Decrease in Seminal HIV-1 RNA Load After Praziquantel Treatment of Urogenital Schistosomiasis Coinfection in HIV-Positive Men-An Observational Study.

BACKGROUND: Urogenital schistosomiasis due to Schistosoma hematobium infection is hypothesized to cause increased HIV-1 RNA shedding in semen in HIV co-infected men as result of chronic egg-induced inflammation in the prostate and the seminal vesicles. The effect of treatment with the antihelminthic agent praziquantel on seminal HIV-1 RNA load was assessed in this study. METHODS: HIV-1 RNA load was determined in blood plasma and semen at baseline and at 10-week follow-up. Praziquantel was administered at baseline and two weeks later. RESULTS: Eighteen HIV-positive men with S. haematobium co-infection were enrolled into the study. Status of antiretroviral therapy (ART): 6 ART-naïve and 12 ART-experienced. All participants became egg-negative in urine at follow-up. Among the ART-naïve men, the mean HIV-1 RNA load decreased by 0.32 log10 copies per mL (4.41 vs 4.09) in blood plasma from baseline to follow-up, and in semen by 1.06 log10 copies per mL (4.06 vs 3.00). CONCLUSIONS: This study demonstrated a decline in seminal HIV-1 RNA load following praziquantel treatment of urogenital schistosomiasis infection in HIV-positive men. The finding needs further exploration in a larger randomized study targeting praziquantel as a supplementary preventive measure of sexual transmission of HIV-1 in S. haematobium endemic areas in sub-Saharan Africa.

Virological response and resistance among HIV-infected children receiving long-term antiretroviral therapy without virological monitoring in Uganda and Zimbabwe: Observational analyses within the randomised ARROW trial.

BACKGROUND: Although WHO recommends viral load (VL) monitoring for those on antiretroviral therapy (ART), availability in low-income countries remains limited. We investigated long-term VL and resistance in HIV-infected children managed without real-time VL monitoring. METHODS AND FINDINGS: In the ARROW factorial trial, 1,206 children initiating ART in Uganda and Zimbabwe between 15 March 2007 and 18 November 2008, aged a median 6 years old, with median CD4% of 12%, were randomised to monitoring with or without 12-weekly CD4 counts and to receive 2 nucleoside reverse transcriptase inhibitors (2NRTI, mainly abacavir+lamivudine) with a non-nucleoside reverse transcriptase inhibitor (NNRTI) or 3 NRTIs as long-term ART. All children had VL assayed retrospectively after a median of 4 years on ART; those with >1,000 copies/ml were genotyped. Three hundred and sixteen children had VL and genotypes assayed longitudinally (at least every 24 weeks). Overall, 67 (6%) switched to second-line ART and 54 (4%) died. In children randomised to WHO-recommended 2NRTI+NNRTI long-term ART, 308/378 (81%) monitored with CD4 counts versus 297/375 (79%) without had VL <1,000 copies/ml at 4 years (difference = +2.3% [95% CI -3.4% to +8.0%]; P = 0.43), with no evidence of differences in intermediate/high-level resistance to 11 drugs. Among children with longitudinal VLs, only 5% of child-time post-week 24 was spent with persistent low-level viraemia (80-5,000 copies/ml) and 10% with VL rebound ≥5,000 copies/ml. No child resuppressed <80 copies/ml after confirmed VL rebound ≥5,000 copies/ml. A median of 1.0 (IQR 0.0,1.5) additional NRTI mutation accumulated over 2 years' rebound. Nineteen out of 48 (40%) VLs 1,000-5,000 copies/ml were immediately followed by resuppression <1,000 copies/ml, but only 17/155 (11%) VLs ≥5,000 copies/ml resuppressed (P < 0.0001). Main study limitations are that analyses were exploratory and treatment initiation used 2006 criteria, without pre-ART genotypes. CONCLUSIONS: In this study, children receiving first-line ART in sub-Saharan Africa without real-time VL monitoring had good virological and resistance outcomes over 4 years, regardless of CD4 monitoring strategy. Many children with detectable low-level viraemia spontaneously resuppressed, highlighting the importance of confirming virological failure before switching to second-line therapy. Children experiencing rebound ≥5,000 copies/ml were much less likely to resuppress, but NRTI resistance increased only slowly. These results are relevant to the increasing numbers of HIV-infected children receiving first-line ART in sub-Saharan Africa with limited access to virological monitoring. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN24791884.

Finger Prick Dried Blood Spots for HIV Viral Load Measurement in Field Conditions in Zimbabwe.

BACKGROUND: In the context of a community-randomized trial of antiretrovirals for HIV prevention and treatment among sex workers in Zimbabwe (the SAPPH-IRe trial), we will measure the proportion of women with HIV viral load (VL) above 1000 copies/mL ("VL>1000") as our primary endpoint. We sought to characterize VL assay performance by comparing results from finger prick dried blood spots (DBS) collected in the field with plasma samples, to determine whether finger prick DBS is an acceptable sample for VL quantification in the setting. METHODS: We collected whole blood from a finger prick onto filter paper and plasma samples using venipuncture from women in two communities. VL quantification was run on samples in parallel using NucliSENS EasyQ HIV-1 v2.0. Our trial outcome is the proportion of women with VL>1000, consistent with WHO guidelines relating to regimen switching. We therefore focused on this cut-off level for assessing sensitivity and specificity. Results were log transformed and the mean difference and standard deviation calculated, and correlation between VL quantification across sample types was evaluated. RESULTS: A total of 149 HIV-positive women provided DBS and plasma samples; 56 (63%) reported being on antiretroviral therapy. VL ranged from undetectable-6.08 log10 using DBS and undetectable-6.40 log10 using plasma. The mean difference in VL (plasma-DBS) was 0.077 log10 (95%CI = 0.025-0.18 log10; standard deviation = 0.63 log10,). 78 (52%) DBS and 87 (58%) plasma samples had a VL>1000. Based on plasma 'gold-standard', DBS sensitivity for detection of VL>1000 was 87.4%, and specificity was 96.8%. CONCLUSION: There was generally good agreement between DBS and plasma VL for detection of VL>1000. Overall, finger prick DBS appeared to be an acceptable sample for classifying VL as above or below 1000 copies/mL using the NucliSENS assay.

Predictors of mortality in a cohort of HIV-1-infected adults in rural Africa.

BACKGROUND: CD4 cell count and plasma HIV RNA level are used to monitor HIV-infected patients in high-income countries, but the applicability in an African context with frequent concomitant infections has only been studied sparsely. Moreover, alternative inexpensive markers are needed in the attempts to roll out antiretroviral treatment in the region. We explored the prognostic strengths of classic and alternative progression markers in this study set in rural Zimbabwe. METHODS: We followed 196 treatment-naive HIV-1-infected patients from the Mupfure Schistosomiasis and HIV Cohort, Zimbabwe. CD4 cell count, HIV RNA level, hemoglobin (HB), total lymphocyte count (TLC), body mass index, clinical staging (Centers for Disease Control and Prevention [CDC] classification), and self-reported level of function (Karnofsky Performance Scale score) were assessed at baseline; participants were followed until death or last follow-up (3-4.3 years). RESULTS: All parameters except TLC predicted survival in univariate Cox models. HIV RNA level (P = 0.001), HB (P = 0.018), CD4 cell count (P = 0.047), and CDC category C (P = 0.007) remained significant in multivariate analysis. CONCLUSIONS: We found HIV RNA level and CD4 cell count to predict mortality with prognostic capabilities similar to findings from high-income countries. HB and clinical staging were strong independent predictors and might be considered candidates for alternative HIV progression markers.

Association of serum transferrin receptor concentration with markers of inflammation in Zimbabwean children.

BACKGROUND: Clinical studies have shown that degree of erythropoiesis, the hypoxic response, and iron status each independently influences transferrin receptor concentration, but there is conflicting information regarding the effect of inflammation on transferrin receptor expression. SUBJECTS AND METHODS: Levels of hemoglobin, reticulocytes, serum ferritin, transferrin receptors and inflammatory markers (C-reactive protein, interleukin-6 and neutrophils) were determined in 208 Zimbabwean children 10 ng/mL that adjusted for erythropoiesis with log(10) reticulocyte count, the hypoxic response with hemoglobin concentration and iron status with log(10) ferritin concentration, positive correlations were found between log(10) transferrin receptor concentration and log(10) C-reactive protein concentration (P=0.012), log(10) interleukin-6 concentration (P=0.011) and log(10) neutrophil count (P=0.013). These models predict that, with a baseline transferrin receptor concentration in the upper normal range of 8.0 mg/L and holding hemoglobin concentration and reticulocyte count constant, an increase from 1 to 10 mg/L in C-reactive protein is associated with a rise of 1.6 mg/L in transferrin receptor (95% C.I. 0.3-3.0 mg/L), an increase from 0.5-to-5.0 pg/mL in interleukin-6 with a rise of 1.9 mg/L (0.4-3.7 mg/L), and an increase from 2000 to 20,000/microL in neutrophil count with a rise of 3.6 mg/L (0.7-7.5 mg/L). CONCLUSION: Our results suggest that inflammation leads to an increase in circulating transferrin receptor concentration that is independent of the degree of erythropoiesis, the hypoxic response and iron status.

Schistosomiasis and HIV-1 infection in rural Zimbabwe: effect of treatment of schistosomiasis on CD4 cell count and plasma HIV-1 RNA load.

To determine whether treatment of schistosomiasis has an effect on the course of human immunodeficiency virus type 1 (HIV-1) infection, individuals with schistosomiasis and with or without HIV-1 infection were randomized to receive praziquantel treatment at inclusion or after a delay of 3 months; 287 participants were included in the study, and 227 (79%) were followed up. Among the 130 participants who were coinfected, those who received early treatment (n=64) had a significantly lower increase in plasma HIV-1 RNA load than did those who received delayed treatment (n=66) (P<.05); this difference was associated with no change in plasma HIV-1 RNA load in the early intervention group (P=.99) and an increase in plasma HIV-1 RNA load in the delayed intervention group (P<.01). Among the 227 participants who were followed up, those who received early treatment (n=105) had an increase in CD4 cell count, whereas those who received delayed treatment (n=122) did not (P<.05); this effect did not differ between participants when stratified by HIV-1 infection status (P=.17). The present study suggests that treatment of schistosomiasis can reduce the rate of viral replication and increase CD4 cell count in the coinfected host.

Effect of ferroportin Q248H polymorphism on iron status in African children.

BACKGROUND: Iron deficiency is common in African children, but genetic variations affecting susceptibility have not been identified. The Q248H mutation in ferroportin, a cellular iron exporter regulated by iron status and inflammation, may be associated with high iron stores in African adults. OBJECTIVE: The study examined the prevalence of iron deficiency in African children in an area where malaria transmission is low to absent and investigated whether ferroportin Q248H provides protection from iron deficiency. DESIGN: Complete blood counts, serum markers of iron status and inflammation, and ferroportin Q247H were measured in 208 preschool children in Harare, Zimbabwe. Iron deficiency was defined by serum ferritin and C-reactive protein (CRP) concentrations (definition 1) or by ferritin and the ratio of transferrin receptor to log10 ferritin (definition 2). RESULTS: Q248H was present in 40 children (38 heterozygotes, 2 homozygotes), elevated CRP was present in 26 (12.5%), and iron deficiency was present in 50 (24.0%) (definition 1) or 55 (26.4%) (definition 2). The interaction between ferroportin Q248H and CRP was significant for ferritin concentrations (P = 0.027) in a 2-factor analysis of variance model. With elevated CRP, the estimated geometric mean (SE range) ferritin concentration was 74 (52-106) microg/L for Q248H heterozygotes but 24 (20-30) microg/L for wild-type subjects (P = 0.016). With normal CRP, the ferritin concentration was 16 (14-19) microg/L whether or not the mutation was present. After adjustment for age and weight-for-height z score, the odds ratio (OR) for iron deficiency in Q248H heterozygotes was not significant according to definition 1 (OR: 0.53; 95% CI: 0.18, 1.40; P = 0.222) or definition 2 (OR: 0.39; 95% CI: 0.14, 1.07; P = 0.068). CONCLUSIONS: Any effect of Q248H in protecting against iron deficiency may be observable in children exposed to repeated inflammatory conditions. Further studies of iron status and ferroportin Q248H in African children are needed.