File Name: hiv aids and vitamin studies in kenya .zip
- Vitamin D Deficiency and Its Health Consequences in Africa
- Malnutrition in HIV/AIDS: Aetiopathogenesis
- Influence of Vitamin D in HIV Infection
Africa is heterogeneous in latitude, geography, climate, food availability, religious and cultural practices, and skin pigmentation. It is expected, therefore, that prevalence of vitamin D deficiency varies widely, in line with influences on skin exposure to UVB sunshine.
Box Eldoret, Kenya. Nutritional status is an important determinant of HIV outcomes. Prospective cohort study. Main Outcome Measures.
Vitamin D Deficiency and Its Health Consequences in Africa
In HIV-infected persons, low serum concentrations of vitamins and minerals, termed micronutrients, are associated with an increased risk of HIV disease progression and mortality. The provision of simple, inexpensive micronutrient supplements as an adjunct to HAART may have several cellular and clinical benefits, such as a reduction in mitochondrial toxicity and oxidative stress and an improvement in immune reconstitution.
We reviewed observational and trial evidence on micronutrients in HIV-positive persons receiving HAART to summarize the current literature and suggest future research priorities. A small number of observational studies have suggested that some, but not all, micronutrients may become replete after HAART initiation, and few intervention studies have found that certain micronutrients may be a beneficial adjunct to HAART.
However, most of these studies had some major limitations, including a small sample size, a short duration of follow-up, a lack of adjustment for inflammatory markers, and an inadequate assessment of HIV-related outcomes.
Because micronutrient supplementation may cause harm, randomized placebo-controlled trials are needed. Access has been gradually increasing in low- and middle-income countries, and leaders of the G8 Summit pledged to provide global access to HIV medications by The transition to greater access to HIV medications will shift the research priorities related to vitamins and minerals, termed micronutrients, in HIV-infected persons.
Micronutrient deficiencies, which are commonly observed with advanced HIV disease, have been associated with higher risks of HIV disease progression and mortality 2 , 3. Body weight loss and wasting are also features of HIV disease progression 4 and are strong independent predictors of HIV-related morbidity and mortality 5 — 9. Micronutrient deficiencies, body weight loss, and wasting in advanced HIV disease are caused by a similar combination of decreased food intake, gastrointestinal malabsorption, increased metabolic demand, and body redistribution 10 , HAART restores immunologic function 13 , but does not eliminate weight loss and wasting 14 , 15 , which continue to be strong independent predictors of mortality Because low micronutrient concentrations are caused by similar mechanisms and several micronutrient concentrations are lower among patients with HIV wasting syndrome 17 , micronutrient deficiencies may also persist in the era of HAART.
Although some researchers have recently called for micronutrient supplements as an adjunct therapy to HAART 19 , 24 , no review articles, to our knowledge, have summarized studies describing micronutrient concentrations and micronutrient intervention trials in HIV-positive persons receiving HAART. We reviewed published studies of micronutrients and HAART to summarize the literature and suggest future research priorities. Micronutrients are essential for maintaining proper immunologic function 25 , Vitamin A deficiency reduces a lymphocyte response 27 , vitamin C deficiency depresses a cell-mediated immune response 28 , and vitamin E deficiency impairs T cell—mediated function and lymphocyte proliferation Among the B vitamins, riboflavin deficiency impairs the generation of a humoral antibody response, vitamin B-6 deficiency reduces lymphocyte maturation and diminishes antibody production, and vitamin B deficiency impairs neutrophil function Among certain minerals, folic acid deficiency depresses the cell-mediated immunity response 31 , zinc deficiency decreases lymphocyte concentrations 32 , copper deficiency reduces the cytokine response 33 , and selenium is needed for proper functioning of neutrophils and T lymphocytes Compared with HIV-negative person, HIV-infected persons have lower serum concentrations of several micronutrients and more commonly have micronutrient deficiencies 35 — Basic nutritional and metabolic disturbances that lead to weight loss and wasting in HIV-infected persons may represent an adaptive response to an inflammatory state 66 — Proinflammatory cytokine concentrations are significantly higher in HIV-positive persons than in HIV-negative persons Elevated cytokines may also contribute to the chronic oxidative stress observed in HIV-positive persons 73 , which could lead to HIV disease progression through impairment of immune function 74 , enhancement of HIV replication 73 , or both.
Nutritional and metabolic disturbances can also lead to altered acute phase response proteins in response to acute or chronic inflammation, which have been observed in persons with advanced HIV disease 75 , Changes in acute phase response proteins, mainly decreased albumin and elevated C-reactive protein concentrations, have been shown to be associated with low serum concentrations of several micronutrients in HIV-negative persons 77 — 87 and with low serum concentrations of vitamin A and selenium in HIV-positive persons not receiving HAART 88 , Although albumin may be a better measure of nutritional status than inflammation 92 , these studies suggest that micronutrient deficiencies that persist after HAART initiation could be due to an inflammatory response.
Although the authors did not adjust the analyses by plasma viral load or CD4 cell count, they reported no significant differences in vitamin concentrations between 3 CD4 cell count categories. Therefore, confounding by CD4 cell count would have been unlikely. Given the nature of the study design and lack of adjustment for different historical factors, these results should be interpreted with caution. Mean vitamin concentrations adjusted for dietary intake, supplement use, injection drug use, sex, cigarette smoking, and alcohol consumption.
Mean vitamin concentrations adjusted for supplement use, injection drug use, sex, cigarette smoking, and alcohol consumption. Median vitamin concentrations represent average vitamin B concentrations at the baseline of each patient-time interval. These findings suggest that antioxidant capacity could be high in adults receiving HAART, irrespective of selenium concentrations.
We identified 2 longitudinal observational studies that assessed micronutrient concentrations in HIV-positive persons before and after HAART initiation. The investigators noted significant increases in fasting glucose and insulin resistance, a significant decrease in waist-to-hip ratio, a trend for a decrease in LDL, and no significant changes in serum lactate, body fat, lean body mass, CD4 cell count, or plasma viral load.
These investigators suggested that these changes may be the result of the natural history of insulin resistance in lipoatrophy. Another nonrandomized intervention study assessed the effects of either a low-dose or high-dose antioxidant regimen mainly vitamins A, C, and E and selenium for 12 wk on antioxidant defenses, oxidative stress, and plasma viral load Of the 48 HIV-positive adults who completed the study, of whom 32 were receiving HAART, antioxidant supplements significantly increased antioxidant defenses but had no significant effect on oxidative stress or plasma viral load.
No significant differences were observed between those supplemented with low-dose and those supplemented with high-dose antioxidants, and the authors reported no differences between those receiving and not receiving HAART. Periods of calcium supplementation had no significant clinical improvements in the diarrhea score.
The authors reported no significant differences in the CD4 count, ratio of CD4 to CD8, and plasma viral load between the 2 groups, but a greater increase in lymphocyte viability was observed in the vitamin E—supplemented group Another placebo-controlled trial assessed the effect of a daily supplement of vitamins A, C, and E for 6 mo on antioxidant defenses, oxidative stress, and CD4 cell count in 30 HIV-infected adults At baseline, concentrations of vitamins A, C, and E were significantly lower among the trial cohort compared with a small group of HIV-negative healthy volunteers.
At follow-up, concentrations of vitamins A, C, and E had been restored in the supplemented group, but not in the placebo group. Furthermore, the supplemented group had significantly greater antioxidant defenses and less oxidative stress than did the placebo group.
A placebo-controlled trial examined the effect of 2 y of selenium supplementation on CD4 cell counts and hospital admissions in HIV-positive injection-drug users, 85 of whom were receiving HAART The 2 groups were similar at baseline, with the exception that fewer subjects receiving selenium were not taking any HIV medications.
In addition, the supplemented group had fewer hospitalizations for opportunistic infection and other HIV-related conditions than did the placebo group. However, hospitalizations were fewer among the participants receiving HAART than in those not taking any HIV medications, which were not evenly distributed at baseline.
In multivariate analyses, adjusted for HAART treatment, other HIV medications, age, baseline CD4 count, baseline viral load, and selenium supplementation were significantly associated with fewer hospitalizations. Finally, a recent randomized controlled trial conducted in 40 HIV-infected adults found that comprehensive micronutrient supplementation for 12 wk significantly increased the CD4 T cell count and had no significant effect on plasma viral load compared with the placebo group In addition, the investigators found that micronutrient supplementation had no significant effects on fasting glucose, insulin, lipids, venous lactates, serum creatinine, alanine aminotransferase, total bilirubin, or alkaline phosphatase.
A summary of our review of micronutrient intervention studies in HIV-infected persons receiving HAART suggests that micronutrient supplementation has shown mixed beneficial effects on immunologic status, plasma viral load, and clinical outcomes.
Both intervention studies with antioxidants found increased oxidative defenses, but only one of those studies found decreased oxidative stress, and neither study found a reduced plasma viral load.
Two intervention studies that examined micronutrient interventions for HAART-related side effects were small and found no significant improvements. One small recent intervention study found significant improvements in CD4 count but not in plasma viral load. However, intervention studies have been few in number and have individually had major limitations, most commonly a small sample size and a short intervention period. Anemia is more common and more severe with advanced HIV disease progression , and studies disagree on whether this is principally due to iron-deficiency anemia or to anemia of chronic disease — Several longitudinal studies have reported either a significant increase in hemoglobin concentration or a significant decrease in clinical anemia 1 y after HIV-positive persons began HAART — In a multivariate analysis in which BMI, opportunistic infections, and sex were adjusted for, mean hemoglobin concentrations increased significantly by 0.
In another multivariate analysis, adjusted for CD4 cell count, plasma viral load, and anemia treatments, HAART was strongly associated with not becoming anemic during the follow-up period Although mean iron concentrations had increased from At follow-up, iron concentrations were not significantly different between those receiving and those not receiving HAART. Although the results are based on only one small study, they provide little insight on whether improvements in anemia after HAART initiation are primarily related to iron repletion.
Although HIV-associated anemia is caused by several factors, several intervention trials have found beneficial effects of epoetin-alfa on anemia. An overview of 4 randomized placebo-controlled trials, which included HIV-infected anemic participants taking zidovudine, also found that epoetin-alfa reduced the number of required blood transfusions Although HAART has been shown to be associated with a decreased prevalence of opportunistic gastrointestinal diseases and incidence of malnutrition , gastrointestinal infections and severe gastroenteritis, which alter micronutrient absorption, may persist after HAART initiation 11 , Several HIV medications, particularly NRTIs, can inhibit the replication of mitochondrial DNA and cause vomiting and diarrhea that can reduce the absorption or increase the losses of several micronutrients , Mitochondrial toxicity may also increase the production of reactive oxygen species, resulting in oxidative damage, which can lead to lactic acidosis Patients initiating HAART often experience a gain in central adiposity and lean mass over the first 24 wk and may develop glucose intolerance, insulin resistance, hyperlipidemia, and peripheral lipoatrophy after 6 mo — HIV medications may also have a direct effect on the synthesis and metabolism of certain micronutrients.
Three PIs—ritonavir, indinavir, and saquinavir—have been shown in cell and tissue cultures to significantly increase retinal dehydrogenase activity, an enzyme responsible for the production of all-trans retinoic acid, a precursor of vitamin A Furthermore, indinavir also induced retinal dehydrogenase gene expression The restoration of depleted micronutrients through supplementation may have several cellular and clinical benefits in HIV-positive persons receiving HAART.
In a randomized placebo-controlled trial of 75 HIV-positive persons taking zidovudine, participants receiving daily folinic acid 15 mg and monthly vitamin B 1 mg had no significant reductions in hematologic toxicity or myelotoxicity after 12 mo However, HIV-infected patients with lower baseline concentrations of vitamin B had increased incidences of anemia, leucopenia, and neutropenia during the study period First, a study of HIV-positive adults receiving HAART found that a greater total intake of vitamin E was associated with fewer outcomes of HAART-associated metabolic complications, including body fat redistribution, dyslipidemia, and insulin resistance, which the investigators hypothesized may have been due to changes in the ratio of plasma reduced to oxidized glutathione and oxygen free radicals Second, thiamine and riboflavin , which are important for normal mitochondrial function, have both been shown to reduce NRTI-associated lactic acidosis.
In addition, regular vitamin E supplementation has also been associated with significantly lower serum lactate concentrations in 30 HIV-positive persons receiving HAART Therefore, several micronutrients may play a role in reducing mitochondrial dysfunction, oxidative stress, and metabolic complications, which are commonly experienced by HIV-positive persons receiving HAART. Micronutrient supplements may not always be beneficial in HIV-infected persons.
In asymptomatic HIV-positive men, greater zinc intakes from foods and supplements has been shown to be associated with faster HIV disease progression and mortality in a clear dose-response relation 45 , Randomized trials have shown that maternal vitamin A supplements significantly increase the risk of mother-to-child transmission of HIV and can increase mortality in some children born to HIV-positive mothers Other randomized trials have shown that supplementation with vitamin A and with a multivitamin containing selenium can cause increased viral shedding in the female genital tract.
Given these previous trials, one should not presume that taking micronutrients are always beneficial, and proposed micronutrient interventions should be scrutinized by well-designed, randomized, placebo-controlled trials. Micronutrient supplements can also have adverse effects on cellular mechanisms in HIV-positive persons.
Two patients were reported to have an increase in plasma viral load after the initiation of iron supplementation for iron-deficiency anemia Micronutrient interventions have also been shown to alter the bioavailability, metabolism, and pharmacokinetics of certain HIV medications. Furthermore, St John's wort and garlic supplements, both popular herbal treatments, have also been shown to significantly reduce plasma concentrations of indinavir and saquinavir, respectively , These studies raise concerns about the possibility of micronutrient and herbal supplementation leading to increased toxicity or viral resistance in instances where drug metabolism or clearance is enhanced.
Of the 2 identified longitudinal studies, both of which were small, d of HAART did not significantly increase concentrations of vitamin B-6, vitamin B, or folate in 17 HIV-positive adults, and up to 3 y of HAART did not significantly increase concentrations of selenium, iron, zinc, or copper in 23 HIV-positive users of injection drugs.
Another longitudinal study, which was not included in the review because it was conducted between and and did not define treatment regimens, found adjusted concentrations of serum vitamin B, but not of serum folate, increased significantly 6 mo after HIV medications were initiated in 38 HIV-positive adults However, none of these observational studies adjusted micronutrient concentrations by inflammatory markers, which could alter serum concentrations of several micronutrients.
Although we attempted to identify all published studies relevant to micronutrients and HAART, we may not have captured all relevant articles in this review. In addition, the results presented from these published articles may be subject to a publication bias, which typically favors studies reporting significant findings. In addition, the observational and interventional studies presented in this review are subject to their own biases and limitations, and most were limited by small sample sizes.
Despite these limitations, this review helps highlight some research gaps and generates suggestions for future research related to micronutrient supplementation in HIV-positive persons receiving HAART. First, because studies have persistently described high concentrations of inflammatory markers after HAART initiation , , a longitudinal description of changes in micronutrient concentrations after HAART initiation, with adjustments for acute inflammatory markers, especially C-reactive protein, would be valuable.
Second, because no trials have assessed the effect of micronutrient supplements on clinical disease progression or mortality in HIV-positive persons receiving HAART, large randomized placebo-controlled trials should be conducted in HIV-positive persons receiving HAART to determine the effect on clinical, rather than laboratory, HIV-related outcomes and side effects of particular HIV medications.
Malnutrition in HIV/AIDS: Aetiopathogenesis
Environmental enteric dysfunction has now been identified to play a significant role in HIV-malnutrition. Food insecurity is bidirectionally associated with aggravation and perpetuation of HIV infection. Increasingly, drugs used in antiretroviral therapy have been recognised to lead malnutrition in many ways. Both HIV and malnutrition are most prevalent in the poorest areas of the world, and there is a convergence of etiological factors. Malnutrition depresses every aspect of immune function. Deficiency of key micronutrients like iron, folic acid, zinc, selenium and vitamins A, C and D also adversely affects immune function. Recent research has led to a greater understanding of these mechanisms.
Malnutrition is common among HIV-infected individuals and is often accompanied by low serum levels of micronutrients. Vitamin B deficiency has been associated with various factors including faster HIV disease progression and CD4 depletion in resource-rich settings. Logistic regression was used to determine factors associated with sub-optimal vitamin B Twenty-one of Irritable mood was observed more among individuals with sub-optimal vitamin B levels OR 2. Increasing MCV was associated with decreasing serum B category; Compared to normal B, individuals with vitamin B deficiency had a longer known duration of HIV infection:
Influence of Vitamin D in HIV Infection
Волоча Сьюзан за собой, он использовал ее как живой щит. Преодолев треть ступенек, он почувствовал какое-то движение у подножия лестницы. Стратмор что-то задумал. - И не пытайтесь, коммандер, - прошипел .
Да будь они прокляты, эти криптографы. Ничего не понимают в системах безопасности. Присяга, которую Чатрукьян принимал, поступая на службу в АНБ, стала непроизвольно прокручиваться в его голове. Он поклялся применять все свои знания, весь опыт, всю интуицию для защиты компьютеров агентства, стоивших не один миллион долларов.
Эта тактика себя оправдала. Хотя в последнее мгновение Беккер увернулся, Халохот сумел все же его зацепить. Он понимал, что пуля лишь слегка оцарапала жертву, не причинив существенного ущерба, тем не менее она сделала свое. Контакт был установлен. Жертва ощутила прикосновение смерти, и началась совершенно иная игра. Беккер мчался, не видя ничего вокруг, постоянно сворачивал, избегая прямых участков.
Сьюзан, глядя на мультимедийный клип, понимала, что все кончено. Она следила за смертью Танкадо - в который уже. Он хотел говорить, но слова застревали у него в горле. Он протягивал свою изуродованную руку… пытаясь что-то сообщить.
Просто мне приходится быть крайне осторожным. В тридцати футах от них, скрытый за стеклом односторонней видимости Грег Хейл стоял у терминала Сьюзан. Черный экран. Хейл бросил взгляд на коммандера и Сьюзан, затем достал из кармана бумажник, извлек из него крохотную каталожную карточку и прочитал то, что было на ней написано.