Incidence of stage 3 chronic kidney disease and progression on tenofovir-based regimens.

OBJECTIVE: To describe the incidence of rapid kidney function decline (RKFD), and stage 3 chronic kidney disease (CKD) in HIV-1-infected adults initiated on tenofovir-containing antiretroviral therapy. METHODS: A retrospective cohort study at the infectious diseases clinic of Tygerberg Academic Hospital in Cape Town, South Africa. Patients with more than 3 ml/min per year decline in estimated glomerular filtration were classified as having RKFD, and stage 3 CKD was defined as a value less than 60 ml/min per 1.73 m. We used logistic and Cox proportional hazards regression models to determine factors associated with RKFD and stage 3 CKD. RESULTS: Of 650 patients, 361 (55%) experienced RKFD and 15 (2%) developed stage 3 CKD during a median interquartile range follow-up time of 54 (46.6-98) weeks. For every 10-year increase in age and 10 ml/min lower baseline estimated glomerular filtration, the odds of RKFD increased by 70% [adjusted odds ratio = 1.70, 95% confidence interval (CI) 1.36-2.13] and 57% (adjusted odds ratio = 1.57, 95% CI 1.38-1.80), respectively. Each 10-year older age was associated with a 1.90-fold increased risk of developing stage 3 CKD (adjusted hazard ratio = 1.90, 95% CI: 1.10-3.29). Women had about four-fold greater risk of stage 3 CKD compared with men (adjusted hazard ratio = 3.96, 95% CI: 1.06-14.74). CONCLUSION: About half of our study population developed RKFD but only 2% progressed to stage 3 CKD. Approaches that provide balanced allocation of limited resources toward screening and monitoring for kidney dysfunction and HIV disease management are critically needed in this setting.

Combination antiretroviral therapy reduces the detection risk of cervical human papilloma virus infection in women living with HIV.

OBJECTIVE: Data on the effect of combination antiretroviral therapy (cART) on cervical human papilloma virus (HPV) infection are both limited and conflicting. We aimed to determine the effect of the initiation of cART for HPV genotype detection on cervical samples in HIV-infected South African women. DESIGN: Prospective cohort study. METHODS: Generalized estimating equation was performed to estimate parameters of mixed-effects logistic regression models of cART on HPV cervical detection risk, adjusting for time-dependent covariates CD4 T-cell count, sexual activity and excision treatment. Ratio of odds ratios (ORs) was computed to compare the pooled cART effect on lower vs. high-risk HPV genotype groups, to the effect of cART on the risk of HPV-16 detection. RESULTS: Of the 300 patients, 204 (68%) were commenced on ART during follow-up, as they met the criteria for cART initiation. cART significantly reduced the risk for detection of HPV by 77% [OR 0.23, 95% confidence interval (CI) 0.15-0.37]. cART significantly reduced the risk of HPV-16 detection (OR 0.50, 95% CI 0.37-0.67). Every month on cART significantly reduced the detection risk of any HPV type by 9% (OR 0.91, 95% CI 0.89-0.94). The protective effect of cART on the detection risk for the low-risk HPV genotype group was significantly less than the protective effect of cART on the detection risk of HPV-16 (ratio of ORs 1.35, 95% CI 1.22-1.50). CONCLUSION: cART significantly reduced cervical HPV infection. This effect was dependent on the duration of exposure to cART and is the mechanism by which cART may improve the outcome of dysplasia in HIV-infected women.

Targeting HIV: past, present and future.

Since the identification of the human immunodeficiency virus (HIV) as the cause of the syndrome of acquired immunodeficiency syndrome (AIDS), there has been an evolution of compounds targeting the replication of the virus in an effort to delay clinical progression. In this review, we revise the mechanism of action of the different groups of drugs. We shortly revisit the older and perhaps lesser used as well as the more recently approved drugs and mention some of the compounds still under investigation.

Evaluation of paradoxical TB-associated IRIS with the use of standardized case definitions for resource-limited settings.

OBJECTIVE: Standardized case definitions have recently been proposed by the International Network for the Study of HIV-associated immune reconstitution inflammatory syndrome (INSHI; [IRIS]) for use in resource-limited settings. We evaluated paradoxical tuberculosis (TB)-associated IRIS in a large cohort from a TB endemic setting with the use of these case definitions. DESIGN: A retrospective cohort study. METHOD: We reviewed records from 1250 South African patients who initiated antiretroviral therapy (ART) over a 5-year period. RESULTS: A total of 333 (27%) of the patients in the cohort had prevalent TB at the initiation of ART. Of 54 possible paradoxical TB-associated IRIS cases, 35 fulfilled the INSHI case definitions (11% of TB cases). CONCLUSIONS: INSHI-standardized case definitions were used successfully in identifying paradoxical TB-associated IRIS in this cohort and resulted in a similar proportion of TB IRIS cases (11%) as that reported in previous studies from resource-limited settings (8%-13%). This case definition should be evaluated prospectively.

Novel mutations and SNPs identified in CCR2 using a new comprehensive denaturing gradient gel electrophoresis assay.

A single nucleotide polymorphism (SNP) at codon 64 in the CC chemokine receptor 2 gene (CCR2 V64I) has been associated with a dominant effect of delaying disease progression from human immunodeficiency virus-1 (HIV-1) infection to acquired immunodeficiency syndrome (AIDS). The objective of our study was to design a comprehensive mutation detection assay for the entire coding region of the CCR2A and CCR2B gene transcripts, including all relevant splice site junctions and to identify novel mutations and SNPs within our predominantly African-based population, which could influence an individual's susceptibility to HIV-1 infection and/or progression to AIDS. The mutation detection assay, based on denaturing gradient gel electrophoresis (DGGE), allowed for the complete analysis of five individuals per denaturing gel. Our study cohort consisted of 102 HIV seropositive patients and 144 HIV seronegative controls from the diverse South African population. Application of the CCR2-DGGE assay resulted in the detection of two previously reported CCR2 polymorphisms, namely CCR2 V64I and CCR2 N260N, and 11 novel mutations, including seven SNPs occurring at high allelic frequencies within specific population groups of South Africa. The large number of novel mutations/SNPs identified, using the CCR2-DGGE assay, indicates the importance for comprehensive analysis of all candidate genes in host susceptibility to HIV-1 infection, specifically in the under-studied African-based populations.