclusions
Cross-sectional studies
Toma et al, 2001 (93)	Cross-sectional study in Canada. 11 HIV-positive adults (6 receiving HAART for 3 y, 5 not receiving any HIV medications).	Vitamin A: HAART (51 ± 5 µg/dL); no HIV medications (66 ± 11 µg/dL)	Mean plasma concentrations of vitamin A and retinol-binding protein were significantly lower (P = 0.03) and higher (P = 0.04), respectively, in those receiving HAART.
Rousseau et al, 2000 (94)	Cross-sectional study in France. 30 HIV-positive adults, mostly injection-drug users (23 receiving HAART for3 y, 7 not receiving HAART).	Vitamin A: total (0.66 ± 1.2 µmol/L); 24 of 30 (80%) deficient (<1.5 µmol/L); concentrations not presented for HAART and non-HAART groups Vitamin E: total (9.24 ± 3.4 mg/L); 10 of 29 (34%) deficient (<6 mg/L); concentrations not presented for HAART and non-HAART groups	Mean plasma concentrations of vitamins A and E were not significantly different between those with a CD4 count < and >250 cells/µL, between those with viral load > and <5000 copies/mL, and between those receiving and not receiving HAART.
Tang et al, 2000 (95)	Cross-sectional study in the United States. 175 HIV-positive injection-drug users (30 receiving HAART, 65 receiving dual- or monotherapy, 80 not receiving any HIV medications).	-Tocopherol2: HAART (1076 ± 468 µg/dL); no HIV medications (778 ± 209 µg/dL) -Carotene3: HAART (1.06 ± 0.01 µg/dL); no HIV medications (0.74 ± 0.02 µg/dL) ß-Carotene2: HAART (8.8 ± 3.1 µg/dL); no HIV medications (5.2 ± 0.9 µg/dL) Vitamin A2: HAART (42.0 ± 11.4 µg/dL); no HIV medications (38.4 ± 6.2 µg/dL) -Tocopherol2: HAART (238 ± 107 µg/dL); no HIV medications (202 ± 59 µg/dL)	Adjusted mean serum concentrations of-tocopherol (P = 0.0008), -carotene (P= 0.05), and ß-carotene (P = 0.02), but not of vitamin A and -tocopherol, were significantly higher in those receiving HAART than in those not taking any HIV medications; no significant differences in adjusted mean serum vitamin concentrations between CD4 cell count categories (<200, 200–499, and 500 cells/µL).
Remacha et al, 2003 (96)	Cross-sectional study in Spain. 126 HIV-positive adults receiving HAART compared with 109 HIV-positive historical control subjects from 1989 to 1992 receiving HAART.	Folate: HAART (1473 ± 1087 mmol/L), 1 of 126 (0.8%) deficient (450 mmol/L); historical control subjects (1057 ± 665 mmol/L), 19 of 109 (17.4%) deficient Vitamin B-12: HAART (402 ± 218 pmol/L), 2 of 126 (1.2%) deficient (150 pmol/L); historical control subjects (330 ± 219 pmol/L), 20 of 109 (18%) deficient	Mean concentrations of red blood cell folate and serum vitamin B-12 were significantly higher in HIV-positive adults receiving HAART than in historical HIV-positive control subjects receiving HAART. Significantly fewer HIV-positive adults receiving HAART than historical control subjects had folate or vitamin B-12 deficiencies.
Woods et al, 2003 (97)	Cross-sectional study from 1995 to 2000 in the United States. 412 HIV-positive adults (615 patient-time intervals in adults receiving HAART, 454 patient-time intervals in adults not receiving HAART).	Vitamin B-124: HAART [491 (382–667) pg/mL], 17% deficient (<350 pg/mL); no HAART [462 (369–617) pg/mL], 22% deficient	Median serum concentration of vitamin B-12 was significantly higher at the beginning of each patient-time interval in HIV-positive adults receiving HAART; multivariate analyses were not performed to account for higher intakes of vitamin B-12 (P = 0.0002) in participants receiving HAART.
Longitudinal studies
Look et al, 2001 (98)	Longitudinal study from 1997 to 1998 in Germany. 17 HIV-positive adults studied at baseline and 100 d after HAART initiation.	Vitamin B-6: baseline [11.9 (10.7–13.2) µmol/L]; follow-up [15.7 (8.8–22.7) µmol/L] Folate: baseline [3.8 (1.0–6.5) ng/mL]; follow-up [5.2 (1.8–8.5) ng/mL] Methylmalonic acid (surrogate of vitamin B-12)3: baseline [138 (100–176) µmol/L]; follow-up [186 (81–291) µmol/L]	Median follow-up serum concentrations of vitamin B-6, folate, and methylmalonic acid were not significantly higher than median baseline concentrations; however, baseline concentrations of vitamin B-6, folate, and methlymalonic acid were not significantly different from those of a cohort of HIV-negative healthy control subjects.

 Observational studies of minerals in HIV-infected persons receiving highly active antiretroviral therapy (HAART)

Reference Study design, location, and population Mineral concentrations Results and conclusions Cross-sectional studies     Batterham et al, 2001 (99) Cross-sectional study in Australia. 48 HIV-positive adults (35 receiving HAART, 13 not receiving any HIV medications). Selenium: HAART with detectable (>400 copies/mL) viral load (2.16 ± 0.54 µmol/L); HAART with undetectable viral load (2.22 ± 0.93 µmol/L); no HIV medications (2.40 ± 0.83 µmol/L) Mean serum concentrations of glutathione peroxidase (P = 0.001), lipid peroxidase (P = 0.03), and uric acid (P = 0.009), but not of selenium, were significantly different between HIV-positive persons receiving HAART and those not taking any HIV medications.     Wellinghausen et al, 2000 (100) Cross-sectional study in Germany. 79 HIV-positive adults (52 receiving HAART; 4 receiving dual- or monotherapy, 23 not receiving any HIV medications). Zinc: HAART (12.5 ± 2.8 µmol/L), 25% deficient (<10.5 µmol/L); no HIV medications (12.7 ± 2.7 µmol/L), 22% deficient Zinc concentrations were not significantly different between those receiving and those not receiving HAART. Longitudinal studies     Rousseau et al, 2000 (94) Longitudinal study from 1995 to 1998 in France. 44 HIV-positive adults, mostly injection-drug users. At baseline, none were receiving HAART, but 80% were receiving dual-combination therapy. Of 30 participants with follow-up data, 23 were receiving HAART and 7 were not receiving any HIV medications. Selenium: baseline (51.5 ± 15.6 µg/L), 77% deficient (<60 µg/L); follow-up (93.9 ± 21.6 µg/L), 10% deficient Iron: baseline (15.5 ± 5.6 µmol/L), 19% deficient (<11 µmol/L); follow-up (19.0 ± 16 µmol/L), 13% deficient Zinc: baseline (79.0 ± 22.8 µmol/L), 23% deficient (<75 µmol/L); follow-up (71.2 ± 16 µmol/L), 27% deficient Copper: baseline (149 ± 16 µg/100 mL), 98% overloaded (>140 µg/100 mL); follow-up (144 ± 95 µg/100 mL), 43% overloaded Mean serum concentrations of selenium, iron, zinc, and copper did not significantly increase from baseline; however, significantly fewer participants had selenium deficiency and copper overload at follow-up; at follow-up, mean concentrations of selenium, iron, zinc, and copper were not significantly different between those receiving and those not receiving HAART.

Intervention studies of micronutrients in HIV-infected persons receiving highly active antiretroviral therapy (HAART)

Reference Study design, population, and inclusion and exclusion criteria Intervention Primary outcomes Major findings Conclusions Nonrandomized trials     McComsey et al, 2003 (101) Nonrandomized, open-label pilot study without placebo control in the United States. 10 HIV-positive adults receiving HAART for 12 mo. 9 had lipoatrophy and 1 had sustained hyperlactemia at enrollment. Daily vitamin C (1000 mg) and vitamin E (800 IU) and twice-daily N-acetyl cysteine (600 mg) for 24 wk. Fasting glucose, insulin resistance, peripheral fat, lipoatrophy, CD4 cell count, plasma viral load Intervention significantly increased fasting glucose and insulin resistance and decreased waist-to-hip ratio compared with placebo; intervention had no significant effect on peripheral fat, lipoatrophy, CD4 cell count, or plasma viral load. 24 wk of a supplement worsened fasting glucose and insulin resistance and did not significantly improve peripheral fat, lipoatrophy, immunologic status, or plasma viral load.     Batterham et al, 2001 (99) Nonrandomized trial without placebo control in Australia. 66 HIV-positive adults enrolled and 48 completed study (32 receiving HAART, 3 receiving dual therapy, 13 not receiving any HIV medications). Exclusion criteria included taking supplements within 4 wk of enrollment, not clinically stable or with active infection, and change of HIV medication regimen within 6 wk of enrollment. Daily supplementation with either a low-dose1 or a high- dose2antioxidant regimen for 12 wk. Antioxidant defense (glutathione, glutathione peroxidase), oxidative stress (allantoin, uric acid), plasma viral load Intervention significantly increased concentrations of glutathione and glutathione peroxidase from baseline, but had no significant effect on allantoin, uric acid, or plasma viral load; no significant differences between those receiving low-dose and those receiving high-dose regimens. 12 wk of an antioxidant supplement increased oxidative defenses, but did not affect oxidative stress or plasma viral load. Randomized trials     Jensen-Fangel et al, 2003 (102) Randomized crossover trial without placebo control in Denmark. 15 HIV-positive adults receiving HAART; all with chronic nelfinavir-associated diarrhea. Twice-daily calcium carbonate (1350 mg) f or 14 d. A subset of 6 patients additionally treated with twice-daily calcium gluconate (2950 mg) and an extra 300 mg calcium carbonate. Clinical improvement of diarrhea Intervention had no significant effect on clinical measurements of diarrhea. 14 d of a calcium carbonate supplement did not clinically improve nelfinavir-associated diarrhea.     Spada et al, 2002 (103); De Souza et al, 2005 (104) Randomized, placebo-controlled trial in Brazil. 29 HIV-positive adults with CD4 count <500 cells/µL. 26 initiated HAART and 3 initiated dual-combination therapy at study enrollment. Daily vitamin E (800 mg -tocopherol) for 6 mo. Lymphocyte viability, CD4 cell count, CD4: CD8 cells, plasma viral load Intervention had no significant effect on CD4 cell count, CD4: CD8 cells, or plasma viral load as compared with placebo; intervention significantly increased lymphocyte viability compared with placebo. 6 mo of vitamin E supplementation improved lymphocyte viability, but did not affect immune cell count or plasma viral load.     Jaruga et al, 2002 (105) Randomized, placebo-controlled trial in Poland. 30 HIV-positive adults receiving HAART. Daily vitamin A (5000 IU), vitamin C (50 mg), and vitamin E (100 IU) for 6 mo. Antioxidant defense (catalase, superoxide dismutase) oxidative stress; (thiobarbituric acid–reactive substances); CD4 cell count Intervention significantly increased concentrations of catalase and superoxide dismutase and significantly lowered thiobarbituric acid–reactive substances; the CD4 cell count increased in the intervention group from baseline, whereas the mean CD4 count of the placebo group decreased, but the difference was not statistically significant. 6 mo of an antioxidant multivitamin supplement significantly increased antioxidant defenses, significantly reduced oxidative stress, and possibly improved immunologic status.     Burbano et al, 2002 (106) Randomized placebo-controlled trial in the United States. 186 HIV-positive injection-drug users (85 receiving HAART, 39 receiving dual- or monodrug therapy, 52 not receiving any HIV medications). Daily selenium (200 µg) for 2 y. CD4 cell count, hospital admissions Significantly fewer participants in the intervention group than in the placebo group had a decrease in CD4 cell count of >50 cells/µL during the study; intervention significantly reduced hospital admissions because of opportunistic infections and other HIV-related conditions; in multivariate analyses,3the placebo group had a 2.4 greater risk of hospitalization (P = 0.01). 2 y of a selenium supplement decreased large reductions in CD4 cell count and reduced the risk of hospitalization.     Kaiser et al, 2006 (107) Randomized placebo-controlled trial in the United States. 40 HIV-positive adults receiving HAART. Micronutrient supplementation twice daily for 12 wk.4 Fasting glucose, insulin, lipids, CD4 cell count, plasma viral load Intervention significantly increased absolute CD4 cell count (P = 0.03) and mean change in CD4 cell count from baseline (P= 0.01) and had no significant effects on fasting glucose, insulin, lipids, or plasma viral load. 12 wk of micronutrient supplementation increased CD4 cell count.

¹ Included 5450 IU ß-carotene, 250 mg vitamin C, 100 IU vitamin E, 100 µg Se, 50 mg coenzyme Q10, 10 mg thiamine, 25 mg vitamin B-6, 55 mg pantothenic acid, 250 µg folate, 50 µg vitamin B-12, and 5 mg Zn.

² Included 21800 IU ß-carotene, 1000 mg vitamin C, 400 IU vitamin E, 200 µg Se, 200 mg coenzyme Q10, 40 mg thiamine, 100 mg vitamin B-6, 220 mg pantothenic acid, 1000 µg folate, 200 µg vitamin B-12, and 20 mg Zn.

³ Multivariate analysis adjusted for HAART (yes or no), use of other HIV medications (yes or no), age >50 y, CD4 cell count at baseline, and plasma viral load >10000 copies/mL at baseline.

⁴ Micronutrient supplement included 1200 mg N-acetyl cysteine, 1000 mg acetyl L-carnitine, 400 mg -lipoic acid, 20000 IU ß-carotene, 8000 IU vitamin A, 1800 mg vitamin C, 60 mg thiamine, 60 mg riboflavin, 60 mg pantothenic acid, 60 mg niacinamide, 60 mg inositol, 260 mg vitamin B-6, 2.5 mg vitamin B-12, 400 IU vitamin D, 800 IU vitamin E, 800 µg folic acid, 800 mg Ca, 400 mg Mg, 200 µg Se, 150 µg I, 30 mg Zn, 2 mg Cu, 2 mg B, 99 mg K, 18 mg Fe, 10 mg Mn, 50 µg biotin, 100 µg Cr, 300 µg Mo, 60 mg choline, 300 mg bioflavonoid complex, 100 mg L-glutamine, and 150 mg betaine HCL.