Virologic, immunologic and clinical response of infants to antiretroviral therapy in Kampala, Uganda.

BACKGROUND: Antiretroviral therapy (ART) is known to save lives. Among HIV-infected infants living in resource constrained settings, the short and long term benefits of ART are only partially known. This study was designed to determine the virologic, immunologic and clinical outcomes of antiretroviral therapy in a cohort of HIV-infected infants receiving care from an outpatient clinic in Kampala, Uganda. METHODS: A prospective cohort of HIV-infected infants receiving treatment at the Baylor-Uganda clinic was analyzed. Patients were diagnosed, enrolled and followed up at the clinic. HIV viral load, CD4 cell counts and clinical progress were assessed during follow-up. Descriptive statistical analysis and logistic regression modeling to determine predictors of treatment success were conducted. RESULTS: Of 91 HIV-infected infants enrolled into the cohort, 53 (58.2%) infants were female; 43 (47.3%) were 6 months of age or younger, and 50 (55.6%) had advanced HIV/AIDS disease (Clinical stage 3 or 4). Eighty four infants started ART and 78 (92.9%) completed 6 months of treatments. Fifty six (71.8%) infants attained virologic suppression by month-6 of ART, and at month-12 of ART, the cumulative probability of attaining viral suppression was 83.1%. None of the baseline infant factors (age, sex, WHO stage, CD4 cell percent, weight for age, or height for age z-score) predicted treatment success. There was an increase in CD4 cells from a baseline mean of 23% to 30% at month-6 of treatment (p<0.001) and by month-24 of ART, the mean CD4 percent was 36%. A total of 7 patients died while on ART and another 7 experienced adverse events that were related to treatment. CONCLUSION: Our results show that, even among very young patients from resource constrained settings, ART dramatically suppresses HIV replication, allows immune recovery and clinical improvement, and is safe. However, baseline characteristics do not predict recovery in this age group.

Lactose intolerance among severely malnourished children with diarrhoea admitted to the nutrition unit, Mulago hospital, Uganda.

BACKGROUND: Lactose intolerance is a common complication of diarrhoea in infants with malnutrition and a cause of treatment failure. A combination of nutritional injury and infectious insults in severe protein energy malnutrition reduces the capacity of the intestinal mucosa to produce lactase enzyme necessary for the digestion of lactose. The standard management of severe malnutrition involves nutritional rehabilitation with lactose-based high energy formula milk. However, some of these children may be lactose intolerant, possibly contributing to the high rate of unfavorable treatment outcomes. This study was therefore designed to establish the prevalence of lactose intolerance and associated factors in this population. METHODS: A descriptive cross sectional study involving 196 severely malnourished children with diarrhoea aged 3-60 months was done in Mwanamugimu Nutrition Unit (MNU), Mulago hospital between October 2006 and February 2007. RESULTS: During the study period, 196 severely malnourished children with diarrhoea were recruited, 50 (25.5%) of whom had evidence of lactose intolerance (stool reducing substance >or= 1 + [0.5%] and stool pH < 5.5) and it occurred more commonly in children with kwashiorkor 27/75 (36.0%) than marasmic-kwashiorkor 6/25 (24.0%) and marasmus 17/96 (17.7%). Oedematous malnutrition (p = 0.032), perianal skin erosion (p = 0.044), high mean stool frequency (p = < 0.001) and having >or=2 diarrhoea episodes in the previous 3 months (p = 0.007) were the independent predictors of lactose intolerance. Other factors that were significantly associated with lactose intolerance on bi-variate analysis included: young age of 3-12 months; lack of up to-date immunization; persistent diarrhoea; vomiting; dehydration, and abdominal distension. Exclusive breastfeeding for less than 4 months and worsening of diarrhoea on initiation of therapeutic milk were the other factors. CONCLUSIONS: The prevalence of lactose intolerance in this study setting of 25.5% is relatively high. Routine screening by stool pH and reducing substances should be performed especially in the severely malnourished children with diarrhoea presenting with oedematous malnutrition, perianal skin erosion, higher mean stool frequency and having had >or=2 diarrhoea episodes in the previous 3 months. Use of lactose-free diets such as yoghurt should be considered for children found to have evidence of lactose intolerance and whose response on standard therapeutic milk formula is poor.

Enteric bacterial pathogens in HIV-infected children with acute diarrhea in Mulago referral and teaching hospital, Kampala, Uganda.

OBJECTIVE: HIV-infected children develop severe bacterial infections. We set out to determine the enteric bacterial pathogens in HIV-infected children and HIV-negative controls with acute diarrhea and their antimicrobial sensitivities. METHODS: Children below 5 years of age with acute diarrhea were screened for HIV and their stools were analyzed by culture and use of antisera and the sensitivities of the pathogens were determined using the Kirby Bauer disc diffusion method. RESULTS: Of the 190 children, 47 were HIV positive. The prevalence rates of the pathogens in HIV-infected and -uninfected children were 19% (9/47) and 27% (38/143), respectively; odds ratio = 0.64 (95% confidence interval 0.20-1.97), P value .396. The pathogens in HIV-infected and -uninfected children were Escherichia coli, Salmonella, and Shigella species. Most isolates were resistant to cotrimoxazole. CONCLUSIONS: Escherichia coli, Salmonella, and Shigella species significantly cause acute diarrhea in HIV-infected and -uninfected children and they are highly resistant to cotrimoxazole.

Safety and tolerability of antiretroviral therapy among HIV-infected children and adolescents in Uganda.

BACKGROUND: Antiretroviral therapy (ART) is known to cause a number of adverse effects. The objective of this study was to determine the frequency and outcome of ART-related adverse events among patients aged 6 weeks to 18 years. METHODS: We followed up a cohort of 378 HIV-infected children and adolescents who started ART at the Baylor-Uganda Clinic during the period July 2004 to July 2009. Patients were started on zidovudine or stavudine, plus lamivudine, and efavirenz or nevirapine. Adverse events were recorded as they occurred. Descriptive analyses and Kaplan-Meier survival analysis were carried out. RESULTS: Of 126 adverse events reported among 107 (28.3%) patients, dizziness (17.5%), diarrhea (13.5%), and nausea and vomiting (14.3%) were the most frequent. Anxiety/night mares, skin rashes, nail discoloration, and lipodystrophy each contributed between 5% and 10%; whereas anorexia, abdominal pain, hepatitis, and somnolence contributed 1%-5%. Amnesia, lactic acidosis, gynaecomastia, cardiomyopathy, and peripheral neuropathy were rare, each contributing less than 1% of the total events. The overall probability of remaining free of adverse events was 77.1% (95% confidence interval: 72.38 to 81.13) at month 6 of ART.Among infants and young children, neurologic events could not be determined. Laboratory abnormalities were present at baseline and during follow-up, and hemoglobin levels increased significantly during the first 6 months of ART. There was no association between adverse events and baseline patient characteristics. CONCLUSION: Close to one-third of children on ART experience adverse events. Most events occur within the first 3 months of ART and are not associated with baseline patient characteristics.

Adherence to antiretroviral therapy in children attending Mulago Hospital, Kampala.

BACKGROUND: Non-adherence reduces the effectiveness of antiretroviral therapy in children attending the paediatric HIV/AIDS clinic at Mulago Hospital, Kampala. AIM: To determine the levels of adherence to HAART and identify factors associated with non-adherence. METHODS: A cross-sectional study of 170 children aged 2-18 years. Adherence to HAART was defined as taking > or =95% of prescribed medication. It was determined using three measures: a 3-day self-report by the caregivers, clinic-based pill counts at enrolment and home-based unannounced pill counts 2-3 weeks later. RESULTS: The 3-day self-reported > or =95% adherence was 89.4% (n=170). Using clinic-based pill counts, 94.1% (n=170) had > or =95% adherence to treatment compared with only 72% (n=164) by unannounced pill counts. When the primary caregiver was the only one who knew the child's serostatus, he/she was three times more likely to be non-adherent (p=0.02, OR 3.34, 95% CI 1.14-9.82). Those who had been hospitalised twice or more before starting HAART were more likely to have > or =95% adherence (p=0.02, OR 0.44, 95% CI 0.20-0.92). CONCLUSION: The majority of children had good adherence levels when estimated by unannounced pill counts. Disclosing the child's HIV serostatus only to the primary caregiver and having been hospitalised only once or not at all were associated with poor adherence.

Health, neurologic, and cognitive status of HIV-infected, long-surviving, and antiretroviral-naive Ugandan children.

OBJECTIVE: The purpose of this study was to assess the health status and school-age neurodevelopmental progress of antiretroviral treatment (ARVT)-naive, HIV-infected Ugandan children who had been followed as part of cohorts of children born to HIV-infected and -noninfected mothers between 1989 and 1993. METHODS: Twenty-eight children, aged 6 to 12 years, vertically infected with HIV-1 and never treated with ARVT were evaluated in terms of health status, neurologic, and psychometric testing. A randomly selected group of 42 seroreverters and 37 HIV-1 negative children who were age- and gender-matched and who had been followed in the same cohorts were evaluated also. The families studied were homogenous in their socioeconomic status. None of the mothers or children had received ARVT or been exposed to illicit drugs. RESULTS: The HIV-infected children showed significantly more evidence of acute malnutrition. They also had more illness, especially parotitis, otitis media, upper respiratory infections, and lymphadenopathy. However, they did not differ significantly in neurologic and cognitive assessments when compared with age- and gender-matched seroreverter and HIV-negative children. They were in the normal range with respect to neurologic and psychometric development measures. CONCLUSIONS: These children seem to represent a significant subgroup of HIV-infected child survivors for whom the progress of the disease is less aggressive throughout early life. Given the fact that many infants, especially in developing countries, continue to be born without the benefit of perinatal ARVT, there will likely continue to be many older HIV-infected children in the same situation as those described in this follow-up study. They will not have been recognized as being HIV-infected. It is important that such children be identified and offered access to ARVT and other appropriate support services.

Ocular manifestations in paediatric HIV/AIDS patients in Mulago Hospital, Uganda.

BACKGROUND: In Uganda the prevalence of HIV averages 12% as was reported to the STD/AIDS control surveillance unit. In Uganda there are approximately 30,000 HIV infected infants per year. The burden of HIV disease is high in Uganda and patients present with ocular complications. However, there is paucity of information and knowledge concerning ocular manifestations in the paediatric HIV/AIDS population and how they may differ from those of adults. OBJECTIVES: To describe the ocular manifestations of HIV/AIDS infection in an African paediatric population. Generally the study will record the external ocular manifestations seen but specifically to document the intra-ocular lesions, in particular the retinal changes associated with paediatric HIV/AIDS. DESIGN: A cross-sectional hospital based study. SETTING: The study was conducted at the Paediatric Infectious Disease Clinic at Upper Mulago Hospital, in Kampala, Uganda. PATIENTS: Patients are those with positive HIV sero status, with or without symptoms and signs of AIDS. Parents/caretakers of the children were interviewed to obtain the socio-demographic data of the patients and a general physical as well as an ophthalmic examination were conducted to document any ocular problems. RESULTS: A total of 158 HIV -infected children were examined. The overall rate of ophthalmic involvement was 35%. The most common finding was a non-purulent conjuctivitis, observed in 12% of the patients, followed by perivasculitis of the peripheral retinal vessels, in 12% of patients and molluscum contagiosum.

Effect of chloroquine on human immunodeficiency virus (HIV) vertical transmission.

INTRODUCTION: Over 2 million children globally are HIV positive. More than 90% are infected in utero from their mothers. Current pharmacological methods to reduce the rate of vertical transmission are too expensive for the developing world. Chloroquine, a cheap, widely available drug, has anti-HIV properties. We conducted a pilot study to determine if chloroquine can reduce HIV vertical transmission. METHODS: 287 samples of stored, frozen cord blood from a cohort of Ugandan infants born to HIV positive mothers were analyzed for concentrations of chloroquine and its two major metabolites, monodesethylchloroquine and didesethylchloroquine. The HIV status of each infant was determined by ELISA with Western Blot confirmation at 15 and 18 months of age. RESULTS: 49% of samples had measurable chloroquine or metabolite. Of those with measurable drug, the higher concentrations of chloroquine and its metabolites were more frequently associated with HIV negative infants. However, only the median concentration of didesethylochloroquine was significantly higher in HIV negative infants vs. HIV positive infants (1.6 ng/ml vs. 0.9 ng/ml, p=0.05). CONCLUSIONS: Nearly half of all infants in a Ugandan cohort are exposed to chloroquine in the last trimester of pregnancy. Such random maternal chloroquine use may be associated with a decreased rate of HIV vertical transmission. The issue of maternal chloroquine use requires controlled study before any clinical conclusions may be drawn.