Is Antiretroviral Therapy Causing Long-Term Liver Damage? A Comparative Analysis of HIV-Mono-Infected and HIV/Hepatitis C Co-Infected Cohorts

The effects of highly active antiretroviral therapy (HAART) on progression of hepatic fibrosis in HIV-hepatitis C virus (HCV) co-infection are not well understood. Deaths from liver diseases have risen in the post-HAART era, yet some cross-sectional studies have suggested that HAART use is associated with improved fibrosis rates. In a retrospective cohort of 533 HIV mono-infected and 127 HIV/HCV co-infected patients, followed between January 1991 and July 2005 at a university-based HIV clinic, we investigated the relationship between cumulative HAART exposure and hepatic fibrosis, as measured by the aspartate aminotransferase-to-platelet ratio index (APRI). We used a novel methodological approach to estimate the dose-response relationship of the effect of HAART exposure on APRI. HAART was associated with increasing APRI over time in HIV/HCV co-infected patients suggesting that they may be experiencing cumulative hepatotoxicity from antiretrovirals. The estimated median change (95% confidence interval) in APRI per one year of HAART intake was of −0.46% (−1.61% to 0.71%) in HIV mono-infected compared to 2.54% (−1.77% to 7.03%) in HIV/HCV co-infected patients. Similar results were found when the direct effect of HAART intake since the last visit was estimated on the change in APRI. HAART use associated is with increased APRI in patients with HIV/HCV co-infection. Therefore treatment for HCV infection may be required to slow the growing epidemic of end-stage liver disease in this population

A systematic review and meta-analysis of studies evaluating the performance of point-of-care tests for human papillomavirus screening.

BACKGROUND: High-risk human papillomavirus (HPV) is a necessary cause of high-grade cervical intraepithelial neoplasia (grade 2 or higher, CIN2+). Simplified and rapid HPV DNA assays designed for use in resource-limited settings have recently become available. METHODS: We performed a systematic review and meta-analysis by searching Medline, Embase, Global Health and CINAHL databases for studies from 1 January 2004 to 25 February 2017 that reported the performance of careHPV or OncoE6 for the detection of histological CIN2+ in cervical cancer screening. We used bivariate models to estimate pooled sensitivity and specificity for CIN2+ and CIN3+. RESULTS: A total of 29 657 women were included from seven studies evaluating the performance of careHPV for the detection of CIN2+ and four studies among 27 845 women for the detection of CIN3+. The pooled prevalence for CIN2+ and CIN3+ was 2.3% and 1.1%, respectively. careHPV had sensitivity and specificity of 88.1% (95% CI 81.4 to 92.7) and 83.7% (95% CI 74.9 to 89.8), respectively, for CIN2+ and 90.3% (95% CI 83.4 to 94.5) and 85.3% (95% CI 73.1 to 92.5), respectively, for CIN3+, using clinician-collected cervical specimen. The corresponding pooled estimates using self-collected vaginal swabs were 73.6% (95% CI 64.9 to 80.8) and 88.0% (95% CI 79.1 to 93.5) for CIN2+ and 75.2% (95% CI 66.8 to 82.0) and 90.6% (95% CI 83.4 to 94.9) for CIN3+. Two studies using OncoE6 reported sensitivity and specificity ranging from 31.3% to 42.4% and 99.1%-99.4% for CIN2+, and 53.5% and 98.9% for CIN3+ for one study. CONCLUSION: CareHPV has good sensitivity and specificity for the detection of CIN2+ and CIN3+, but sensitivity was lower using self-collected vaginal samples. The specificity is lower in high HPV prevalence populations such as women living with HIV. OncoE6 assay warrants further evaluation

Clinical Prognostic Value of RNA Viral Load and CD4 Cell Counts during Untreated HIV-1 Infection—A Quantitative Review

Background: The prognostic value of CD4 counts and RNA viral load for identifying treatment need in HIV-infected individuals depends on (a) variation within and among individuals, and (b) relative risks of clinical progression per unit CD4 or RNA difference. Methodology/Principal Findings: We reviewed these measurements across (a) 30 studies, and (b) 16 cohorts of untreated seropositive adults. Median within-population interquartile ranges were 74,000 copies/mL for RNA with no significant change during the course of infection; and 330 cells/μL for CD4, with a slight proportional increase over infection. Applying measurement and physiological fluctuations observed on chronically infected patients, we estimate that 45% of population-level variation in RNA, and 25% of variation in CD4, were due to within-patient fluctuations. Comparing a patient with RNA at upper 75th centile with a patient at median RNA, 5-year relative risks were 1.4 (95% CI 1.2-1.7) for AIDS and 1.5 (1.3-1.9) for death, without change over the course of infection. In contrast, for a patient with CD4 count at the lower 75th centile, relative risks increased from 1.0 at seroconversion to maxima of 6.3 (4.4-8.9) for AIDS and 5.5 (2.7-10.1) for death by year 6, when the population median had fallen to 300 cells/ μL. Below 300 cells/μL, prognostic power did not increase, due to a narrower CD4 range. Conclusions: Findings support the current WHO recommendation (used with clinical criteria) to start antiretroviral treatment in low-income settings at CD4 thresholds of 200-350 cells/μL, without pre-treatment RNA monitoring - while not precluding earlier treatment based on clinical, socio-demographic or public health criteria

A survey on use of rapid tests and tuberculosis diagnostic practices by primary health care providers in South Africa: implications for the development of new point-of-care tests

BACKGROUND: Effective infectious disease control requires early diagnosis and treatment initiation. Point-of-care testing offers rapid turn-around-times, facilitating same day clinical management decisions. To maximize the benefits of such POC testing programs, we need to understand how rapid tests are used in everyday clinical practice. METHODS: In this cross-sectional survey study, 400 primary healthcare providers in two cities in South Africa were interviewed on their use of rapid tests in general, and tuberculosis diagnostic practices, between September 2012 and June 2013. Public healthcare facilities were selected using probability-sampling techniques and private healthcare providers were randomly selected from the Health Professional Council of South Africa list. To ascertain differences between the two healthcare sectors 2-sample z-tests were used to compare sample proportions. RESULTS: The numbers of providers interviewed were equally distributed between the public (n = 200) and private sector (n = 200). The most frequently reported tests in the private sector include blood pressure (99.5%), glucose finger prick (89.5%) and urine dipstick (38.5%); and in the public sector were pregnancy (100%), urine dipstick (100%), blood pressure (100%), glucose finger prick (99%) and HIV rapid test (98%). The majority of TB testing occurs in the public sector, where significantly more providers prefer Xpert MTB/RIF assay, the designated clinical TB diagnostic tool by the national TB program, as compared to the private sector (87% versus 71%, p-value >0.0001). Challenges with regard to TB diagnosis included the long laboratory turn-around-time, difficulty in obtaining sputum samples and lost results. All providers indicated that a new POC test for TB should be rapid and cheap, have good sensitivity and specificity, ease of sample acquisition, detect drug-resistance and work in HIV-infected persons. Conclusion/significance The existing centralized laboratory services, poor quality assurance, and lack of staff capacity deter the use of more rapid tests at POC. Further research into the practices and choices of these providers is necessary to aid the development of new POC tests

Respiratory Symptoms and Airway Obstruction in HIV-Infected Subjects in the HAART Era

Background: Prevalence and risk factors for respiratory symptoms and airway obstruction in HIV-infected subjects in the era of highly active antiretroviral therapy (HAART) are unknown. We evaluated respiratory symptoms and measured airway obstruction to identify the impact of HAART and other risk factors on respiratory symptoms and pulmonary function. Methodology/Principal Findings: Two hundred thirty-four HIV-infected adults without acute respiratory symptoms were recruited from an HIV clinic. All subjects were interviewed and performed spirometry. Multivariate linear and logistic regressions were performed to determine predictors of respiratory symptoms, forced expiratory volume in one second (FEV1) percent predicted, and FEV1/forced vital capacity (FEV1 / FVC). Thirty-one percent of subjects reported at least one respiratory symptom. Smoking status (current or former versus never) (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.41-5.22, p = 0.003), higher log plasma HIV viral levels (OR = 1.12, 95%CI = 1.02-1.24, p = 0.02), and lower FEV1/FVC (OR = 1.06 for every 0.01 decrease in FEV1/FVC, 95%CI = 1.02-1.14, p = 0.001) were independent predictors of respiratory symptoms. Age (p = 0.04), pack-year smoking history (p<0.001), previous bacterial pneumonia (p = 0.007), and HAART use (p = 0.04) were independent predictors of decreased FEV1/FVC. Conclusions/Significance: Respiratory symptoms remain common in HIV-infected subjects, especially in those with a smoking history. Subjects who were older, had a greater pack-year history of smoking, or previous bacterial pneumonia had lower FEV1/FVC ratios. Interestingly, use of HAART was independently associated with a decreased FEV1/FVC, possibly secondary to an immune response to subclinical infections, increased autoimmunity, or other factors associated with HAART use. © 2009 George et al

Impact of Round-the-Clock, Rapid Oral Fluid HIV Testing of Women in Labor in Rural India

Nitika Pant Pai and colleagues report the results of offering a round-the-clock rapid HIV testing program in a rural labor ward setting in India

Rapid and point-of-care tests for the diagnosis of Trichomonas vaginalis in women and men.

BACKGROUND: Trichomonasvaginalis (TV) is a highly prevalent parasitic infection worldwide. It is associated with many adverse reproductive health outcomes. Many infections are asymptomatic and syndromic management leads to underdetection of TV. Traditional methods of TV detection such as wet preparation are insensitive. New rapid, point-of-care (POC) tests can enhance the diagnosis of trichomoniasis. METHODS: The authors reviewed the literature and discuss older POC tests for TV detection, as well as the OSOM lateral flow test, the AmpliVue test, the Solana test and the GeneXpert test as well as the limitations of wet preparation and culture for detection of TV. RESULTS: The OSOM test is easy to perform, compared with other POC tests, and is Clinical Laboratory Improvement Amendments (CLIA)-waived, equipment-free, has sensitivities of 83%-86% compared with nucleic acid amplification tests (NAATs) and can be performed in 15 min. The AmpliVue and the Solana tests are not CLIA waived and require small pieces of equipment. They are molecular amplified assays and can be completed in <1 hour. AmpliVue demonstrated a sensitivity for vaginal swabs of 100% compared with wet preparation/culture and 90.7% compared with NAATs. Solana demonstrated a sensitivity of 98.6%-100% for vaginal swabs and 92.9%-98% for female urines, compared with wet preparation/culture. Compared with other NAATs, the sensitivity for Solana was 89.7% for swabs and 100% for urine. The GeneXpert TV test for women and men is a moderately complex test, requires a small platform and can be performed in <1 hour. The sensitivity compared with wet preparation/culture for self-collected vaginal swabs was 96.4%, 98.9% for endocervical specimens and 98.4% for female urine. For men, sensitivity for urines was excellent (97.2%). The specificity for all assays was excellent. CONCLUSIONS: Several rapid POC tests have the potential to rapidly diagnose trichomoniasis in women and one is available for detection of TV in men

Pilot Study of Essential Drug Quality in Two Major Cities in India

BACKGROUND: India is an increasingly influential player in the global pharmaceutical market. Key parts of the drug regulatory system are controlled by the states, each of which applies its own standards for enforcement, not always consistent with others. A pilot study was conducted in two major cities in India, Delhi and Chennai, to explore the question/hypothesis/extent of substandard and counterfeit drugs available in the market and to discuss how the Indian state and federal governments could improve drug regulation and more importantly regulatory enforcement to combat these drugs. METHODOLOGY/PRINCIPAL FINDINGS: Random samples of antimalarial, antibiotic, and antimycobacterial drugs were collected from pharmacies in urban and peri-urban areas of Delhi and Chennai, India. Semi-quantitative thin-layer chromatography and disintegration testing were used to measure the concentration of active ingredients against internationally acceptable standards. 12% of all samples tested from Delhi failed either one or both tests, and were substandard. 5% of all samples tested from Chennai failed either one or both tests, and were substandard. Spatial heterogeneity between pharmacies was observed, with some having more or less substandard drugs (30% and 0% respectively), as was product heterogeneity, with some drugs being more or less frequently substandard (12% and 7% respectively). CONCLUSIONS/SIGNIFICANCE: In a study using basic field-deployable techniques of lesser sensitivity rather than the most advanced laboratory-based techniques, the prevalence of substandard drugs in Delhi and Chennai is confirmed to be roughly in accordance with the Indian government's current estimates. However, important spatial and product heterogeneity exists, which suggests that India's substandard drug problem is not ubiquitous, but driven by a subset of manufacturers and pharmacies which thrive in an inadequately regulated environment. It is likely that the drug regulatory system in India needs to be improved for domestic consumption, and because India is an increasingly important exporter of drugs for both developed and developing countries. Some poor countries with high burdens of disease have weak drug regulatory systems and import many HIV/AIDS, tuberculosis and malaria drugs from India

Do digital innovations for HIV and sexually transmitted infections work? Results from a systematic review (1996-2017).

OBJECTIVE: Digital innovations with internet/mobile phones offer a potential cost-saving solution for overburdened health systems with high service delivery costs to improve efficiency of HIV/STI (sexually transmitted infections) control initiatives. However, their overall evidence has not yet been appraised. We evaluated the feasibility and impact of all digital innovations for all HIV/STIs. DESIGN: Systematic review. SETTING/PARTICIPANTS: All settings/all participants. INTERVENTION: We classified digital innovations into (1) mobile health-based (mHealth: SMS (short message service)/phone calls), (2) internet-based mobile and/or electronic health (mHealth/eHealth: social media, avatar-guided computer programs, websites, mobile applications, streamed soap opera videos) and (3) combined innovations (included both SMS/phone calls and internet-based mHealth/eHealth). PRIMARY AND SECONDARY OUTCOME MEASURES: Feasibility, acceptability, impact. METHODS: We searched databases MEDLINE via PubMed, Embase, Cochrane CENTRAL and Web of Science, abstracted data, explored heterogeneity, performed a random effects subgroup analysis. RESULTS: We reviewed 99 studies, 63 (64%) were from America/Europe, 36 (36%) from Africa/Asia; 79% (79/99) were clinical trials; 84% (83/99) evaluated impact. Of innovations, mHealth based: 70% (69/99); internet based: 21% (21/99); combined: 9% (9/99).All digital innovations were highly accepted (26/31; 84%), and feasible (20/31; 65%). Regarding impacted measures, mHealth-based innovations (SMS) significantly improved antiretroviral therapy (ART) adherence (pooled OR=2.15(95%CI: 1.18 to 3.91)) and clinic attendance rates (pooled OR=1.76(95%CI: 1.28, 2.42)); internet-based innovations improved clinic attendance (6/6), ART adherence (4/4), self-care (1/1), while reducing risk (5/5); combined innovations increased clinic attendance, ART adherence, partner notifications and self-care. Confounding (68%) and selection bias (66%) were observed in observational studies and attrition bias in 31% of clinical trials. CONCLUSION: Digital innovations were acceptable, feasible and generated impact. A trend towards the use of internet-based and combined (internet and mobile) innovations was noted. Large scale-up studies of high quality, with new integrated impact metrics, and cost-effectiveness are needed. Findings will appeal to all stakeholders in the HIV/STI global initiatives space