Severely malnourished patients entering ART
In poor countries with fee-for-service medical services and high stigma, it is common for HIV status to be unknown until PLHIVs are admitted to hospital with serious illness, often of long duration. Fear of stigma leads many, particularly men, to avoid HIV and TB testing and treatment until their situation is already extreme. Such late presentation patients may arrive with BMIs down to 13, at risk of organ failure. For such severely wasted patients entering highly active antiretroviral therapy, access to competent nutrition rehabilitation “is an immediate matter of life and death” (Paton 2006). Management of malnutrition-associated dehydration is urgent, with enteral feeding by naso-gastric tube or parenteral feeding (by IV drip) indicated until the patient can eat (Ockenga 2006). Selenium should be included in parenteral mixes, as deficiency causes serious metabolic problems (Gramm 1995). Intensive care will often be required for survival of HIV-positive children presenting to NRUs with severe acute malnutrition whether or not they commence ART, including therapeutic feeding.
TB/HIV coinfected patients
Malnutrition is well known to predispose people to develop active TB. Malnutrition and wasting are particular issues for patients coinfected with HIV and TB. Malnourishment further weakens the cell-mediated immune response in people with HIV, increasing the risk that latent TB infection will become active disease. HIV, TB and malnutrition are mutually reinforcing in their effects on energy expenditure, malabsorption, micronutrient deficiency, and oxidative stress (van Lettow 2003, Niyongabo 1999). Niyongabo et al examined nutritional status of HIV-positive and HIV-negative hospitalized TB patients in Burundi, finding lower body weight, fat mass, and fat-free mass in the co-infected cases.
Patients with active TB are typically wasted (van Lettow 2004, Harries 1988, Paton 2004), with weight loss seen in almost every patient at TB diagnosis in resource-poor settings (Schwenk 2000). TB affects protein metabolism and nutritional status through multiple mechanisms, including raising resting metabolic rate and reducing appetite (Dye 2006). TB treatment usually improves nutritional status, but fat mass may be preferentially restored with little rebuilding of muscle tissue (Schwenk 2004). Malnutrition may trigger relapse of treated TB (Khan 2006).
Patients with active TB suffer depressed blood concentrations of antioxidant vitamins A (Mugusi 2003, Ramachandran 2004, van Lettow 2005), C (Hemila 1999, Bakaev 2004) and E (Bakaev 2004, van Lettow 2005), zinc (Kassu 2006, van Lettow 2005), iron (Kassu 2006), and selenium (Kassu 2006, van Lettow 2005) compared with healthy controls, partly due to the immune system response to infection, which raises oxidative stress, lowering antioxidant capacity (Madebo 2003, Vijayamalini 2004). Anaemia, due to coughing blood, decreased red blood cell production and inadequate intake is common in pulmonary TB patients and even more so among the TB/HIV co-infected (van Lettow 2005, Das 2003), and needs to be considered when choosing a first-line ART regimen (AZT may exacerbate pre-existing anaemia).
USAID recommends micronutrient supplementation for TB patients, since some evidence that daily micronutrient supplementation may benefit those with deficiencies, especially during the early months of anti-TB therapy (Papathakis 2008) (though little systematic data is available to guide interventions). High-energy protein supplements (600-900kcal/day, 25-37.5gm protein/day) initiated at commencement of anti-TB drugs may significantly improve lean body weight and physical function (Chandra 2004, Paton 2004), though no specific recommendations have yet been internationally agreed (Papathakis 2008).
While evidence of the impact of food support on TB patients’ nutritional status, quality of life, treatment adherence, and outcome is mainly anecdotal, it appears to be valuable in rehabilitation. Food support is often used to encourage TB patients to complete the full duration of their treatment as well as improving nutrition status, maximising cure rates and minimising antibiotic resistance. Food assistance may also influence early case detection, but according to USAID “the cost to programs of providing food support may be considerable” (Papathakis 2008).
TB medications affect nutritional status: isoniazid increases excretion of vitamin B6, causing peripheral neuropathy (Visser 2004), while rifampicin alters vitamin D metabolism and so may weaken bones (Roth 2004). WHO/WFP recommends that vitamin B6 and vitamin D supplementation should be considered for PLHIV during TB treatment. Given the elevated risk of peripheral neuropathy in people with HIV, especially those also receiving d4T-based ART, vitamin B6 supplementation is arguably essential in any HIV-positive person receiving isoniazid.
Paton et al found that patients entering TB treatment randomised to a high energy-protein supplement (600- 900kcal/d, 25-37.5gm protein/d) for six weeks showed significant increases in body weight, lean mass, fat mass and grip strength compared to controls (Paton 2004). Since in the first month of TB treatment, moderate to severe under-nutrition is associated with increased risk of death (Zachariah 2002), Paton et al suggest that swift nutritional rehabilitation for wasted TB patients, as for HIV patients, may have significant impact on mortality.
There is evidence of increased risk of malnutrition and resulting mortality among TB/HIV co-infected children (Palme 2002, Hesseling 2005, Soeters 2005).
Pregnant and lactating women
Pregnant women require around 285 additional calories each day, and breastfeeding women at least 500 extra calories (WHO 2000). More research is needed concerning the interaction of ART with nutritional status during pregnancy and lactation (Friis 2005), but one study found that vertical transmission approximately doubled in HIV+ women who lost weight during their pregnancy (Villamor 2005a. Pregnant women may also be at increased risk of developing active TB. For instance, (Venkatesh 2005).
Improved maternal micronutrient status may reduce vertical transmission of HIV by enhancing maternal immune function and reducing viral load (Nduati 1995, Fawzi 2001). High-dose vitamin supplements have been shown to increase CD4 (Fawzi 1998, French 1998, Swiss HIV Pregnancy Cohort 1997), Multivitamins may decrease the risk of secondary maternal infections during pregnancy and result in improved weight gain; lower levels of anaemia may diminish maternal birth complications. In addition, provision of folic acid and vitamin B12 which may assist T-cell production as well as benefit the foetus, as these nutrients function in development and proliferation of cells (Fawzi 1998, Villamor 2002).
But not all vitamin supplementation studies have found such beneficial effects. In a study of 357 HIV-positive Kenyan women, high dose multiple vitamins with selenium versus placebo were used to investigate the effect of micronutrient supplementation on cervical and vaginal shedding of HIV-infected cells. CD4+ and CD8 lymphocyte counts increased, while viral load was unchanged, but vaginal HIV shedding was significantly higher in those supplemented than in those receiving placebo (McClelland 2004). Meanwhile, although vitamin A supplementation in HIV-infected women can reduce maternal mortality (West 1999), raise birth weights and improve infant growth (Villamor 2002, Villamor 2005b), it may increase mother-to-child transmission. In a Tanzanian randomised controlled trial, daily vitamin A increased mother-to-child transmission (Fawzi 2002). According to WHO, single high-dose vitamin A supplements to HIV-infected mothers and/or their infants postpartum have not affected vertical transmission or overall mortality up to 24 months (Humphrey 2006). Research is needed on protocols to allow vitamin A-deficient PMTCT clients to benefit from provision of this important antioxidant without increasing vertical transmission.
Anaemia can increase vertical transmission (Iliff 2005). A survey by UNICEF and the Government of Kenya found that 49% of new Kenyan mothers had iron deficiency anaemia, with 73% prevalence rates among children under five. Anaemia was associated with vitamin A and zinc deficiencies, and with malaria and hookworm (UNICEF (2002).
Similarly, 83% of 1064 HIV-positive pregnant women enrolled in a Tanzanian supplementation study were anaemic, with mean CD4+ cell count, haemoglobin and serum retinol levels independently associated. Women with BMI less than 19 were at least three times more likely to have severe anaemia than were those with BMI exceeding 24. Folate deficiency, assessed by the presence of macrocytic cells, was found in only 5% of the women (Antelman 2000). Standard iron-folic acid supplementation among pregnant women is helpful for PMTCT patients, but supplementation of other micronutrients may also improve outcomes (Friis 2005).
In the most malnourished HIV-infected women with the weakest immunity, daily supplementation with high-dose vitamins B, C and E during pregnancy and lactation reduced mother-to-child HIV transmission in Tanzania (Chatterjee 2007). There was no significant effect on vertical transmission from other women, but with supplementation over several years, their own disease progression slowed, with effects on viral load and CD4 counts observed. These results need to be confirmed in other contexts.
Both HIV-positive and HIV-positive children with an HIV-infected parent have been shown to be at elevated risk of malnutrition, possibly due to heightened susceptibility to household food insecurity (Chatterjee 2007). Children born to HIV-infected mothers are at high risk of low birth-weight and stunting (Bailey 1999). Malnutrition has the greatest impact during gestation and the first two years of life, with some damage irreversible (Martorell 1994).
WHO recommends early nutrition support as an integral part of care of HIV-infected infants and children, including ensuring a daily intake of micronutrients equivalent to the recommended daily allowance, ideally from locally available and affordable foods (WHO/WFP 2008).
Exclusive breastfeeding is recommended for HIV-infected women up to 6 months (Coovadia 2007, WHO 2003, Kourtis 2006) unless earlier replacement feeding is acceptable, feasible, affordable, sustainable, and safe. At 6 months, rapid weaning over 2-21 days is recommended (Kourtis 2006, WHO 2003, WHO 2005a) to avoid the enhanced risks associated with mixed feeding (Newell 2007) (however, subsequent studies have reported that weaning too abruptly may not improve HIV-free survival). Breastfeeding should only stop once a nutritionally adequate and safe diet without breast milk can be provided. As complementary foods, WHO recommends boiled full-cream milk or yoghurt, other animal products, fruits and vegetables, and fortified foods or a micronutrient supplement. WHO states that if adequate food (600 kcal/day) is not available at 6 months, mixed feeding is needed to avoid malnutrition (Newell 2007). After six months, any liquids given should be fed by cup rather than bottle (WHO 2003), because bottles are hard to clean.
HIV-positive mothers must decide whether to breastfeed or formula-feed, balancing the risk of transmitting the virus to their children against possible health risks associated with replacement feeding. A further consideration is that the social and economic consequences of disclosing HIV-positive status by not breastfeeding where that is customary could pose risks to the infant outweighing the risk of vertical transmission. These calculations may change when DNA PCR testing for HIV in the infants of infected mothers becomes routine in resource-poor settings soon after birth.
In many HIV-affected communities, the diet of a typical child may be wholly inadequate, containing of little more than starchy staples such as cassava or polished rice. An MSF doctor said of her nutrition project in Niger “eating millet porridge every day is the equivalent of living off bread and water. With luck, toddlers here might have milk once or twice a week” (MSF 2008).
Dietary intake of HIV-infected infants and children should be 10% higher than that of uninfected peers, and intake should increase by 20–30% while suffering or recovering from acute infection. Children’s bodies respond to under-nutrition initially by retarding growth (Arpadi 2005), thus WHO/WFP recommend that any child who is losing weight, regardless of HIV status, should increase intake by 50-100% to permit catch-up growth (WHO 2003).
Both wasting and stunting are common among children living with HIV (Doherty 2006). Fifty-nine per cent of the first 145 HIV-infected children to receive antiretroviral therapy in a Botswana-based study were severely wasted, with 75% severely stunted (Anabwani 2003). Height for age is an important predictor of survival in HIV-infected children (Benjamin 2003, Carey 1998, Chantry 2003). Opportunistic infections may further check growth (Doherty 2006), particularly TB (and children with HIV are at five times the risk of active TB (Datta 2001).
A 10-country meta-analysis showed that severe wasting in HIV-infected children significantly increased the risk of mortality (3Cs4kids 2008). A Malawian study found that normal weight children were half as likely to die in the first three months of ART as those with mild malnutrition, and one-sixth as likely to die compared with those with severe malnutrition (WHO/WFP 2008). WHO recommends that severely malnourished children who are eligible for ART be medically stabilised before commencing treatment. Antiretroviral therapy can assist children in gaining weight; feeding programmes without ART can help them to regain weight, though more slowly than seronegative children (Diop 2003).
Active case-finding for children with HIV in feeding centre intakes could be productive in high-prevalence countries affected by famine. In a Malawian cohort study aimed at validating current WHO malnutrition guidelines for use with HIV-positive children, 17% of 454 children whose status was known were seropositive. 35% of them died, with half of deaths before day 10 of treatment, and 16% of deaths after return home. Across the sample, CD4 percentages were available for 374 children: 40% of children with a CD4 percentage below 20 died, compared with 15% of those with a CD4 percentage above 20. Fifty-seven per cent of children who showed severe acute malnutrition also had a CD4 percentage below 15. Sixty-nine per cent of the HIV-positive children met criteria for ART, but none were receiving it; 38% of them died in the nutrition rehabilitation unit (AAH 2007).