The study aims were to assess whether a CTC programme can be used as an entry point for HIV services, including HIV testing and treatment of malnutrition in HIV-positive children, and to compare outcomes of HIV-positive and HIV-negative children within the programme. More than half of the HIV-infected children in the PC (59.1%) recovered to a satisfactory nutritional status using CTC protocols, suggesting that SAM can be managed in the community for many HIV-infected children. Furthermore, about two-thirds of the infected children identified after discharge were still adequately nourished. This nutritional recovery occurred without use of antiretroviral therapy (ART), suggesting that severe malnutrition was primarily the result of semi-starvation among recovering study children. These findings are different from those normally observed in developed and middle income countries where severe malnutrition in HIV-positive children is typically caused by HIV-related metabolic disturbances, which do not improve without ART . Indeed, the poor response to nutritional intervention of cachexia, a form of malnutrition that is primarily due to chronic systemic inflammation is a well-known phenomenon [43, 44].
The 59.1% recovery rate for HIV-infected children observed in the PC arm of our study includes deaths in both the inpatient-based stabilisation phase and the outpatient-based recovery phase of care. This figure is similar to the 56% recovery rate reported in a study in southern Malawi where RUTF was used for Home Therapy (HT) in the recovery phase of care, after patients had been discharged from a hospital Nutrition Rehabilitation Unit (NRU) . As mortality amongst severely malnourished HIV-positive children is usually highest during the initial phase of treatment and may exceed 30% , the results from our study are encouraging.
It is possible that our improved recovery rates arise from the decentralised nature of the CTC model of care that is designed to remove barriers to access and promote early presentation before serious complications develop. However, the numbers of HIV subjects in our PC are small and these findings need to be confirmed by larger studies. The results of the present study are also encouraging when compared with the 3-month mortality rate of 42.9% among severely wasted (WFH < 70%) children started on ART, recently reported in Malawi . Mortality in this group was > 10-fold higher than among children starting on ART who were not acutely malnourished (WFH > 80%) .
As observed in other nutritional studies carried out in Malawi, the HIV-positive children in our cohorts recovered more slowly than the HIV-negative children [18, 45]. The possible reasons for slower weight gain include reduced intake due to poor appetite, nutrient malabsorption, increased incidence of infections that were unresponsive to the broad-spectrum antibiotics used, and increased nutrient requirements due to HIV . Despite the possibility of reduced appetite especially at the beginning of treatment, we believe that HIV-positive children may need more RUTF than HIV-negative children to achieve similar growth rates and improvements in other nutritional indices. Increasing the amount of daily energy offered to HIV infected children may improve their weight gain and reduce the length of stay in the program, and further testing of this hypothesis is needed. Continued nutritional surveillance and supplementation after discharge may also help HIV-infected children to remain well-nourished. Reducing recovery time and subsequent length and cost of program participation will reduce default rates, which occurred, on average, after 56 days by families with all HIV-positive children but at 70 days for those who finally defaulted. Similarly, adapting CTC routine antibiotic treatment to the epidemiology of HIV-associated infections and inclusion of routine prophylactic cotrimoxazole for HIV-positive children, as currently recommended by WHO, may improve recovery in this group [1, 48].
The low relapse rates following CTC is in contrast to NRU and other outpatient SAM treatment programmes where morbidity and mortality after discharge are high [49–51]. Although survival bias cannot be ruled out as an explanation for this finding, it is possible that the CTC design, which uses community mobilization and referral for early identification and treatment of SAM also improves long-term recovery compared to hospital-based treatment programmes. SAM is a progressive condition and prognosis is directly associated with the lead time to presentation and treatment. Initiating nutritional intervention as soon as SAM presents may be especially important for HIV-infected and exposed children.
The high VCT uptake for adults and children, the low HIV-prevalence amongst SAM children, and the low nutritional relapse rate amongst surviving HIV-positive and uninfected children over a year after discharge are all noteworthy in our study. The high VCT uptake is comparable to that observed recently in some NRUs in Malawi  but contrasts with anecdotal reports of reluctance to come forward for HIV testing offered by clinics and therapeutic feeding programmes. We believe that the "opt-out" approach used in this study, with HIV testing offered to everyone with the right to refuse rather than the standard "opt-in" approach where people have to specifically request HIV testing, contributed to the high uptake seen here [11, 52, 53]. We also believe that offering testing through a programme such as CTC that is well established in the community improves trust and reduces the fear of stigmatization. Caregivers were informed about the opportunity for HIV testing one week prior to travelling to the health centre and no substantial compensation was offered, ruling out the likelihood of coercion in the RC. The high uptake observed here suggests that CTC is a potentially innovative way to increase access to and coverage of HIV testing, particularly in rural areas . It is important to note however that CTC would have to be combined with other community based HIV testing and counselling approaches like the home based and mobile VCT in order to obtain good coverage; in prior studies we observed that only 16% of HIV-affected households has a malnourished child treated in the CTC programme in the past 18 months [9, 55, 56].
There are a number of factors that are likely to have contributed to the low prevalence of HIV amongst severely malnourished children in this study. Chronic food insecurity, frequent common childhood illnesses, poor access to modern health care and suboptimal complementary feeding practices all cause SAM in the absence of HIV in Malawi [57–59]. The decentralised nature and the high coverage rates obtained by CTC programmes means that a higher proportion of admissions live in remote rural areas far from towns and main roads  in contrast to admissions in more centrally located urban hospital units. People from rural areas are all subsistence farmers, have poor income and low educational level and have no possibility for travelling within or outside the country. These factors are known to increase the prevalence of malnutrition and lower that of HIV [57, 61–64]. Lastly, the low HIV prevalence might also be explained by the high mortality of HIV infected infants biasing our data to include those children who have survive infancy. Without effective treatment, it is estimated that over 50% of infants who acquired HIV infection through mother-to-child transmission will die by two years of age (compared to 8% of uninfected children) while in Malawi kwashiorkor, the most common form of SAM in children, peaks between 18 to 23 months of age [65–68]. The relatively older average ages of children in both the PC (26.4 months) and RC cohorts (47.2 months), suggests the possibility of survival bias.
Our estimated adult HIV prevalence of 5.0% is predictably lower than the antenatal HIV prevalence rate in the central region (9.8%) but similar to comparable adult prevalence rates of 6.4% and 4.1% for the region and for an adjacent district, respectively, as reported in the 2004 Malawi Demographic and Health Survey [69, 70]. Our study suggests that targeting adult caretakers of malnourished children for HIV testing is feasible but additional outreach and counseling efforts may be needed to increase uptake.
Our analysis confirms that clinical algorithms designed to diagnose paediatric HIV are neither sufficiently sensitive nor specific in severely malnourished children and that blood tests are therefore required to confirm the diagnosis . In context where blood tests are not available, the combination of MUAC > 110 mm and absence of proxy indicators can be used to rule out the presence of HIV. These family history variables could be incorporated into future CTC protocols for confirmed or suspected paediatric HIV in setting without possibility of blood tests .
SAM is one of several criteria for initiating ART in HIV-positive children . The fact that some previously undiagnosed HIV-positive children recovered from malnutrition, and were still healthy and asymptomatic an average of 15 months after discharge from CTC without ART, suggests that the presence of malnutrition should not be the sole criteria for initiating ART in food insecure settings. One possibility is that initiation of ART could be reserved for children who do not respond to CTC or at least could be delayed until nutrition improvement to minimize antiretroviral side effects. Several studies have reported that HIV-infected children tend to develop marasmus rather than kwashiorkor and that CD4 count remains higher in HIV-infected children with kwashiorkor compared to those with marasmus [17, 74, 75]. Therefore, delayed initiation of ART could be considered for children with kwashiorkor. This approach could help to prevent unnecessary exposure to ARV drugs that have side effects and toxicity and to reduce the risk of developing resistance . Further research, probably in the form of randomized trials, is urgently needed to strengthen this evidence base before any change of practice is recommended.
Several limitations of our study deserve mention. This study was carried out in conjunction with an ongoing CTC programme and clinical records were reviewed in order to obtain data on nutritional recovery. Although programme procedures were standardized, we were unable to verify nutritional measurements for accuracy. As noted previously, the RC may be subject to survival bias, and therefore we have limited our use and interpretation of the RC data. The statistical power of these analyses is also limited by the small number of HIV-positive children in the study and by further reduction of the sample size due to missing data for age and nutritional status. Nevertheless, the data from both cohorts paint a consistent picture with regard to the potential positive impact of Community-based Therapeutic Care for managing SAM in HIV-positive and uninfected children in rural Africa.