Hormonal contraceptive methods and risk of HIV acquisition in women : a systematic review of epidemiological evidence

Peer reviewedPublisher PD

Effectiveness and safety of 30 mg versus 40 mg stavudine regimens: a cohort study among HIV-infected adults initiating HAART in South Africa

<p>Abstract</p> <p>Background</p> <p>As stavudine remains an important and widely prescribed drug in resource-limited settings, the effect of a reduced dose of stavudine (from 40 mg to 30 mg) on outcomes of highly active antiretroviral therapy (HAART) remains an important public health question.</p> <p>Methods</p> <p>We analyzed prospectively collected data from the Themba Lethu Clinic in Johannesburg, South Africa. We assessed the relationship between stavudine dose and six- and/or 12-month outcomes of stavudine substitution, failure to suppress viral load to below 400 copies/ml, development of peripheral neuropathy, lipoatrophy and hyperlactatemia/lactic acidosis. Since individuals with a baseline weight of less than 60 kg were expected to have received the same dose of stavudine throughout the study period, analysis was restricted to individuals who weighed 60 kg or more at baseline. Data were analyzed using logistic regression.</p> <p>Results</p> <p>Between 1 April 2004 and 30 September 2009, 3910 patients were initiated on antiretroviral therapy (ART) with a recorded stavudine dose and were included in the analysis. Of these, 2445 (62.5%) received a 40 mg stavudine dose while 1565 (37.5%) received 30 mg. In multivariate analysis, patients receiving a 40 mg dose were more likely to discontinue stavudine use (adjusted odds ratio, OR 1.71; 95% confidence limits, CI 1.13-2.57) than those receiving 30 mg by 12 months on ART. Additionally, patients receiving 40 mg doses of stavudine were more likely to report peripheral neuropathy (OR 3.12; 95% CI 1.86-5.25), lipoatrophy (OR 11.8; 95% CI 3.2-43.8) and hyperlactatemia/lactic acidosis (OR 8.37; 95% CI 3.83-18.29) in the same time period. Failure to suppress HIV viral load within 12 months of HAART initiation was somewhat more common among those given 40 mg doses (OR 1.62; 95% CI 0.88, 2.97) although this result lacked precision. Sensitivity analyses accounting for death and loss to follow up generally supported these estimates.</p> <p>Conclusions</p> <p>Lower stavudine dosage is associated with fewer reports of several stavudine-associated adverse events and also a lower risk of stavudine discontinuation within the first year on ART.</p

Notes on two-parameter quantum groups, (II)

This paper is the sequel to [HP1] to study the deformed structures and representations of two-parameter quantum groups $U_{r,s}(\mathfrak{g})$ associated to the finite dimensional simple Lie algebras \mg. An equivalence of the braided tensor categories \O^{r,s} and \O^{q} is explicitly established.Comment: 21 page

Comment on Williamson et al. (OpenSAFELY): The Table 2 Fallacy in a Study of COVID-19 Mortality Risk Factors

To the Editor: We write with respect to the recently published work by Williamson et al. “OpenSAFELY: factors associated with COVID-19 death in 17 million patients.” We have serious concerns about both the way these results are presented, and how they are likely to be interpreted. Our specific concerns revolve around whether the work is intended by the authors to estimate causal effects, or not—and how, regardless of their intent, it seems likely to us that their work will be interpreted as causal

Long term outcomes of antiretroviral therapy in a large HIV/AIDS care clinic in urban South Africa: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Clinical, immunologic and virologic outcomes at large HIV/AIDS care clinics in resource poor settings are poorly described beyond the first year of highly active antiretroviral treatment (HAART). We aimed to prospectively evaluate long-term treatment outcomes at a large scale HIV/AIDS care clinic in South Africa.</p> <p>Methods</p> <p>Cohort study of patients initiating HAART between April 1, 2004 and March 13, 2007, and followed up until April 1, 2008 at a public HIV/AIDS care clinic in Johannesburg, South Africa. We performed time to event analysis on key treatment outcomes and program impact parameters including mortality, retention in care, CD4 count gain, virologic success and first line regimen durability.</p> <p>Results</p> <p>7583 HIV-infected patients initiated care and contributed to 161,000 person months follow up. Overall mortality rate was low (2.9 deaths per 100 person years, 95% CI 2.6-3.2), but high in the first three months of HAART (8.4 per 100 person years, 95% CI 7.2-9.9). Long-term on-site retention in care was relatively high (74.4% at 4 years, 95%CI 73.2-75.6). CD4 count was above 200 cells/mm³after 6 months of treatment in almost all patients. By the fourth year of HAART, the majority (59.6%, 95%CI 57.8-61.4) of patients had at least one first line drug (mainly stavudine) substituted. Women were twice as likely to experience drug substitution (OR 1.97, 95% CI 1.80-2.16). By 6 months of HAART, 90.8% suppressed virus below 400 copies. Among those with initial viral suppression, 9.4% (95% CI 8.5-10.3%) had viral rebound within one year of viral suppression, 16.8% (95% CI 15.5-18.1) within 2 years, and 20.6% (95% CI 18.9-22.4) within 3 years of initial suppression. Only 10% of women and 13% of men initiated second line HAART.</p> <p>Conclusion</p> <p>Despite advanced disease presentation and a very large-scale program, high quality care was achieved as indicated by good long-term clinical, immunologic and virologic outcomes and a low rate of second line HAART initiation. High rates of single drug substitution suggest that the public health approach to HAART could be further improved by the use of a more durable first line regimen.</p

Can the new CKD-EPI BTP-B2M formula be applied in children?

Although measuring creatinine to determine kidney function is currently the clinical standard, new markers such as beta-trace protein (BTP) and beta-2-microglobulin (B2M) are being investigated in an effort to measure glomerular filtration rate more accurately. In their recent publication, Inker et al. (Am J Kidney Dis 2015; 67:40–48) explored the use of these two relatively new markers in combination with some commonly available clinical characteristics in a large cohort of adults with chronic kidney disease. Their research led them to develop three formulae using BTP, B2M, and a combination of the two. The combined formula is particularly attractive as it removes all gender bias, which applies to both serum creatinine and cystatin C. Using data from a cohort of 127 pediatric patients from our center, we sought to determine whether these formulae would be equally as effective in children as in adults. Unfortunately, we found that the formulae cannot be applied to the pediatric population

How subgroup analyses can miss the trees for the forest plots: A simulation study

Objectives: Subgroup analyses of clinical trial data can be an important tool for understanding when treatment effects differ across populations. That said, even effect estimates from prespecified subgroups in well-conducted trials may not apply to corresponding subgroups in the source population. While this divergence may simply reflect statistical imprecision, there has been less discussion of systematic or structural sources of misleading subgroup estimates. Study Design and Setting: We use directed acyclic graphs to show how selection bias caused by associations between effect measure modifiers and trial selection, whether explicit (e.g., eligibility criteria) or implicit (e.g., self-selection based on race), can result in subgroup estimates that do not correspond to subgroup effects in the source population. To demonstrate this point, we provide a hypothetical example illustrating the sorts of erroneous conclusions that can result, as well as their potential consequences. We also provide a tool for readers to explore additional cases. Conclusion: Treating subgroups within a trial essentially as random samples of the corresponding subgroups in the wider population can be misleading, even when analyses are conducted rigorously and all findings are internally valid. Researchers should carefully examine associations between (and consider adjusting for) variables when attempting to identify heterogeneous treatment effects