Changes in measles serostatus among HIV-infected Zambian children initiating antiretroviral therapy before and after the 2010 measles outbreak and supplemental immunization activities.

BACKGROUND: In 2010, Zambia had a large measles outbreak, providing an opportunity to measure changes in measles serostatus following highly active antiretroviral therapy (HAART), exposure to measles virus, and revaccination among children infected with human immunodeficiency virus (HIV). METHODS: A prospective cohort study of 169 HIV-infected Zambian children aged 9-60 months with a history of measles vaccination was conducted to characterize the effects of HAART and revaccination on measles immunoglobulin G (IgG) serostatus by enzyme immunoassay. RESULTS: Prior to the measles outbreak, only 23% of HIV-infected children were measles IgG seropositive at HAART initiation. After adjusting for 6-month changes in baseline age and 5% changes in nadir CD4(+) T-cell percentage, HAART was not associated with measles IgG seroconversion. However, 18 of 19 children seroconverted after revaccination. Eight children seroconverted during the outbreak without revaccination and were likely exposed to wild-type measles virus, but none were reported to have had clinical measles. CONCLUSIONS: Immune reconstitution after HAART initiation did not restore protective levels of measles IgG antibodies, but almost all children developed protective antibody levels after revaccination. Some previously vaccinated HIV-infected children had serological evidence of exposure to wild-type measles virus without a reported history of measles.

Task-Shifting and Quality of HIV Testing Services: Experiences from a National Reference Hospital in Zambia.

BACKGROUND: With new testing technologies, task-shifting and rapid scale-up of HIV testing services in high HIV prevalence countries, assuring quality of HIV testing is paramount. This study aimed to explore various cadres of providers' experiences in providing HIV testing services and their understanding of elements that impact on quality of service in Zambia. METHODS: Sixteen in-depth interviews and two focus group discussions were conducted with HIV testing service providers including lay counselors, nurses and laboratory personnel at purposively selected HIV testing sites at a national reference hospital in Lusaka. Qualitative content analysis was adopted for data analysis. RESULTS: Lay counselors and nurses reported confidentiality and privacy to be greatly compromised due to limited space in both in- and out-patient settings. Difficulties in upholding consent were reported in provider-initiated testing in in-patient settings. The providers identified non-adherence to testing procedures, high workload and inadequate training and supervision as key elements impacting on quality of testing. Difficulties related to testing varied by sub-groups of providers: lay counselors, in finger pricking and obtaining adequate volumes of specimen; non-laboratory providers in general, in interpreting invalid, false-negative and false-positive results. The providers had been participating in a recently established national HIV quality assurance program, i.e. proficiency testing, but rarely received site supervisory visits. CONCLUSION: Task-shifting coupled with policy shifts in service provision has seriously challenged HIV testing quality, protection of confidentiality and the process of informed consent. Ways to better protect confidentiality and informed consent need careful attention. Training, supervision and quality assurance need strengthening tailored to the needs of the different cadres of providers.

Antiretroviral therapy restores age-dependent loss of resting memory B cells in young HIV-infected Zambian children.

BACKGROUND: Antiretroviral therapy (ART) is associated with incomplete restoration of resting memory B (RMB) cell percentages in adults infected with HIV, but the effects on RMB cells in children are less well defined, in part because changes in RMB cell percentages are confounded by the development and maturation of the RMB cell pool. The objective of this study was to assess the effect of age at ART initiation on RMB cell percentages over time in HIV-infected Zambian children. METHODS: RMB cell percentages (CD19CD21CD27) were measured by flow cytometry in 146 HIV-infected Zambian children (9-120 months old) at baseline and at 3-month intervals after ART initiation and in 34 control children at a single study visit. RESULTS: RMB cell percentages among untreated HIV-infected children younger than 24 months did not differ from those of control children (P = 0.97). Among HIV-infected children older than 24 months of age, however, each 12-month increase in age at ART initiation was associated with a 1.8% decrease in RMB cell percentage. In contrast, RMB cell percentages in control children up to 48 months increased 4.4% with each 12-month increase in age. After 12 months of ART, children aged 24-60 months had a significant increase in RMB cell percentages that no longer differed from those of control children. CONCLUSIONS: Initiation of ART in 2- to 5-year-old HIV-infected children resulted in reconstitution of RMB cell percentages to levels similar to control children and may help restore normal development and maintenance of B-cell immunity.

Immunologic risk factors for early mortality after starting antiretroviral therapy in HIV-infected Zambian children.

To explore immunologic risk factors for death within 90 days of highly active antiretroviral therapy (HAART) initiation, CD4(+) and CD8(+) T cell subsets were measured by flow cytometry and characterized by logistic regression in 149 Zambian children between 9 months and 10 years of age enrolled in a prospective, observational study of the impact of HAART on measles immunity. Of 21 children who died during follow-up, 17 (81%) had known dates of death and 16 (76%) died within 90 days of initiating HAART. Young age and low weight-for-age z-scores were associated with increased risks of mortality within 90 days of starting HAART, whereas CD4(+) T cell percentage was not associated with mortality. After adjusting for these factors, each 10% increase in CD8(+) effector T cells increased the odds of overall mortality [OR=1.43 (95% CI: 1.08, 1.90)] and was marginally associated with early mortality [OR=1.29 (95% CI: 0.97, 1.72)]. Conversely, each 10% increase in CD4(+) central memory T cells decreased the odds of overall [OR=0.06 (95% CI: 0.01, 0.59)] and early mortality [OR=0.09 (95% CI: 0.01, 0.97)]. Logistic regression prediction models demonstrated areas under the receiver-operator characteristic curves of ≥85% for early and overall mortality, with bootstrapped sensitivities of 82-85% upon validation, supporting the predictive accuracy of the models. CD4(+) and CD8(+) T cell subsets may be more accurate predictors of early mortality than CD4(+) T cell percentages and could be used to identify children who would benefit from more frequent clinical monitoring after initiating HAART.