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1.  Performance of modified WHO presumptive criteria for diagnosis of HIV infection in children <18 months admitted to University Teaching Hospital in Lusaka 
Medical journal of Zambia  2010;37(2):64-70.
Making a diagnosis of HIV infection in children aged less than 18 months remains a challenge in low resource settings like Zambia due to the limited availability of gold standard testing with HIV DNA PCR. Clinicians in rural areas have to depend on clinical diagnosis to start HAART as they wait for the dry blood spot (DBS) for DNA PCR results sent from the urban centers.
This descriptive cross-sectional study was performed at the University Teaching Hospital, Lusaka, Zambia. 299 HIV-exposed children aged less than 18 months were enrolled following a consent procedure. Patients were evaluated for HIV infection based on the World Health Organization’s presumptive diagnostic criteria (WHO-PDC), integrated management of childhood illnesses (IMCI) criteria, select physical exam abnormalities, and CD4% and findings were compared with HIV-DNA PCR results.
Of the 299 exposed patients analyzed, 111(37%) were found to be HIV-positive by DNA PCR. The median CD4% in the infected children was 18%. WHO-PDC used on its own had 23% sensitivity (95% CI 17–32%) and 93% specificity (88–96%), respectively, whereas IMCI criterion had 10% sensitivity (6–17%) and 97% specificity (94–99%), respectively. Multivariate analysis was used to identify the most sensitive predictors when combined with the WHO-PDC and IMCI criterion. WHO-PDC with CD4% improved the sensitivity to 77% (68–83%) with a specificity of 83% (77–88%), positive predictive value (PPV) of 73% (64–80%) and negative predictive value (NPV) of 86% (80–90%). IMCI with CD4% improved sensitivity to 80% (71–87%) with a specificity of 88% (82–92%), PPV 78% (69–85%) and NPV 89% (84–93%). The addition of individual physical exam findings without CD4% improved the sensitivity of WHO-PDC only modestly. When the WHO-PDC, weight<3rd percentile, hepatomegaly, splenomegaly, lymphadenopathy and CD4% were combined, the sensitivity improved to 85% (77–90%), specificity 63% (56–70%), PPV 58% (50–65%) and NPV of 88% (81–92%).
The WHO-PDC clinical algorithm can be improved when combined with a CD4% <25% in children less than 12 months of age and CD4% <20% in those between 12 and 18 months.
PMCID: PMC3500600  PMID: 23170039
HIV; early infant diagnosis; diagnosis; Zambia
2.  Treatment of Young Children with HIV Infection: Using Evidence to Inform Policymakers 
PLoS Medicine  2012;9(7):e1001273.
Andrew Prendergast and colleagues consider the evidence for a change in policy for the treatment of young children infected with HIV.
PMCID: PMC3404108  PMID: 22910874
3.  Diarrhea is a Major killer of Children with Severe Acute Malnutrition Admitted to Inpatient Set-up in Lusaka, Zambia 
Nutrition Journal  2011;10:110.
Mortality of children with Severe Acute Malnutrition (SAM) in inpatient set-ups in sub-Saharan Africa still remains unacceptably high. We investigated the prevalence and effect of diarrhea and HIV infection on inpatient treatment outcome of children with complicated SAM receiving treatment in inpatient units.
A cohort of 430 children aged 6-59 months old with complicated SAM admitted to Zambia University Teaching Hospital's stabilization centre from August to December 2009 were followed. Data on nutritional status, socio-demographic factors, and admission medical conditions were collected up on enrollment. T-test and chi-square tests were used to compare difference in mean or percentage values. Logistic regression was used to assess risk of mortality by admission characteristics.
Majority, 55.3% (238/430) were boys. The median age of the cohort was 17 months (inter-quartile range, IQR 12-22). Among the children, 68.9% (295/428) had edema at admission. The majority of the children, 67.3% (261/388), presented with diarrhea; 38.9% (162/420) tested HIV positive; and 40.5% (174/430) of the children died. The median Length of stay of the cohort was 9 days (IQR, 5-14 days); 30.6% (53/173) of the death occurred within 48 hours of admission. Children with diarrhea on admission had two and half times higher odds of mortality than those without diarrhea; Adjusted OR = 2.5 (95% CI 1.50-4.09, P < 0.001). The odds of mortality for children with HIV infection was higher than children without HIV infection; Adjusted OR = 1.6 (95% CI 0.99-2.48 P = 0.5).
Diarrhea is a major cause of complication in children with severe acute malnutrition. Under the current standard management approach, diarrhea in children with SAM was found to increase their odds of death substantially irrespective of other factors.
PMCID: PMC3214843  PMID: 21989455
diarrhea; HIV/AIDS; Severe Acute Malnutrition; Zambia; inpatient
4.  The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains 
Retrovirology  2011;8:31.
The Q151M multi-drug resistance (MDR) pathway in HIV-1 reverse transcriptase (RT) confers reduced susceptibility to all nucleoside reverse transcriptase inhibitors (NRTIs) excluding tenofovir (TDF). This pathway emerges after long term failure of therapy, and is increasingly observed in the resource poor world, where antiretroviral therapy is rarely accompanied by intensive virological monitoring. In this study we examined the genotypic, phenotypic and fitness correlates associated with the development of Q151M MDR in the absence of viral load monitoring.
Single-genome sequencing (SGS) of full-length RT was carried out on sequential samples from an HIV-infected individual enrolled in ART rollout. The emergence of Q151M MDR occurred in the order A62V, V75I, and finally Q151M on the same genome at 4, 17 and 37 months after initiation of therapy, respectively. This was accompanied by a parallel cumulative acquisition of mutations at 20 other codon positions; seven of which were located in the connection subdomain. We established that fourteen of these mutations are also observed in Q151M-containing sequences submitted to the Stanford University HIV database. Phenotypic drug susceptibility testing demonstrated that the Q151M-containing RT had reduced susceptibility to all NRTIs except for TDF. RT domain-swapping of patient and wild-type RTs showed that patient-derived connection subdomains were not associated with reduced NRTI susceptibility. However, the virus expressing patient-derived Q151M RT at 37 months demonstrated ~44% replicative capacity of that at 4 months. This was further reduced to ~22% when the Q151M-containing DNA pol domain was expressed with wild-type C-terminal domain, but was then fully compensated by coexpression of the coevolved connection subdomain.
We demonstrate a complex interplay between drug susceptibility and replicative fitness in the acquisition Q151M MDR with serious implications for second-line regimen options. The acquisition of the Q151M pathway occurred sequentially over a long period of failing NRTI therapy, and was associated with mutations in multiple RT domains.
PMCID: PMC3113953  PMID: 21569325
5.  Excellent Adherence to Antiretrovirals in HIV+ Zambian Children Is Compromised by Disrupted Routine, HIV Nondisclosure, and Paradoxical Income Effects 
PLoS ONE  2011;6(4):e18505.
A better understanding of pediatric antiretroviral therapy (ART) adherence in sub-Saharan Africa is necessary to develop interventions to sustain high levels of adherence.
Methodology/Principal Findings
Adherence among 96 HIV-infected Zambian children (median age 6, interquartile range [IQR] 2,9) initiating fixed-dose combination ART was measured prospectively (median 23 months; IQR 20,26) with caregiver report, clinic and unannounced home-based pill counts, and medication event monitoring systems (MEMS). HIV-1 RNA was determined at 48 weeks. Child and caregiver characteristics, socio-demographic status, and treatment-related factors were assessed as predictors of adherence. Median adherence was 97.4% (IQR 96.1,98.4%) by visual analog scale, 94.8% (IQR 86,100%) by caregiver-reported last missed dose, 96.9% (IQR 94.5,98.2%) by clinic pill count, 93.4% (IQR 90.2,96.7%) by unannounced home-based pill count, and 94.8% (IQR 87.8,97.7%) by MEMS. At 48 weeks, 72.6% of children had HIV-1 RNA <50 copies/ml. Agreement among adherence measures was poor; only MEMS was significantly associated with viral suppression (p = 0.013). Predictors of poor adherence included changing residence, school attendance, lack of HIV disclosure to children aged nine to 15 years, and increasing household income.
Adherence among children taking fixed-dose combination ART in sub-Saharan Africa is high and sustained over two years. However, certain groups are at risk for treatment failure, including children with disrupted routines, no knowledge of their HIV diagnosis among older children, and relatively high household income, possibly reflecting greater social support in the setting of greater poverty.
PMCID: PMC3080873  PMID: 21533031

Results 1-5 (5)