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HIV and AIDS

Acquired Immunodeficiency Syndrome (AIDS) is a deficiency of cellular immunity brought on by infection with the human immunodeficiency virus (HIV-1) and characterized by a range of opportunistic diseases and infections. Such opportunistic infection proliferate in the absence of a robust immune response.

One of the key mechanisms that HIV fosters immune dysfunction is through completely taking over the VDR and interfering with D-binding protein. As a result, en end-stage AIDS patients levels of 1,25-D approach zero.

Vitamin D metabolism

HIV uses the VDR to recognize its own LTR promoter region in order to transcribe its own genome, thus taking over the VDR.1)

Related article: HIV and AIDS

HIV is a viral infection, and AIDS is the syndrome, which results – according to the Marshall Pathogenesis – in a dysregulated vitamin D metabolism. As evidenced by the subset of people who survive for decades with HIV, the virus itself is not necessarily deadly. Instead, it is the co-infections which are the proximate cause of the disease. One can define the breadth of AIDS-related complications by the extent and number of co-infections such as pneumonia, herpes, Candida, etc.

Supporting this hypothesis, a number of terminal AIDS patients have neglible levels of 1,25-D. 18 of 29 patients in a study of AIDS patients had undetectable levels of the metabolite.2) The patients with depressed levels of 1,25-D were characterized by advanced clinical HIV infection, low CD4+ lymphocyte counts, and high serum levels of tumor TNF-alphaA cytokine critical for effective immune surveillance and is required for proper proliferation and function of immune cells. – all indication of more severe forms of the disease.

The exact mechanism by which 1,25-D is downregulated is not entirely known, but it is highly likely that it is caused by pathogens.

Haug et al theorized that TNF-alpha and possibly other cytokinesAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. – which pathogens are known to create3) – inhibit conversion of 25-D into 1,25-D in late-stage cases of HIV/AIDS.4)

A second factor is that HIV disables D-Binding protein (DBP).5) 6) DBP is the precursor for Macrophage Activating Factor (MAF) as it has a key role to play in attracting macrophages to sites of injury. 1,25-D is transported throughout the blood by DBP.

There is no evidence that supplemental vitamin D helps HIV or AIDS patients.

HIV allows opportunistic infections to proliferate

Main article: Co-infections

Pathogens are able spread effectively in an immunocompromised environment. This means it's possible that AIDS patients pick up substantial pathogen loads. It is further possible that it is these Th1 pathogensThe community of bacterial pathogens which cause chronic inflammatory disease - one which almost certainly includes multiple species and bacterial forms., which kill patients. Viral co-infections (including Epstein-Barr virus, Human Herpes Virus 6, etc.) are found in all the diseases the Marshall Protocol treats, but the viruses are not believed to bethe proximate cause of disease.

AIDS patients on the Marshall Protocol

The ARF has no clinical experience with AIDS patients yet. However, we do believe it due time that 'post-HIV wasting disease', and many of the other post-HIV disease are found to be Th1 in pathogenesis.

We would argue that it would make sense for an AIDS patient to strengthen his or her immune response and that the only way to do this is to kill the Th1 pathogens which dysregulate it.

A therapeutic probeA brief trial of the Marshall Protocol to see if it will generate an immunopathological response. The "gold standard" for testing whether a patient is a good candidate for the MP. will confirm the potential efficacy of this treatment.

Notes and comments

<DiseaseHierarchy>

Our recent papers explain that HIV recruits the VDR to sense the Long Terminal Repeat (LTR) on its own genome and allow itself (HIV) to replicate. Once a VDR has been used in this way it becomes no use to the human being who created the VDR in the first place.

The other reason that blood levels of 1,25-D fall in HIV infection is because HIV disables DBP/MAF (D-Binding Protein / Macrophage Activating Factor) which is needed to carry 1,25-D through the bloodstream

..Trevor..

ICAAC: HIV Patients At Risk for Low Vitamin D

By Michael Smith, North American Correspondent, MedPage Today September 12, 2010

MedPage Today Action Points

Explain to HIV-positive patients that additional studies add to the weight of evidence that vitamin D deficiency and bone loss are common, requiring evaluation and treatment. Note that seasonality should be considered when testing for vitamin D levels.

Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Review

BOSTON – People with HIV are at high risk for vitamin D deficiency, according to result of two studies presented here.

In a cross-sectional cohort study of 147 Spanish patients, nearly three-quarters had serum levels of 25-hydroxy vitamin D (25(OH)D) that were below 30 micrograms per liter (µg/L), according to Jose Luis Agud, MD, of Hospital Severo Ochoa in Madrid.

And in a clinical cohort of 395 patients in Lille, France, 90% tested below 30 nanograms per liter (ng/mL) and 41% were below 15 ng/mL, Armelle Pasquet, MD, of the University Hospital Center of Lille, and colleagues, reported at the Interscience Conference on Anti-microbial Agents and Chemotherapy (IAAC) in Boston, Mass.

The Spanish study, in particular, is surprising, Agud told MedPage Today. “We didn't expect vitamin D would be a problem in Spain,” he said, because levels of sunshine are high and the use of sunblock is relatively low. The finding “came to our surprise,” Agud said.

The Spanish study defined vitamin D deficiency as 25(OH)D <20 µg/L. In the French study, vitamin D deficiency was defined as around 15 ng/mL.

The issue is important because vitamin D deficiency is thought to play a role in bone loss in people with HIV, according to Laurent Kaiser, MD, of the University Hospital Geneva, a member of the ICAAC conference program committee who was not part of either study.

Kaiser told MedPage Today that he routinely prescribes vitamin D supplements to his HIV-positive patients, even if they are not deficient.

http://www.medpagetoday.com/tbprint.cfm?tbid=22132

Indeed, a third study here confirmed the risk of bone loss among those with HIV. Researchers led by Anna Bonjoch, MD, PhD, of University Hospital Germans Trias i Pujol in Barcelona, that nearly a third of a cohort of 391 HIV patients had progressive bone loss.

Bonjoch and colleagues found that 12.5% of the cohort progressed from normal to osteopenia, and 15.6% went from osteopenia to osteoporosis. If only the 105 patients with more than five years of follow-up were assessed, they found, 47% had a loss of bone mineral density, with 18% developing osteopenia and 29% osteoporosis.

Analysis of the Spanish cohort, Agud said, turned up some obvious risk factors for deficiency and some that were less obvious.

For instance, he and colleagues found, there was clear seasonality, with higher risk for deficiency in the winter and spring and a lower risk in summer and fall. When spring measurements were compared with those taken in summer, the odds ratio for deficiency was 8.2, with a 95% confidence interval from 3.3 to 10.5, which was significant at P=0.0001.

On the other hand, Agud said, the researchers are at a loss to explain why their analysis showed that people who acquired HIV through heterosexual contact had a higher risk of deficiency – a significant odds ratio of 2.54 – than injection drug users.

They also found that use of the non-nucleoside reverse transcriptase inhibitor nevirapine (Viramune) was associated with a protective effect.

On the other hand, the French study found that use of non-nucleoside reverse transcriptase inhibitors was correlated with lower levels of 25(OH)D – although the correlation did not reach significance for any particular drug, Pasquet told MedPage Today.

Using a cut-off of about 15 ng/mL as their definition of vitamin D deficiency for the French cohort, Pasquet said, 41% of her study population was deficient.

The French study was supported by the ARNS. Pasquet said and her colleagues she had no conflicts.

The Spanish vitamin D study had no external support. The researchers said they had no conflicts.

Bonjoch and colleagues did not report any external support for the study. They said they had no conflicts.

Kaiser said he had no conflicts.

Primary source: Interscience Conference on Antimicrobial Agents and Chemotherapy Source reference: Pasquet A et al. “Prevalence and risk factors for hypovitaminosis D among HIV-infected patients in a French HIV Clinical Cohort” ICAAC 2010; Abstracts H-225.

Additional source: Interscience Conference on Antimicrobial Agents and Chemotherapy Source reference: Cervero M et al. “Prevalence of vitamin D deficiency in HIV infection” ICAAC 2010;

Presentation Abstract

Session: 15-HIV Complications Sunday, Sep 12, 2010, 11:30 AM - 1:30 PM Presentation Title: H-230 - Prevalence of Vitamin D Deficiency in HIV infection Location: Exhibit Hall B1 Poster Board Number: 242 Presentation Number: H-230 Pres. Time: Sunday, Sep 12, 2010, 11:30 AM - 1:30 PM Category: H Keywords: Vitamin D; HIV; HAART Author(s): M. CERVERO, V. ALCÁZAR, C. GARCÍA-LA CALLE, R. SANZ, J. AGUD; Hosp. Severo Ochoa, MADRID, Spain. Financial Disclosures: M. Cervero, None.. V. Alcázar, None.. C. García-La Calle, None.. R. Sanz, None.. J. Agud, None. Abstract: Background: To examine the prevalence and causal factors of vitamin D deficiency among HIV-1 infected patients and specially to assess whether antiretroviral drugs interfere with vitamin D metabolism. Methods: We performed a cross-sectional study of a hospital cohort (n=147) of HIV-1 infected outpatients followed-up by the same physician. Data were collected between January 2008 and January 2010. We draw samples for the measurement of 25(OH)D3, PTHi, serum calcium, serum phosphate, alkaline phosphatase, CD4+ cell count and viral load. Data on age, sex, VIH infection risk group, weight, height, skin color, time since HIV diagnosis, duration and stage of the infection (according to CDC 1983 staging system), as well as duration of typo of antiretroviral therapy (ART). A nutrition specialist of the same hospital performed a survey of sunlight exposition and daily vitamin D intake. We performed bi- and multivariant analysis to identify risk factor related to vitamin D deficiency (25(OH)D <20 μg/L). Results: Median age was 44 years; 67.3% were males and 89,1% caucasians. CD4+ count was < 200 cels/μ in 15,6 %, and 78.7% had a viral load below 30 copies/ml. Median serum 25(OH)D level was 21.1 µg/L (IQR 12,8-28,3) and 47,6% had 25(OH)D < 20 µg/L. Multivariant analisis of predisposing factor to vitamin D deficiency showed increased risk in spring vs. autumn (OR 8.2 [95%CI 3.3-20.25], p=0,0001), heterosexual vs. IDU (OR 2,54 [ 95% CI 1.04-6.16],p=0,04) and increase of BMI (OR 1,19 [1,06-1,34], p=0,003) : Current nevirapine use was protective against development of vitamin D deficiency (OR 0,14 [0,03-0,79], p=0,026). Black race was not a risk factor, but it was underrepresented in our sample. Conclusions: Despite the low latitude of Spain, moderate vitamin D deficiency in HIV infected patients is more prevalent in our cohort than in the cohorts of Switzerland, Netherlands and Boston. It was related to the season (spring) heterosexual risk group and increasing BMI. The use of nevirapine may diminish the risk of vitamin D deficiency.

resentation Abstract Session: 15-HIV Complications Sunday, Sep 12, 2010, 11:30 AM - 1:30 PM Presentation H-230 - Prevalence of Vitamin D Deficiency in HIV Add to Itinerary Print Title: Location: Poster Board Number: Presentation Number: Pres. Time: Category: Keywords: Author(s): Financial Disclosures: infection Exhibit Hall B1 242 H-230 Sunday, Sep 12, 2010, 11:30 AM - 1:30 PM H Vitamin D; HIV; HAART M. CERVERO, V. ALCÁZAR, C. GARCÍA-LA CALLE, R. SANZ, J. AGUD; Hosp. Severo Ochoa, MADRID, Spain. M. Cervero, None.. V. Alcázar, None.. C. García-La Calle, None.. R. Sanz, None.. J. Agud, None. Abstract: Background: To examine the prevalence and causal factors of vitamin D deficiency among HIV-1 infected patients and specially to assess whether antiretroviral drugs interfere with vitamin D metabolism. Methods: We performed a cross- sectional study of a hospital cohort (n=147) of HIV-1 infected outpatients followed-up by the same physician. Data were collected between January 2008 and January 2010. We draw samples for the measurement of 25(OH)D3, PTHi, serum calcium, serum phosphate, alkaline phosphatase, CD4+ cell count and viral load. Data on age, sex, VIH infection risk group, weight, height, skin color, time since HIV diagnosis, duration and stage of the infection (according to CDC 1983 staging system), as well as duration of typo of antiretroviral therapy (ART). A nutrition specialist of the same hospital performed a survey of sunlight exposition and daily vitamin D intake. We performed bi- and multivariant analysis to identify risk factor related to vitamin D deficiency (25(OH)D <20 μg/L). Results: Median age was 44 years; 67.3% were males and 89,1% caucasians. CD4+ count was < 200 cels/μ in 15,6 %, and 78.7% had a viral load below 30 copies/ml. Median serum 25(OH)D level was 21.1 !g/L (IQR 12,8-28,3) and 47,6% had 25(OH)D < 20 !g/L. Multivariant analisis of predisposing factor to vitamin D deficiency showed increased risk in spring vs. autumn (OR 8.2 [95%CI 3.3-20.25], p=0,0001), heterosexual vs. IDU (OR 2,54 [ 95% CI 1.04-6.16],p=0,04) and increase of BMI (OR 1,19 [1,06-1,34], p=0,003) : Current nevirapine use was protective against development of vitamin D deficiency (OR 0,14 [0,03-0,79], p=0,026). Black race was not a risk factor, but it was underrepresented in our sample. Conclusions: Despite the low latitude of Spain, moderate vitamin D deficiency in HIV infected patients is more prevalent in our cohort than in the cohorts of Switzerland, Netherlands and Boston. It was related to the season (spring) heterosexual risk group and increasing BMI. The use of nevirapine may diminish the risk of vitamin D deficiency.

http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=92475&Ausgabe=231692&ProduktNr=223834

References

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