Mathematical models provide an understanding of in vivo replication kinetics of human immunodeficiency virus type 1 (HIV-1). With a novel intervention designed for increased potency, we have more accurately deduced the half-lives of virus-producing CD4؉ T cells, 0.7 day, and the generation time of HIV-1 in vivo, approximately 2 days, confirming the dynamic nature of HIV-1 replication.In 1996, we developed a mathematical model to analyze a set of plasma human immunodeficiency virus type 1 (HIV-1) RNA data from five chronically infected individuals treated with ritonavir monotherapy (5). On the basis of these results, we estimated the half-life (t 1/2 ) of free virions to be 0.24 day and the t 1/2 of productively infected CD4ϩ T cells to be 1.6 days. These turnover rates were considered minimum estimates because the analysis assumed that viral replication was completely suppressed by the therapy. From these data and measured baseline viral loads, we calculated minimal daily virion production to be ϳ10 10 particles in a typical patient. Moreover, the dynamic turnover of HIV-1 and productively infected cells formed the scientific rationale for combination antiretroviral therapy (1, 5), which has led to significant reductions in HIV-1-related morbidity and mortality (3).We have subsequently performed two additional experiments to better define c, the clearance rate constant of plasma virions. The results of these studies (6) allowed us to adjust the previous estimate for virion t 1/2 to a new value of ϳ30 min. Similarly, we have also adjusted the estimate for ␦, the rate of loss of productively infected CD4 ϩ T cells, in a follow-up study (4). The new estimate of the t 1/2 of virus-producing cells was ϳ1.1 days, again assuming that the combination antiretroviral therapy used was completely suppressive.Advances in the development of antiretroviral agents have yielded a number of drugs that are more effective in blocking HIV-1 replication in vivo (7). Thus, we have better tools in hand to readdress the issue of the relative potency of our therapeutic regimens and, hence, to better estimate ␦. As we have previously reported, the slope of the initial phase of plasma HIV-1 RNA decline depends on the degree of suppression of viral replication, as well as on ␦ (1, 4, 5). As the potency of combination therapy approaches 100%, the determination of ␦ becomes more precise. We now report findings from a Rockefeller University Institutional Review Board-approved novel interventional trial to reassess ␦, as well as the relative potency of our current antiretroviral therapies.Nine chronically HIV-1-infected individuals (Table 1) were treated with lopinavir-ritonavir (1,066 and 266 mg/day, respectively), efavirenz (600 mg/day), lamivudine (300 mg/day), and tenofovir DF (300 mg/day). Study subjects were hospitalized for the first 72 h of therapy, when plasma viral loads were measured by reverse transcription-PCR (Roche Amplicor Ultrasensitive Cobas 1.5; detection limit of 50 copies/ml) at 6-h intervals. Thereafter, measurements were ...

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Background: Female patients have historically received less aggressive lipid management than male patients. Contemporary care patterns and the potential causes for these differences are unknown. Methods and Results: Examining the Patient and Provider Assessment of Lipid Management Registry—a nationwide registry of outpatients with or at risk for atherosclerotic cardiovascular disease—we compared the use of statin therapy, guideline-recommended statin dosing, and reasons for undertreatment. We specifically analyzed sex differences in statin treatment and guideline-recommended statin dosing using multivariable logistic regression. Among 5693 participants (43% women) eligible for 2013 American College of Cardiology/American Heart Association Cholesterol Guideline–recommended statin treatment, women were less likely than men to be prescribed any statin therapy (67.0% versus 78.4%; P <0.001) or to receive a statin at the guideline-recommended intensity (36.7% versus 45.2%; P <0.001). Women were more likely to report having previously never been offered statin therapy (18.6% versus 13.5%; P <0.001), declined statin therapy (3.6% versus 2.0%; P <0.001), or discontinued their statin (10.9% versus 6.1%; P <0.001). Women were also less likely than men to believe statins were safe (47.9% versus 55.2%; P <0.001) or effective (68.0% versus 73.2%; P <0.001) and more likely to report discontinuing their statin because of a side effect (7.9% versus 3.6%; P <0.001). Sex differences in both overall and guideline-recommended intensity statin use persisted after adjustment for demographics, socioeconomic factors, clinical characteristics, patient beliefs, and provider characteristics (adjusted odds ratio, 0.70; 95% CI, 0.61–0.81; P <0.001; and odds ratio, 0.82; 95% CI, 0.73–0.92; P <0.01, respectively). Sex differences were consistent across primary and secondary prevention indications for statin treatment. Conclusions: Women eligible for statin therapy were less likely than men to be treated with any statin or guideline-recommended statin intensity. A combination of women being offered statin therapy less frequently, while declining and discontinuing treatment more frequently, accounted for these sex differences in statin use.