HLA-G 3' untranslated region 14-base pair deletion: association with poor survival in an HIV-1-infected Zimbabwean population.

We aimed to evaluate whether the HLA-G 14-base pair (bp) polymorphism (rs16375) has an impact on human immunodeficiency virus HIV progression and survival in an antiretroviral therapy-naive Zimbabwean cohort (n = 312). Rs16375 was genotyped using a competitive allele-specific polymerase chain reaction system; CD4 cell counts and HIV RNA were measured with flow cytometry and commercially available polymerase chain reaction; survival was followed up for 4.3 years. The homozygous HLA-G -14-bp genotype is associated with higher viral load (P = .004), lower CD4 cell count (P = .01), and increased mortality (hazard ratio, 1.9; 95% confidence interval, 1.033-3.522; P = .04) compared with HLA-G +14-bp carriers.

Schistosomiasis and HIV in rural Zimbabwe: efficacy of treatment of schistosomiasis in individuals with HIV coinfection.

BACKGROUND: There is evidence from experimental models that the praziquantel-induced clearance of schistosomiasis is dependent on the host's immune response. Consequently, human immunodeficiency virus (HIV)-related immunodeficiency may impair the effect of praziquantel treatment. METHODS: In a prospective cohort study, schistosome-infected subjects who were or were not coinfected with HIV were treated with praziquantel and followed up 3, 6, and 12 months after treatment. Quantitative measures of intensity of schistosomiasis (egg counts and levels of circulating anodic antigen in serum) and immunodeficiency (CD4+ cell counts and viral loads) were collected. RESULTS: Cure rates based on egg counts 3 months after treatment were satisfactory and were similar for HIV-positive individuals (cure rate, 86%) and HIV-negative individuals (cure rate, 85%); the magnitude of decrease in egg count was equal. Cure rates based on circulating anodic antigen levels were much lower than cure rates based on egg counts, with HIV-positive individuals experiencing significantly less clearance of schistosomiasis (cure rate, 31%) than HIV-negative individuals (cure rate, 52%), whereas the magnitude of decrease in circulating anodic antigen was also lower among HIV-positive individuals (P < .01). CONCLUSION: The effect of praziquantel may be limited to affecting the fecundity of adult schistosomes in the immunocompromised host, thus reducing egg excretion while leaving schistosomes metabolically active, as shown by the fact that levels of antigen production are maintained. Special guidelines for treatment of schistosomiasis in HIV-coinfected individuals may need to be developed.

Polymorphisms in the interleukin-7 receptor α gene and mortality in untreated HIV-infected individuals.

OBJECTIVES: Recently, polymorphisms in the gene encoding the interleukin-7 receptor α (IL7Rα) have been shown to influence the CD4 cell count in HIV-infected individuals. The objective of this study was to examine the impact of 10 single nucleotide polymorphisms (SNPs) in or in close proximity to the IL7Rα on mortality among 152 untreated HIV infected in a Zimbabwean cohort. METHODS: Patients were followed prospectively, median time of follow-up 3.9 year. SNPs were genotyped using competitive allele-specific PCR. Cox regression was used for survival analyses. RESULTS: We found an increased mortality among carriers of the IL7Rα, rs6897932, T-allele (hazard ratio: 2.56 [95% confidence interval (CI) 1.22-5.35], P=0.013). This association remained significant after adjusting for age, sex, baseline HIV-RNA and baseline CD4 cell count (hazard ratio=2.36 (95% CI 1.06-2.58), P=0.036). CONCLUSION: The results suggest an association between the IL7Rα, rs6897932, T-allele and increased mortality among untreated HIV-infected, Zimbabwean individuals.

Association of HIV and ART with cardiometabolic traits in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in SSA populations. METHODS: We conducted a systematic review and meta-analysis through MEDLINE and EMBASE (up to January 2012), as well as direct author contact. Eligible studies provided summary or individual-level data on one or more of the following traits in HIV+ and HIV-, or ART+ and ART- subgroups in SSA: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs) and fasting blood glucose (FBG) or glycated hemoglobin (HbA1c). Information was synthesized under a random-effects model and the primary outcomes were the standardized mean differences (SMD) of the specified traits between subgroups of participants. RESULTS: Data were obtained from 49 published and 3 unpublished studies which reported on 29 755 individuals. HIV infection was associated with higher TGs [SMD, 0.26; 95% confidence interval (CI), 0.08 to 0.44] and lower HDL (SMD, -0.59; 95% CI, -0.86 to -0.31), BMI (SMD, -0.32; 95% CI, -0.45 to -0.18), SBP (SMD, -0.40; 95% CI, -0.55 to -0.25) and DBP (SMD, -0.34; 95% CI, -0.51 to -0.17). Among HIV+ individuals, ART use was associated with higher LDL (SMD, 0.43; 95% CI, 0.14 to 0.72) and HDL (SMD, 0.39; 95% CI, 0.11 to 0.66), and lower HbA1c (SMD, -0.34; 95% CI, -0.62 to -0.06). Fully adjusted estimates from analyses of individual participant data were consistent with meta-analysis of summary estimates for most traits. CONCLUSIONS: Broadly consistent with results from populations of European descent, these results suggest differences in cardiometabolic traits between HIV-infected and uninfected individuals in SSA, which might be modified by ART use. In a region with the highest burden of HIV, it will be important to clarify these findings to reliably assess the need for monitoring and managing cardiometabolic risk in HIV-infected populations in SSA.

CCL3L gene copy number and survival in an HIV-1 infected Zimbabwean population.

The C-C motif chemokine ligand 3-like (CCL3L) protein is a potent chemoattractant which by binding to C-C chemokine receptor type 5 (CCR5) inhibits human immunodeficiency virus (HIV) entry. Copy number variation (CNV) of the CCL3L has been shown to be associated with HIV susceptibility and progression to AIDS, but these results have been inconsistent. We examined a Zimbabwean study population for an association of CCL3L CNV with HIV status, progression (CD4 T-cells and viral load), and survival. Another aim was to investigate the possible effects of CCL3L CNV on CCL3 protein concentration. A treatment-naïve cohort, which included 153 HIV infected and 159 HIV uninfected individuals, was followed for up to 4.3 years. The CNV of the CCL3L was determined by duplex real-time polymerase chain reaction. We found no association between four CCL3L CNV strata and HIV status (P=0.7), CD4 T-cell count (P=0.9), viral load (P=0.9), or CCL3 protein levels (P=1.0). Survival among the HIV infected individuals did not differ according to CCL3L copy number. In this cohort, CCL3L CNV did not affect HIV status, pathogenesis, or survival.

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.

Schistosomiasis and HIV-1 infection in rural Zimbabwe: implications of coinfection for excretion of eggs.

BACKGROUND: Stunted development and reduced fecundity of Schistosoma parasites in immunodeficient mice and the impaired ability of human immunodeficiency virus 1 (HIV-1)-infected humans to excrete schistosome eggs have been described. This study explores the effect that HIV-1-associated immunodeficiency has on the excretion of schistosome eggs in a large cohort of coinfected individuals. METHODS: In a cross-sectional survey, urine and stool samples were obtained from and HIV-1 status was determined for 1545 individuals. More extensive data, including quantitative measures of intensity of infection in schistosomiasis and immunodeficiency, were collected in the Mupfure schistosomiasis and HIV longitudinal cohort, composed of 379 participants of whom 154 were coinfected with HIV-1 and Schistosoma parasites. RESULTS: In the cross-sectional survey, the overall prevalence of schistosomiasis was 43.4%, and 26.3% of the participants were infected with HIV-1. Schistosome infections were due to Schistosoma haematobium in 63.6% of cases, S. mansoni in 18.1% of cases, and dual infections in 18.4% of cases. Intensities of Schistosoma infections, measured by the number of eggs excreted and by the level of circulating anodic antigens, did not differ between HIV-1-negative and HIV-1-positive participants coinfected with S. haematobium, S. mansoni, or both. CD4 cell counts were significantly lower in HIV-1-positive participants and in S. mansoni-infected HIV-1-negative participants than in other participants. CONCLUSION: The present study suggests that adult HIV-1-related immunodeficiency does not impair the ability to excrete eggs in low-intensity infection with S. haematobium, S. mansoni, or both and that infection with HIV-1 may not have major implications for diagnosis and surveillance of schistosomiasis.

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.