The authors have declared that no competing interests exist.
Phytochemicals (PHT) are a large group of biologically active plant chemicals that may have positive effects on human health such as immune system stimulation, down regulation of inflammatory responses, radical scavenging activities, cell repair function, and antibacterial and antiviral activity. In this proof of principle 6 months study, the effects of supplementing a PHT mix, Phyto V7, to HIV-1 seropositive individuals and AIDS patients were examined. Individuals with CD4+ T-cells below 350 counts/mm3were assigned to one of the following treatments: CG1 - no treatment, CG2 - only highly active antiretroviral treatment (HAART), TG1 - only Phyto V7, and TG2- both Phyto V7 and HAART. After 3 months of treatment there were approximately (-)1%, 1%, 2% and 4% increase in the mean weight of the CG1, CG2, TG1 and TG2 groups, respectively. The tendency for the body mass index (BMI) was similar. The CD4+ counts increased by 13%, 39%, 53% and 35%, respectively. Similar trends were noted after 6 months with 2%, 79%, 53% and 69% increases in the CD4+ counts, respectively. There was a significant reduction in viremia only in groups receiving HAART. Overall better results were obtained in the group of patients receiving both HAART and Phyto V7, in which the mean weight increased by 5.7% and the CD4+ T-cell counts increased by 69% after 6 months. This study indicates that providing Phyto V7 to HIV-1 seropositive individuals and AIDS patients, receiving or not receiving HAART, improves their physical wellbeing and CD4+ counts, enabling them to cope better with the viral infection.
HIV infection and AIDS are endemic in many malnourished populations. A balanced nourishing diet is fundamental for healthiness and survival for all individuals, including for HIV-infected individuals. Tuberculosis and diarrhea, which occur in many HIV infected individuals, cause by themselves appetite loss, atrophy and weight loss. In HIV-infected individuals, the body energy requirements are higher than in non-HIV infected individuals
Almost in all randomized controlled trials that studied the effects of MMN supplementation found increased CD4+ T-cell counts or reduced mortality in the group of HIV-infected persons receiving MMN as compared to the HIV-infected persons receiving placebo
Phytochemicals, chemical compounds that occur naturally in plants, serve as micronutrients. Importantly, some phytochemicals also have additional important beneficial properties, as demonstrated in several clinical studies. For example, some phytochemicals possess radical scavenging activities
Phyto V7 is a specific mix of phytochemicals that has been found to have immune-stimulating properties. This was demonstrated in two separate studies. In the first one, administration of Phyto V7 to chicks vaccinated against Newcastle Disease Virus resulted in enhanced humoral immune responses against the virus
In the current study we studied the clinical and immunological effects of the administration of Phyto V7 on HIV-1 seropositive individuals and AIDS patients, in order to determine if this phytochemical complex may be an important nutritional component to be given to these populations.
This was a prospective, controlled clinical trial designed to determine the effect of Phyto V7 supplementation on HIV-1 disease progression in HIV-infected individuals receiving or not receiving HAART. It consisted of an Intervention Test Group and a Non Intervention Control Group (
Enrollment took place between December 2009 and February 2010 in Hospital de Clínicas, Universidad Nacional de Córdoba, city of Cordoba, Argentina. Clinical interview, anthropometric and hematological analysis were performed prior to enrollment. Only diagnosed HIV-1 seropositive patients with less than 350 CD4+ T-cells per mm³, who had never received ART, were enrolled. Individuals with co-current infections or positive to hepatitis antibodies were excluded. Written informed consent was obtained from all study participants after explaining the trial aims and specifics in detail. Randomization to each of the detailed groups above was guided by the expressed will of the patient. A total of 28 patients were enrolled and divided into 4 groups as detailed in
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Number | 7 | 8 | 7 | 6 |
Sex (Male/Female) | 6/1 | 5/3 | 5/2 | 5/1 |
Age (mean±SD) male | 33±8 | 37±8 | 31±7 | 43±10 |
Age (mean±SD) female | 54 | 42±9 | 28±3 | 46 |
Age (range) male | 26-44 | 29-49 | 22-39 | 33-57 |
Age (range) female | 54 | 33-51 | 25-30 | 46 |
BMI male | 22±1 | 22±1 | 24±2 | 21±3 |
BMI female | 21 | 22±2 | 22±0.2 | 23 |
CDC Classification | A2 all | A2 all | A2-6, A3-1 | A2-5, C2-1 |
CD4 cells/mm3(mean±SD) | 295±32 | 271±42 | 276±38 | 233±74 |
CD4 cells/mm3 (range) | 237-336 | 203-350 | 175-329 | 93-298 |
Ln Viral load (mean±SD) | 10.11±1.22 | 10.59±0.7 | 10.78±0.96 | 10.35±1.99 |
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1 | CG1 | None | None | Asymptomatic |
2 | CG1 | None | None | Asymptomatic |
3 | CG1 | None | None | Candidiasis |
4 | CG1 | None | None | Asymptomatic |
5 | CG1 | None | None | Microsporidium |
6 | CG1 | None | None | Asymptomatic |
7 | CG1 | None | None | Asymptomatic |
8 | CG2 | None | Lamivudine/Zidovudine/Efavirenz | Asymptomatic |
9 | CG2 | None | Lamivudine/Abacabir/Efavirenz | Tuberculosis |
10 | CG2 | None | Lamivudine/Zidovudine/Nevirapine | Asymptomatic |
11 | CG2 | None | Lamivudine/Zidovudine/Nevirapine | Asymptomatic |
12 | CG2 | None | Abacabir/Tenofovir/Nevirapine | Asymptomatic |
13 | CG2 | None | Lamivudine/Zidovudine/Nevirapine | Asymptomatic |
14 | CG2 | None | Lamivudine/Zidovudine/Nevirapine | Pneumocystis Jiroveci |
15 | CG2 | None | Abacabir/Tenofovir/Nevirapine | Asymptomatic |
16 | TG1 | Yes | None | Asymptomatic |
17 | TG1 | Yes | None | Asymptomatic |
18 | TG1 | Yes | None | Asymptomatic |
19 | TG1 | Yes | None | Asymptomatic |
20 | TG1 | Yes | None | Tuberculosis |
21 | TG1 | Yes | None | Asymptomatic |
22 | TG1 | Yes | None | Asymptomatic |
23 | TG2 | Yes | Lamivudine/Zidovudine/Nevirapine | Asymptomatic |
24 | TG2 | Yes | Lamivudine/Didanosine/Nevirapine | Asymptomatic |
25 | TG2 | Yes | Lamivudine/Zidovudine/Efavirenz | Epigastric distress |
26 | TG2 | Yes | Abacabir/Tenofovir/Nevirapine | Asymptomatic |
27 | TG2 | Yes | Abacabir/Tenofovir/Nevirapine | Candidiasis |
28 | TG2 | Yes | Lamivudine/Zidovudine/Nevirapine | Asymptomatic |
The Statistical Analysis Plan included the group mean, median and range analysis. The standard deviation (SD <10 and> 90) was performed by comparing the mobility of indicators in each case with longitudinal monitoring, average and increased by cuttings. For n = 28, validation sample was subjected to Yates Chi Square, giving a confidence interval of 95% (CI = 95) with a value α = 0.05, P = 0.2432. The delta % change in the weight or BMI of the patients after 3 and 6 months was calculated using the following equation (Weight or BMI at 3 or 6 months/Weight or BMI at baseline) x100-100. A Paired T-test was used to compare the means before and after treatment within groups. A Student T-test and/or a Mann-Whitney Rank Sum Test was used to compare between the changes in the weight, BMI and CD4+ T-cell counts between the groups. ANOVA of Kruskal & Wallis analyses and Conover post-test were used to compare the patient’s characteristics at the onset of the trial. SigmaPlot 12.0 software was used to conduct the above statistical tests.
Twenty eight patients were recruited to the study and assigned into 4 groups as detailed in
After 3 months from the commencement of the Trial it became clear that there were obvious differences between the physical wellbeing of the patients in the different groups. This was especially noticeable in the increase in the weight of the patients (
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Mean | 0 | 65 | 70.37 | 69.43 | 67.67 |
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3 | 64.27 | 70.76 | 70.54 | 70 | |
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6 | 64.24 | 71.27 | 70.8 | 71.55 | |
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Median | 0 | 65 | 68.5 | 67 | 64 |
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3 | 65.4 | 69 | 67.3 | 67.5 | |
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6 | 65 | 69.3 | 67.7 | 71.5 | |
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SDs | 0 | 5.38 | 9.53 | 10.2 | 12.1 |
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3 | 5.86 | 9.76 | 10.39 | 11.49 | |
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6 | 6.37 | 10.2 | 10.39 | 11.14 | |
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Mean | 0 | 21.69 | 22.3 | 22.86 | 21.44 |
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3 | 21.45 | 22.42 | 23.23 | 22.18 | |
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6 | 21.43 | 22.57 | 23.32 | 22.68 | |
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Median | 0 | 21.72 | 22.56 | 21.97 | 21.39 |
3 | 22.04 | 22.74 | 22.4 | 21.9 | ||
6 | 22.1 | 22.82 | 22.51 | 22.87 | ||
SDs | 0 | 1.15 | 1.43 | 1.73 | 2.43 | |
3 | 1.41 | 1.51 | 1.82 | 2.11 | ||
6 | 1.52 | 1.63 | 1.81 | 2 |
The patients in all 4 groups had similar significant high viral loads with no statistically significant differences in the group mean viremia at the beginning of the Trial (
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0 | 10.11 | 10.59 | 10.78 | 10.35 |
3 | 9.79 | 3.91* | 9.58 | 5.34 | ||
6 | 10.77 | 3.91 | 9.47 | 3.91 | ||
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0 | 10.16 | 10.42 | 11.16 | 10.84 | |
3 | 9.78 | 3.91 | 10.52 | 3.91 | ||
6 | 11.04 | 3.91 | 10.04 | 3.91 | ||
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0 | 1.22 | 0.7 | 0.96 | 1.99 | |
3 | 0.44 | 0.0 | 2.58 | 3.19 | ||
6 | 0.81 | 0.0 | 2.64 | 0.0 | ||
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0 | 295 | 271 | 276 | 233 |
3 | 335 | 378 | 424 | 315 | ||
6 | 300 | 485 | 428 | 394 | ||
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0 | 297 | 266 | 274 | 255 | |
3 | 351 | 377 | 434 | 330 | ||
6 | 328 | 495 | 401 | 402 | ||
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0 | 32.2 | 42.2 | 38.5 | 73.7 | |
3 | 68 | 107.6 | 172.5 | 173.6 | ||
6 | 75.5 | 141.1 | 119.1 | 170.8 |
As depicted in
This study demonstrates that the oral administration of a phytochemical complex (Phyto V7) is beneficial to HIV-1 seropositive individuals and AIDS patients, whether receiving antiretroviral therapy or not. There were quantitative improvements in the patients receiving Phyto V7 in their weight, BMI and CD4+ T-cell counts. While there was a mean decrease in the weight and BMI of the patients that did not receive any treatment during the trial, in the patients that received only Phyto V7 there was a significant increase in the weight and BMI both after 3 and 6 months of the study. Interestingly, in the patients that received only ARV treatment, there was a statistical significant increase in weight and BMI only after 6 months of treatment, as compared to the patients that did not receive any treatment. The most notorious increases in weight and BMI were noted in the patients that received both ARV treatment and Phyto V7. Meaningfully, there was a clear statistical difference between the increase in weight and BMI in those patients that received ARV treatment only and those that received the ARV and also the phytochemicals both at 3 and 6 months (
The HAART regimens used in this trial were based on the recommended Argentinian Ministry of Health guidelines at the time the trial was conducted. Those regimens as well as other HAART regimens, when taken with good compliance, can effectively reduce the viral loads to undetectable levels and significantly improve prognosis and well-being of the patients, as indeed was the case in the group of patients in this study that only received the antiretroviral therapy. However, HAART may cause also significant adverse effects, such as lipodystrophy, dyslipidaemia, cardiovascular complications, central and peripheral nervous system disturbances and insulin resistance
As indicated in this study, in patients that did not receive antiretroviral treatment, the administration of Phyto V7 resulted in an increase in their CD4+ T-cell counts, weight and BMI, indicating that supplementation of this phytochemical mix may improve the capacity of HIV-1 infected individuals to cope with the viral infection and potentially delaying the need to treat them with HAART, postponing the potential complications associated with HAART treatment.
HAART treatment taken with good compliance in most cases results in viremia suppression, immune reconstitution, and reduction in incidence and severity of opportunistic diseases and death
What are the mechanisms by which the phytochemicals benefit HIV-1 seropositive and AIDS patients is not yet clear and should be elucidated. While it has been reported that some phytochemicals possess potent anti-HIV in vitro activity
Part of their positive effect can be explained as serving as micronutrients, having radical scavenging activities
Additional studies should be performed to support the notion that supplementation of phytochemicals to HIV-1 infected patients is beneficial, and to elucidate their mechanism of action. This should be done with larger cohorts of HIV-1 infected individuals and AIDS patients. In the current study only patients with less than 350 CD4+ T-cells per mm3 were recruited. Future studies should examine individuals with significantly higher CD4+ T-cell counts not receiving HAART as well as individuals with very low CD4 T-cell counts receiving or not receiving HAART. Future studies should also include patients receiving just multiple micronutrients supplementation (MMN) and compare them with patients receiving just phytochemicals. If proven the significant added value of phytochemicals over MMN, current recommendations, like the UN requested of inclusion of MMN for treatment of HIV carriers and AIDS patients at any stage of their disease, should be revised to include phytochemicals.