Survey: Most patients with HIV lipodystrophy are willing to inject Egrifta once a day to reduce their visceral fat

 LIPODYSTROPHY TREATMENT- PATIENT ACCEPTANCE
DownloadCreate Chart1. Has your belly fat increased after starting HIV medications?
answered question 85
skipped question
2
Response
Percent
Response
Count
Yes
92.9% 79
No
7.1% 6
DownloadCreate Chart2. Would you be willing to inject a drug daily under your skin in your belly to decrease your belly fat by 13% in 26 weeks?
answered question 87
skipped question
0
Response
Percent
Response
Count
Yes
83.9% 73
No
16.1% 14

Impact of Lipodystrophy on Quality of Life of People Living With HIV- Survey Results

1. How old are you?
  answered question 1,325
 
skipped question
6
  Response
Percent
Response
Count
Under 15 years old
0.3% 4
15-20
0.2% 2
20-25
0.5% 7
25-30
1.7% 23
30-35
4.8% 63
35-40
7.8% 104
40-45
23.1% 306
45-50
22.6% 299
50-55
20.8% 275
55-60
11.4% 151
Over 60
6.9% 91
DownloadCreate Chart2. What is your ethinicity?
  answered question 1,325
 
skipped question
6
  Response
Percent
Response
Count
White
78.4% 1,039
Black
7.7% 102
Latino
9.1% 121
Asian
1.7% 22
American Indian
0.8% 10
Other
2.3% 31
DownloadCreate Chart3. What is your gender?
  answered question 1,325
 
skipped question
6
  Response
Percent
Response
Count
Female
12.4% 164
Male
87.2% 1,155
Transgender
0.5% 6
DownloadCreate Chart4. How long have you known that you are HIV positive?
  answered question 1,325
 
skipped question
6
  Response
Percent
Response
Count
Under 5 years
10.1% 134
5- 10 years
14.1% 187
10-15 years
20.8% 276
15-20 years
27.7% 367
over 20 years
27.2% 361
DownloadCreate Chart5. Are you currently taking HIV medications?
  answered question 1,325
 
skipped question
6
  Response
Percent
Response
Count
Yes
94.9% 1,258
No
5.1% 67
DownloadCreate Chart6. If you are taking or have taken medications for HIV, how long have you taken them (total years)?
  answered question 1,288
 
skipped question
43
  Response
Percent
Response
Count
Under 5 years
15.0% 193
5-10 years
21.1% 272
10-15 years
35.3% 455
15-20 years
28.6% 368
DownloadCreate Chart7. Have you taken any of these medications in the past?
  answered question 1,170
 
skipped question
161
  Response
Percent
Response
Count
Zerit (D4T)
83.6% 978
AZT
78.7% 921
Crixivan
50.3% 589
High dose Norvir
37.1% 434
Hydroxyurea
11.2% 131
DDI (videx)
55.0% 644
DDC (Hivid)
29.4% 344
DownloadCreate Chart8. Have you had body shape changes after starting HIV medications in the past?
  answered question 1,331
 
skipped question
0
  Response
Percent
Response
Count
Yes
88.7% 1,180
No
11.3% 151
DownloadCreate Chart9. What kind of body changes are you experiencing or have you experienced?
  answered question 1,296
 
skipped question
35
  Response
Percent
Response
Count
Involuntary weight loss/wasting
45.8% 594
Abdominal (Belly) Fat Gain
61.9% 802
Facial Wasting
79.9% 1,035
Butt Wasting
70.3% 911
Veiny Legs or Arms
68.5% 888
Increased Breast Size
21.1% 274
Buffalo Hump (Behind The Neck)
20.9% 271
Increased Neck Size
16.4% 213
Parotid Gland Enlargement (sides of face)
15.7% 203
Other
6.4% 83
Show repliesIf other, please specify 106
DownloadCreate Chart10. Have you experienced depression or anxiety due to the body changes?
  answered question 1,331
 
skipped question
0
  Response
Percent
Response
Count
Yes
88.4% 1,177
No
11.6% 154
DownloadCreate Chart11. Have you ever thought of killing yourself due to your body changes?
  answered question 1,331
 
skipped question
0
  Response
Percent
Response
Count
Yes
26.3% 350
No
73.7% 981
DownloadCreate Chart12. Have you ever thought about not taking your HIV medications or have you ever stopped taking them because of fear of worsening your body changes?
  answered question 1,331
 
skipped question
0
  Response
Percent
Response
Count
Yes
42.4% 564
No
57.6% 767
DownloadCreate Chart13. Have the body changes cause you to: (check all that apply)
  answered question 1,256
 
skipped question
75
  Response
Percent
Response
Count
Stop socializing and going out to meet people
67.4% 847
Stop dating
51.8% 651
Decrease sexual activity
73.9% 928
Increase sexual activity
3.9% 49
Worry too much about people finding out you are HIV+
61.2% 769
Be rejected by potential sexual partners
56.0% 703
Affect your job performance
27.4% 344
Stop looking at yourself in the mirror
58.0% 729
Change your clothing style
56.0% 703
Abuse drugs or alcohol to feel better
18.2% 228
Deplete your finances in search of a solution
29.2% 367
Other
6.7% 84
Show repliesPlease Specify 112
DownloadCreate Chart14. What have you done to try to reverse your body changes? (check all that apply)
  answered question 1,242
 
skipped question
89
  Response
Percent
Response
Count
Exercised more
72.6% 902
Watch what I eat
72.4% 899
Got my face injected with a filler or cosmetic product
40.7% 505
Got my parotid glands treated with radiation
1.4% 18
Took supplements that I heard may help my body fat/muscle
43.0% 534
Used testosterone
45.0% 559
Used human growth hormone
17.1% 212
Used nandrolone (Deca durabolin)
16.1% 200
Used Oxandrin
13.8% 171
Got liposuction
7.2% 90
Got butt implants
1.7% 21
Use padded underwear
13.3% 165
Other
6.6% 82
Show repliesIf other, please specify 118
DownloadCreate Chart15. Have your insurance, ADAP/Ryan White clinic, HMO, health care system (for countries outside the US) and/or supplier patient assistance program paid for ANY of the solution(s) mentioned in the answer(s) in the previous question? (Check all that apply)
  answered question 1,124
 
skipped question
207
  Response
Percent
Response
Count
No one has. I had to pay with my own money
63.2% 710
Yes, my insurance company has
17.7% 199
Yes, my HMO has
4.7% 53
Yes, my ADAP/Ryan White program has
6.9% 78
Yes, my country’s health system has
7.9% 89
Yes, a supplier’s patient assistance program has
11.1% 125
Show repliesPlease specify what was paid for 279
DownloadCreate Chart16. Have you had facial wasting (lipoatrophy)?
  answered question 1,330
 
skipped question
1
  Response
Percent
Response
Count
Yes
80.3% 1,068
No
19.7% 262
DownloadCreate Chart17. What option have you used to improve your facial lipoatrophy? (check all that apply)
  answered question 1,144
 
skipped question
187
  Response
Percent
Response
Count
I have done nothing
41.3% 472
I have used BioAlcamid
7.1% 81
I have used silicone
6.8% 78
I have used Sculptra (New Fill or polylactic acid)
29.6% 339
I have used Radiesse
5.2% 60
I have used PMMA in Rio, Tijuana or other
4.4% 50
I have switched off from Zerit to Viread, Ziagen, Epzicom or Truvada
31.0% 355
I have switched off from AZT to Viread, Ziagen, Epzicom, or Truvada
12.3% 141
I have taken Uridine (Nucleomaxx)
1.1% 13
Other
8.4% 96
Show repliesplease specify 157
PAGE: PAGE 2
DownloadCreate Chart18. Do you have or have you had high cholesterol/triglycerides?
  answered question 1,297
 
skipped question
34
  Response
Percent
Response
Count
Yes
65.8% 853
No
28.0% 363
I do not know
6.2% 81
DownloadCreate Chart19. Have you had or do you have higher than normal blood glucose (sugar)?
  answered question 1,297
 
skipped question
34
  Response
Percent
Response
Count
Yes
27.4% 356
No
58.7% 761
I do not know
13.9% 180
DownloadCreate Chart20. Have you heard from your doctor or other sources that belly fat, high LDL (bad) cholesterol, high triglycerides or high blood sugar may affect your health and mortality?
  answered question 1,297
 
skipped question
34
  Response
Percent
Response
Count
Yes
75.5% 979
No
19.8% 257
I do not remember
4.7% 61
DownloadCreate Chart21. Do you think some HIV medications can increase belly fat?
  answered question 1,296
 
skipped question
35
  Response
Percent
Response
Count
Yes
81.8% 1,060
No
0.6% 8
Not sure
15.6% 202
I think HIV causes it, not the medications
2.0% 26
DownloadCreate Chart22. Do you think some HIV medications can increase fat loss under the skin (facial wasting, veiny legs/arms, fat loss in the butt)?
  answered question 1,296
 
skipped question
35
  Response
Percent
Response
Count
Yes
88.8% 1,151
No
0.8% 11
Not sure
6.9% 89
I think HIV causes it, not the medications
3.5% 45
Download23. What do you want me to tell or ask lipodystrophy researchers about what the research needs are for that problem?
  answered question 690
 
skipped question
641
  Response
Count
Show replies 690

FDA Committee Unanimously Recommends Egrifta for Lipodystrophy

FROM POZ.COM

May 27, 2010
FDA Committee Unanimously Recommends Egrifta for Lipodystrophy

A U.S. Food and Drug Administration (FDA) advisory committee has unanimously recommended that Egrifta (tesamorelin), Montreal-based Theratechnologies’ experimental product for the treatment of excess abdominal fat in HIV-positive people with lipodystrophy, be approved by the agency.  Though the FDA is not required to follow the recommendations of its advisory committees, it usually does so.

Several of the 16 panelists making up the Endocrinologic and Metabolic Drugs Advisory Committee, which met May 27 at the University of Maryland University College (UMUC) Marriott Conference Centers in Adelphi, Maryland, stressed that there is a need for additional follow-up studies to monitor the long-term safety and efficacy of the drug.

Egrifta is a synthetic human growth hormone-releasing factor. Phase III clinical trials of the drug indicate that it decreases visceral adipose tissue (VAT)—fat deep within the belly—by about 17 percent.

According to Christian Marsolais, MD, vice president of clinical research and medical affairs at Theratechnologies, who reviewed the Phase III efficacy results at today’s hearing, 57.4 percent of patients taking Egrifta experienced an 8 percent or greater reduction in VAT—the primary goals of the studies—compared with 29.3 percent of the placebo group.

Unlike Serostim (recombinant human growth hormone), an earlier contender for treating excess VAT, Egrifta has long been suggested to have fewer side effects when used for at least a year, including a minimal effect on blood sugar (glucose) levels.

There were, however, conflicting reports at today’s hearing regarding the risk of diabetes in people receiving Egrifta in the Phase III clinical trials.

Graziella Soulban, MD, director of clinical research at Theratechnologies, reported higher rates of pre-diabetes and diabetes among those receiving Egrifta, compared with placebo, during the first 26 weeks of the studies. But between weeks 26 and 52 of the studies, however, the number of people with glucose intolerance and diabetes dropped. 

Ali Mohamadi, MD, a clinical reviewer from the FDA, unveiled a slightly more detailed analysis. According to the FDA safety analysis reported this morning, 49.2 percent of patients receiving Egrifta had no instances of raised blood-glucose levels. However, 17.3 percent of those receiving Egfrifta had three or more increased blood-glucose measurements during the clinical trial, compared with 7.3 percent of those receiving placebo.

Mohamadi also reported that 25 percent of patients in the tesamorelin group who started off as pre-diabetic eventually went on to develop frank diabetes in the studies. Among those who began treatment without a history of diabetes and had normal glucose levels, Mohamadi confirmed, the risk of diabetes during the study remains low.

Increases in insulin-like growth factor 1, or IGF-1, was another safety issue discussed at length during today’s meeting. Though increases in IGF-1 are considered to be an indicator of Egrifta’s activity, IGF-1 has also been suggested to promote tumor growth, which can be problematic in a population of individuals—including people living with HIV—who already face a higher risk of cancer. According to Mohamadi, a third of patients receiving Egrifta had significantly elevated IGF-1 levels. However, according to Soulban, these increases were not found to be associated with an increased risk of any type of cancer in the 52-week Phase III studies.

Mohamadi reiterated that decreases in decreases in VAT associated with the use of Egrifta have not been shown to decrease the risk of cardiovascular disease—an important potential benefit of any drug that treats abdominal obesity—and several panelists reiterated that future studies should explore this goal. And though the panelists were divided on the data submitted to the FDA regarding improvements in body image and body perception in the studies, many were clearly impressed by the mid-day public testimony offered by three people living with HIV—Jeff Berry of the AIDS Treatment Activists Coalition and two Egrifta clinical trial participants—who emphasized the detrimental effects of lipodystrophy in people living with HIV.

As the clock approached 4 p.m., the final vote was cast by the advisory committee members, in response to a single question put forth by the FDA: Does the risk-benefit assessment support approval of Egrifta? Sixteen voted “yes”—there were zero “no” votes and no abstentions.

Several panelists stressed that follow-up data should be collected to better understand the long-term risks of glucose abnormalities and IGF-1 increases. Theratechnologies noted that it is already planning a safety monitoring program that will go into effect if the FDA agrees with the advisory committee panel and approves the drug for use in the United States.

A final decision from the FDA is expected within the next two months. The agency has until July 27 to notify Theratechnologies of the drug’s approval status and of any post-marketing studies that must be conducted.

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




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 for≤3 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).
{alpha}-Tocopherol2: HAART (1076 ± 468 µg/dL); no HIV medications (778 ± 209 µg/dL) {alpha}-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) {gamma}-Tocopherol2: HAART (238 ± 107 µg/dL); no HIV medications (202 ± 59 µg/dL)
Adjusted mean serum concentrations of{alpha}-tocopherol (P = 0.0008), {alpha}-carotene (P= 0.05), and ß-carotene (P = 0.02), but not of vitamin A and {gamma}-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 {alpha}-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 {alpha}-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.

The Forgotten Minority: HIV+ Patients With No Available HIV treatment Options

Most successful HIV medication combinations require 3 medications that are fully active, but a small portion of long term survivors with long treatment history and accumulated HIV resistance mutations do not have the luxury of constructing a viable regimen to save their lives.

Several potent antiretrovirals (ARVs) in the past 4 years have enabled many patients with multidrug resistance (MDR) to suppress their HIV viral load.

Due to several factors, there is still a relatively small number of patients that have developed resistance or toxicity to the new ARV’s

To protect them from functional monotherapy, these patients are not allowed in pre- approval studies.

Some HIV ARV’s in phase II studies may potentially help those patients, but combining them after their respective approvals may take at least 3 or 4 years.

Some of these patients may be at risk of clinical decline and death if no viable regimen is available for them before 2012

We do not know how many of these patients there are in the U.S.

I performed a physician survey with the help of some researchers and activists to find out how many patients may be present in the U.S. with HIV multidrug resistance in deep salvage (one or zero active medications to treat their HIV).

These figures summarize our findings (click on figures to enlarge):

These are the HIV medications in current development. The ones with an asterisk are the ones that may work for patients with no options left.

The closest ones to approval are Taimed’s ibalizumab ( an IV once every two weeks) which may be two years away from approval, and GSK’s integrase inhibitor GSK572 (2-3 years) . Avexa recently stopped the development of   Apricitabine and Myriad may follow suit with their maturation inhibitor. A combination of at least two compounds will probably not be feasible until 2013.  Efforts towards creating an expanded access program using multiple investigational agents is currently under way but it may not be a possibility until 2011.  All companies and the FDA are welcoming the concept in its early stages.  I will provide an update during the last quarter of 2010.

I wish we could help patients who need help now.

Nelson Vergel