Background

Data on paediatric reference laboratory values are limited for sub-Saharan Africa.

Objective

To describe the distribution of haematological and chemical pathology values among healthy infants from Malawi and Uganda.

Methods

A cross-sectional study was conducted among healthy infants, 0–6 months old, born to HIV-uninfected mothers recruited from two settings in Blantyre, Malawi and Kampala, Uganda. Chemical pathology and haematology parameters were determined using standard methods on blood samples. Descriptive analyses by age-group were performed based on 2004 Division of AIDS Toxicity Table age categories. Mean values and interquartile ranges were compared by site and age-group.

Results

A total of 541 infants were included altogether, 294 from Malawi and 247 from Uganda. Overall, the mean laboratory values were comparable between the two sites. Mean alkaline phosphatase levels were lower among infants aged ≤21 days while aspartate aminotransferase, creatinine, total bilirubin and gamma-glutamyl transferase were higher in those aged 0–7 days than in older infants. Mean haematocrit, haemoglobin and neutrophil counts were higher in the younger age-groups (<35 days) and overall were lower than US norms. Red and white blood cell counts tended to decrease after birth but increased after ~2 months of age. Mean basophil counts were higher in Malawi than in Uganda in infants aged 0–1 and 2–7 days; mean counts for eosinophils (for age groups 8–21 or older) and platelets (for all age groups) were higher in Ugandan than in Malawian infants. Absolute lymphocyte counts increased with infant age.

Conclusion

The chemical pathology and haematological values in healthy infants born to HIV-uninfected mothers were comparable in Malawi and Uganda and can serve as useful reference values in these settings.

Background

Use of multivitamin supplements during the pre-HAART era has been found to reduce viral load, enhance immune response, and generally improve clinical outcomes among HIV-infected adults. However, immune reconstitution is incomplete and significant mortality and opportunistic infections occur in spite of HAART. There is insufficient research information on whether multivitamin supplementation may be beneficial as adjunct therapy for HIV-infected individuals taking HAART. We propose to evaluate the efficacy of a single recommended daily allowance (RDA) of micronutrients (including vitamins B-complex, C, and E) in slowing disease progression among HIV-infected adults receiving HAART in Uganda.

Methods/Design

We are using a randomized, double-blind, placebo-controlled trial study design. Eligible patients are HIV-positive adults aged at least 18 years, and are randomized to receive either a placebo; or multivitamins that include a single RDA of the following vitamins: 1.4 mg B1, 1.4 mg B2, 1.9 mg B6, 2.6 mcg B12, 18 mg niacin, 70 mg C, 10 mg E, and 0.4 mg folic acid. Participants are followed for up to 18 months with evaluations at baseline, 6, 12 and 18 months. The study is primarily powered to examine the effects on immune reconstitution, weight gain, and quality of life. In addition, we will examine the effects on other secondary outcomes including the risks of development of new or recurrent disease progression event, including all-cause mortality; ARV regimen change from first- to second-line therapy; and other adverse events as indicated by incident peripheral neuropathy, severe anemia, or diarrhea.

Discussions

The conduct of this trial provides an opportunity to evaluate the potential benefits of this affordable adjunct therapy (multivitamin supplementation) among HIV-infected adults receiving HAART in a developing country setting.

Trial registration

Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01228578

HIV-infected infants may have CXCR4-using (X4-tropic) HIV, CCR5-using (R5-tropic) HIV, or a mixture of R5-tropic and X4-tropic HIV (dual/mixed, DM HIV). The level of infectivity for R5 virus (R5-RLU) varies among HIV-infected infants. HIV tropism and R5-RLU were measured in samples from HIV-infected Ugandan infants using a commercial assay. DM HIV was detected in 7/72 (9.7%) infants at the time of HIV diagnosis (birth or 6–8 weeks of age, 4/15 (26.7%) with subtype D, 3/57 (5.3 %) with other subtypes, P=0.013). A transition from R5-tropic to DM HIV was observed in only two (6.7%) of 30 infants over 6–12 months. Six (85.7%) of seven infants with DM HIV died, compared to 21/67 (31.3%) infants with R5-tropic HIV (p=0.09). Higher R5-RLU at 6–8 weeks was not associated with decreased survival. Infants with in utero infection had a higher median R5-RLU than infants who were HIV-uninfected at birth (p=0.025).

Abstract

We analyzed drug resistance in HIV-infected Ugandan children who received antiretroviral therapy in a prospective, observational study (2004–2006); some children had prior single-dose nevirapine (sdNVP) exposure. Children received stavudine (d4T), lamivudine (3TC), and nevirapine (NVP); treatment was continued if they were clinically and immunologically stable. Samples with >1,000 copies/ml HIV RNA were analyzed by using the ViroSeq HIV Genotyping System (ViroSeq). Subtype A and D pretreatment samples also were analyzed with the LigAmp assay (for K103N, Y181C, and G190A). ViroSeq results were obtained for 74 pretreatment samples (35 from sdNVP-exposed children (median age, 19 months) and 39 from sdNVP-unexposed children (median age, 84 months). This included 39 subtype A, 22 subtype D, 1 subtype C, and 12 inter-subtype recombinant samples. One sample had nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance, one had nucleoside reverse transcriptase inhibitor (NRTI) resistance, and three had protease inhibitor (PI) resistance. Y181C was detected by using LigAmp in five pretreatment samples [four (14.8%) of 37 samples from sdNVP-exposed children, one (4.2%) of 24 samples from children without prior sdNVP exposure; p = 0.35]. Among children who were not virally suppressed at 48 weeks of treatment, all 12 tested had NNRTI resistance, as well as resistance to 3TC and emtricitibine (FTC); three had resistance to other NRTIs. Seven of those children had a ViroSeq result at 96 weeks of treatment; four of the seven acquired resistance to additional NRTIs by 96 weeks. In Uganda, clinically and immunologically stable children receiving nonsuppressive antiretroviral treatment regimens are at risk for development of drug resistance.

OBJECTIVE

Single-dose nevirapine (sdNVP) can reduce the risk of HIV vertical transmission. We assessed risk factors for NVP resistance in plasma and breast milk from sdNVP-exposed Ugandan women.

METHODS

Samples were analyzed using the Roche AMPLICOR HIV-1 Monitor Test Kit, v1.5, and the ViroSeq HIV-1 Genotyping System. NVP concentrations were determined by liquid chromatography with tandem mass spectroscopy.

RESULTS

HIV genotypes (plasma and breast milk) were obtained for 30 women 4 weeks after sdNVP (HIV subtypes: 15A, 1C, 12D, 2 recombinant). NVP resistance was detected in 12 (40%) of 30 breast milk samples. There was a non-significant trend between detection of NVP resistance in breast milk and plasma (p=0.06). There was no association of HIV resistance in breast milk with median maternal pre-NVP viral load or CD4 cell count, median breast milk viral load at 4 weeks, breast milk sodium >10 mmol/L, HIV subtype, or concentration of NVP in breast milk or plasma.

CONCLUSIONS

NVP resistance was frequently detected in breast milk 4 weeks after sdNVP exposure. In this study, we were unable to identify specific factors associated with breast milk NVP resistance.

Objective

To assess serious gastroenteritis risk and mortality associated with early cessation of breastfeeding in infants enrolled in two prevention-of-maternal-to-child-HIV-transmission trials in Uganda.

Methods

We used hazard rates to evaluate serious gastroenteritis events by month of age and mortality among HIV-exposed uninfected infants enrolled in the HIVNET 012 (1997-2001) and HIVIGLOB/NVP (2004-2007) trials. HIV-infected mothers were counseled using local infant feeding guidelines current at the time.

Results

Breastfeeding cessation occurred earlier in HIVIGLOB/NVP compared to HIVNET 012 (median 4.0 vs. 9.3 months, p<0.001). Rates of serious gastroenteritis were higher in HIVIGLOB/NVP (8.0/1000 child-months) compared to HIVNET 012 (3.1/1000 child-months; p < 0.001). Serious gastroenteritis events also peaked earlier at 3-4 and 7-8 months (16.2/1000 and 15.0/1000 child-months, respectively) compared to HIVNET 012 at 9 to10 months (20.8/1000 child-months). All cause-infant mortality did not statistically differ between the HIVIGLOB/NVP and the HIVNET 012 trials [3.2/1000 versus 2.0/1000 child-months respectively, (p=0.10)]

Conclusion

Early breastfeeding cessation seen in the HIVIGLOB/NVP trial was associated with increased risk of serious gastroenteritis among HIV-exposed uninfected infants when compared to later breastfeeding cessation in the HIVNET 012 trial. Testing interventions which could decrease HIV transmission through breastfeeding and allow safe breastfeeding into the second year of life are urgently needed.

Objectives

To determine normal hematologic and selected blood chemistry values among healthy, full-term, non–HIV-exposed infants in Uganda and Malawi, and to determine the proportion of healthy babies with an apparent laboratory toxicity based on Division of AIDS toxicity tables.

Design

This was a cross-sectional laboratory study of infants from birth to 6 months of age.

Methods

Blood samples were collected from a total of 561 infants and analyzed according to age categories similar to those in the 2004 Division of AIDS toxicity tables. Select chemistry and hematology parameters were determined and values compared with those in the toxicity tables.

Results

In the first 56 days of life, there were few graded toxicities except for neutropenia in 2 of 10 (20%) Ugandan and 13 of 45 (29%) Malawian infants at birth. After 7 days, about 20% of the infants in Uganda and Malawi would have been classified as having a neutropenia whereas 47% and 53% of those more than 2 months of age in Uganda and Malawi respectively, would have been reported as having an abnormal hemoglobin. Chemistry findings were not different from US norms.

Conclusions

These findings underscore the importance of establishing relevant local laboratory norms for infants.

Background

Scale up of paediatric antiretroviral therapy in resource limited settings continues despite limited access to routine laboratory monitoring. We documented the weight and height responses in HIV infected Ugandan children on highly active antiretroviral therapy and determined clinical factors associated with successful treatment outcomes.

Methods

A prospective cohort of HIV infected children were initiated on HAART and followed for 48 weeks. Body mass index for age z scores(BAZ), weight and height-for-age z scores (WAZ & HAZ) were calculated: CD4 cell % and HIV-1 RNA were measured at baseline and every 12 weeks. Treatment outcomes were classified according to; both virological and immunological success (VS/IS), virological failure and immunological success (VF/IS). virological success and immunological failure (VS/IF) and both virological and immunological failure (VF/IF).

Results

From March 2004 until May 2006, 124 HIV infected children were initiated on HAART. The median age (IQR) was 5.0 years (2.1 - 7.0) and 49% (61/124) were female. The median [95% confidence interval (CI)] BAZ, WAZ and HAZ at baseline were 0.29 (-2.9, -1.2), -1.2 (-2.1, -0.5) and -2.06 (-2.9, -1.2) respectively. Baseline median CD4 cell % and log10 HIV-1 RNA were; 11.8% (7.5-18.0) and 5.6 (5.2-5.8) copies/ml. By 48 weeks, mean WAZ and HAZ in the VF/IS group, which was younger, increased from - 0.98 (SD 1.7) to + 1.22 (SD 1.2) and from -1.99 (1.7) to + 0.76 (2.4) respectively. Mean increase in WAZ and HAZ in the VS/IF group, an older group was modest, from -1.84 (1.3) to - 0.41 (1.2) and -2.25 (1.2) to -1.16 (1.3) respectively. Baseline CD4 cell % [OR 6.97 95% CI (2.6 -18.6)], age [OR 4.6 95% CI (1.14 -19.1)] and WHO clinical stage [OR 3.5 95%CI (1.05 -12.7)] were associated with successful treatment outcome.

Conclusions

HIV infected Ugandan children demonstrated a robust increase in height and weight z scores during the first 48 weeks of HAART, including those who failed to completely suppress virus. Older children initiating HAART with severe immune suppression were less likely to achieve a successful treatment outcome. These data emphasize the importance of initiating HAART early to ensure adequate immune and growth responses.

Use of single dose nevirapine (sdNVP) to prevent HIV mother-to-child transmission is associated with the emergence of NVP resistance in many infants who are HIV infected despite prophylaxis. We combined results from four clinical trials to analyze predictors of NVP resistance in sdNVP-exposed Ugandan infants. Samples were tested with the ViroSeq HIV Genotyping System and a sensitive point mutation assay (LigAmp, for detection of K103N, Y181C, and G190A). NVP resistance was detected at 6–8 weeks in 36 (45.0%) of 80 infants using ViroSeq and 33 (45.8%) of 72 infants using LigAmp. NVP resistance was more frequent among infants who were infected in utero than among infants who were diagnosed with HIV infection after birth by 6–8 weeks of age. Detection of NVP resistance at 6–8 weeks was not associated with HIV subtype (A vs. D), pre-NVP maternal viral load or CD4 cell count, infant viral load at 6–8 weeks, or infant sex. NVP resistance was still detected in some infants 6–12 months after sdNVP exposure. In this study, in utero HIV infection was the only factor associated with detection of NVP resistance in infants 6–8 weeks after sdNVP exposure.

Abstract

Use of single dose nevirapine (sdNVP) to prevent HIV mother-to-child transmission is associated with the emergence of NVP resistance in many infants who are HIV infected despite prophylaxis. We combined results from four clinical trials to analyze predictors of NVP resistance in sdNVP-exposed Ugandan infants. Samples were tested with the ViroSeq HIV Genotyping System and a sensitive point mutation assay (LigAmp, for detection of K103N, Y181C, and G190A). NVP resistance was detected at 6–8 weeks in 36 (45.0%) of 80 infants using ViroSeq and 33 (45.8%) of 72 infants using LigAmp. NVP resistance was more frequent among infants who were infected in utero than among infants who were diagnosed with HIV infection after birth by 6–8 weeks of age. Detection of NVP resistance at 6–8 weeks was not associated with HIV subtype (A vs. D), pre-NVP maternal viral load or CD4 cell count, infant viral load at 6–8 weeks, or infant sex. NVP resistance was still detected in some infants 6–12 months after sdNVP exposure. In this study, in utero HIV infection was the only factor associated with detection of NVP resistance in infants 6–8 weeks after sdNVP exposure.

Single dose (SD) nevirapine (NVP) significantly reduces HIV mother-to-child transmission. We analyzed NVP resistance after SD NVP in 57 previously SD NVP-naїve women, 34 SD NVP-experienced women, and 17 HIV-infected infants. The proportion of women with resistance, the types of mutations detected, and the frequency and level of K103N were similar in the two groups of women at 6 weeks and 6 months post-partum. NVP resistance was detected in a similar proportion of infants born to SD NVP-naїve versus SD NVP-experienced women. Repeated use of SD NVP to prevent HIV transmission does not appear to influence NVP resistance.