Transferrin polymorphism and opportunistic infections in HIV-infected women in Rwanda.

OBJECTIVE: We investigated the prevalence of opportunistic infections in HIV-infected women according to transferrin (TF) phenotype. METHODS: We conducted a cross-sectional study among 200 HIV-positive women in the Butare University Teaching Hospital in Rwanda. TF phenotypes were determined using starch gel electrophoresis. RESULTS: Phenotype frequencies of TF CD, CB and CC were 14.5, 3 and 82.5%, respectively. The homozygous TF DD phenotype was not found. Subjects with TF CD phenotype had a significantly higher prevalence of opportunistic infections than subjects with TF CC phenotype, 76 and 52%, respectively (p = 0.026). In logistic regression, there was a significant correlation between TF phenotypes and opportunistic infections (p = 0.012). Subjects with TF CD phenotype had significantly lower values for TF (p = 0.006) than TF CC subjects. Hematological parameters (RBC, RBC indices, hemoglobin, hematocrit, WBC, neutrophils, lymphocytes, platelets and erythrocyte sedimentation rate), iron, ferritin, TF saturation, C-reactive protein and CD4 count did not differ according to TF phenotype. CONCLUSION: Subjects with TF CC phenotype have a lower prevalence of opportunistic infections. Iron status may play a role in this association.

Ferroportin (SLC40A1) Q248H mutation is associated with lower circulating serum hepcidin levels in Rwandese HIV-positive women.

The Q248H mutation in the gene SLC40A1 which encodes for the cellular iron exporter ferroportin is relatively common in Africa. This mutation has been associated with resistance to hepcidin and therefore we hypothesized that iron-related parameters and the prevalence of opportunistic infections in HIV might be influenced by the Q248H mutation. We conducted a cross-sectional study among 200 HIV-positive women in the Butare University Teaching Hospital in Rwanda. Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the Q248H mutation. Physical examination was carried out and WHO HIV disease stage classification, complete blood count, CD4 count, indirect measures of iron status, serum hepcidin, and C-reactive protein concentrations were determined. The prevalence of ferroportin Q248H mutation was 6%. Subjects with ferroportin Q248H mutation had significantly higher values for serum ferritin (P = 0.001) and significantly lower values for serum hepcidin (P = 0.001) and transferrin (P = 0.01). Among the 12 HIV + Q248H heterozygotes, 8 suffered from at least one opportunistic infection. There was significantly higher prevalence of pulmonary TB (P = 0.01) and Pneumocystis jiroveci pneumonia (P = 0.02) in subjects with ferroportin Q248H mutation. Low hepcidin levels were found in ferroportin Q248H heterozygotes with HIV infection, notwithstanding the absence of anemia and the higher prevalence of some opportunistic infections. Hepcidin seems to be regulated in a different way in Q248H heterozygotes than is known thus far.

Anemia in human immunodeficiency virus-infected and uninfected women in Rwanda.

To determine the prevalence and risk factors of anemia among human immunodeficiency virus (HIV)-infected women in Rwanda and the influence of highly active antiretroviral therapy (HAART) on anemia, we analyzed 200 HIV-positive women and 50 HIV-negative women in a cross-sectional study. Clinical examinations and iron and vitamin B(12) assays were performed, and complete blood counts, serum folic acid levels, and CD4 cell count determined. The prevalence of anemia was significantly higher among HIV-positive women (29%) than among HIV-negative women (8%) (P < 0.001). Risk factors for anemia were lower body mass index (odds ratio [OR] = 3.4, 95% confidence interval [CI] = 2.4-4.1), zidovudine use (OR = 1.14, 95% CI = 1.01-1.29), lack of HAART (OR = 1.44, 95% CI = 1.21-1.67), oral candidiasis (OR = 1.4, 95% CI = 1.2-1.6), pulmonary tuberculosis (OR = 1.8, 95% CI = 1.7-2.2), cryptococcal meningitis (OR = 1.6, 95% CI = 1.21-1.8), Pneumocystis jiroveci pneumonia (OR = 1.41, 95% CI = 1.20-1.65) and CD4 lymphocyte count < 200 cells/µL (OR = 2.41, 95% CI = 2.01-3.07). The mean ± SD hemoglobin level of 10.9 ± 1.6 g/dL at HAART initiation significantly increased to 12.3 ± 1.5 g/dL in 8 months (P < 0.001). Anemia increases with HIV stage, and HAART is associated with a significant improvement in hemoglobin levels.

Interpreting tests for iron deficiency among adults in a high HIV prevalence African setting: routine tests may lead to misdiagnosis.

We evaluated peripheral blood tests to diagnose iron deficiency on medical wards in Blantyre, Malawi, where infection and HIV are prevalent. We compared full blood count, ferritin and serum transferrin receptor (TfR) levels with an estimation of iron in bone marrow aspirates. Of consecutive adults admitted with severe anaemia (haemoglobin <7 g/dl), 81 had satisfactory bone marrow aspirates. The main outcome measures were the validity of each test (sensitivity, specificity, and positive and negative predictive values) and likelihood ratios (LR) for iron deficiency. Twenty patients (25%) were iron deficient and 64 (79%) were HIV-positive. Iron deficiency was more common in HIV-negative compared with HIV-positive patients (59% vs. 16%; P<0.001). In HIV-positive patients, the optimal ferritin cut-off was 150 microg/l (sensitivity 20%, specificity 93%, LR 2.7), but no test was accurate enough to be clinically useful. In HIV-negative patients, ferritin was the single most accurate test (cut-off <70 microg/l, 100% specificity, 90% sensitive, LR if positive infinity, LR if negative 10). TfR measurement did not improve the accuracy. Mean cell volume was not a good predictor of iron status except in HIV-negative patients (cut-off <85 fl, specificity 71%, sensitivity 90%). In populations with high levels of infection and HIV, an HIV test is necessary to interpret any tests of iron deficiency. In HIV-negative patients, ferritin is the best blood test for iron deficiency, using a higher cut-off than usual. For HIV-positive patients, it is difficult to diagnose iron deficiency without bone marrow aspirates.

Treatable factors associated with severe anaemia in adults admitted to medical wards in Blantyre, Malawi, an area of high HIV seroprevalence.

Severe anaemia is a common presentation in non-pregnant adults admitted to hospital in southern Africa. Standard syndromic treatment based on data from the pre-HIV era is for iron deficiency, worms and malaria. We prospectively investigated 105 adults admitted consecutively to medical wards with haemoglobin < 7 g/dl. Those with acute blood loss were excluded. Patients were investigated for possible parasitic, bacterial, mycobacterial and nutritional causes of anaemia, including bone marrow aspiration, to identify potentially treatable causes. Seventy-nine per cent of patients were HIV-positive. One-third of patients had tuberculosis, which was diagnosed only by bone marrow culture in 8% of HIV-positive patients. In 21% of individuals bacteria were cultured, with non-typhi salmonella predominating and Streptococcus pneumoniae rare. Iron deficiency, hookworm infection and malaria were not common in HIV-positive anaemic adults, although heavy hookworm infections were found in 6 (27%) of the 22 HIV-negative anaemic adults. In conclusion, conventional treatment for severe anaemia in adults is not appropriate in an area of high HIV prevalence. Occult mycobacterial disease and bacteraemia are common, but iron deficiency is not common in HIV-positive patients. In addition to iron supplements, management of severe anaemia should include investigation for tuberculosis, and consideration of antibiotics active against enterobacteria.

Haematological changes in African children who received short-term prophylaxis with nevirapine and zidovudine at birth.

We assessed the safety of short-term antiretroviral prophylaxis to prevent mother-to-child transmission (MTCT) of HIV by monitoring haematological changes in children up to the age of 18 months. Babies of HIV-infected women were randomised at birth to receive a single dose of nevirapine (NVP) alone or with zidovudine (ZDV) twice daily for a week. Based on the time of presentation to the labour ward, mothers of these babies might or might not have received intrapartum NVP. Complete blood counts were performed at birth and at 1.5, 3, 6, 9, 12, 15 and 18 months. Babies' HIV status was determined by HIV-1 RNA testing. A total of 1755 babies were included in the study. Age-specific mean haemoglobin levels and prevalence of anaemia (haemoglobin < 10 g/dL) were not significantly different in cases where only the babies received a single dose of NVP and cases where NVP was given to mother/infant pairs or additional ZDV to the baby. Among HIV-infected children compared with uninfected children, the age-specific frequency of anaemia was significantly greater, anaemia started earlier and recovery to normal levels was slower and prolonged. A reversible granulocytopenia was observed in all children between 1.5 and 3 months of age. HIV infection significantly increased the children's risk of death. Antiretroviral prophylaxis appeared to protect against anaemia and child death. Short regimens of antiretrovirals to prevent MTCT of HIV are not associated with long-term adverse haematological changes.

Effect of HIV-1 antiretroviral prophylaxis on hepatic and hematological parameters of African infants.

OBJECTIVE: To measure hepatic and hematological parameters among neonates randomized to receive ultra-short antiretroviral regimens. DESIGN: As part of an on-going clinical trial in Malawi, infants born to women who received (early presenters) or did not receive (late presenters) standard intrapartum nevirapine (NVP) dosing were randomized to receive orally either single dose NVP alone or NVP plus zidovudine (twice daily for 1 week). An additional group of untreated infants (born to HIV-uninfected women) was enrolled as a control. METHODS: Laboratory measurements were performed at birth and repeated at 6 weeks of age. Serum alanine aminotransferase (ALT) was measured on approximately 200 infants consecutively enrolled and randomized at the start of the trial. Complete blood count (CBC) was performed on approximately 800 infants at birth and 600 infants at 6 weeks of age. ALT and CBC were also determined on approximately 200 control infants. RESULTS: At birth there were no differences in ALT values between the groups of children. At 6 weeks of age, ALT levels were significantly higher among the treated groups compared with control group (geometric mean of 11.5 U/l for controls and 16.2-19.1 U/l for treated groups; P < 0.0001). Hematological parameters did not differ between groups at birth. At 6 weeks of age, levels of hemoglobin, hematocrit, granulocytes, and platelets were significantly (P < 0.0001) lower among antiviral drug-treated groups compared with controls. These changes were consistent with grade 1 (mild) toxicity, and were more noticeable among HIV-infected infants. CONCLUSIONS: Hepatic and hematologic abnormalities associated with short-term neonatal antiretrovirals among African children are minimal.