Genital secretion HIV RNA shedding in HIV-positive patients on ritonavir-boosted protease inhibitor monotherapy or standard combination ART: a cross-sectional sub-study from the PIVOT Trial.

BACKGROUND: Protease inhibitors (PI) have relatively low penetration into the genital tract, raising concerns about the potential for genital HIV RNA shedding in patients taking PI-based regimens, particularly PI monotherapy (PI-mono). METHODS: We measured HIV RNA and PI drug concentrations in samples of semen, cervico-vaginal and rectal mucosa secretions, and plasma in patients after 48-96 weeks on PI-mono or standard triple therapy. RESULTS: A total of 85 participants were recruited. Of the 43 participants on PI-mono (70% on darunavir [DRV]/ritonavir [r]), 3 had detectable virus in semen or vaginal secretions (all below quantification limit), and none in rectal mucosa or plasma. Among those taking triple therapy, five had detectable virus in semen or vaginal secretions (HIV RNA >50 copies/ml in one), none in rectal mucosa and one in plasma. The median (IQR) concentration of DRV and atazanavir in semen (659.7 [339-1,089] and 128.8 [63-368] ng/ml, respectively) and cervico-vaginal samples (2,768 [312-7,879] and 1,836 [359-3,314] ng/ml, respectively) exceeded their protein adjusted median inhibition concentration (MIC50). DRV concentration in rectal secretions showed higher variability compared with concentration in the other sites, with particularly high rectal secretion/blood ratios (median 8.4, IQR 2.6-68.7:1). CONCLUSIONS: We found no substantive evidence of HIV shedding in patients taking PI-mono, suggesting that PIs provide adequate control of virus in the genital compartment and are unlikely to lead to ongoing sexual transmission.

Effects of glucose ingestion on autonomic and cardiovascular measures during rest and mental challenge.

BACKGROUND: High levels of dietary sugar consumption may result in dysregulated glucose metabolism and lead to elevated cardiovascular disease risk via autonomic nervous system and cardiovascular dysfunction. Altered cardiovascular function can be examined using perturbation tasks such as mental challenge. This study examined the effects of controlled glucose intake on cardiovascular measures at rest and in responses to mental challenge in a laboratory setting. METHOD: Using a double blind within-subjects design, participants were monitored at baseline, following ingestion of a glucose or taste-control solution, during structured speech (SS), anger recall (AR) and recovery (N=24, 288 repeated measures; age = 21±2 years). Pre-ejection period (PEP), heart rate (HR), stroke index (SI), cardiac index (CI), blood pressure and total peripheral resistance (TPR) were measured throughout the protocol. RESULTS: Glucose resulted in sustained decreased PEP levels compared to control condition (Δ=11.98±9.52 vs. 3.27±7.65 m·s, P<.001) and transient increases in resting HR (P=.011), CI (P=.040) and systolic blood pressure (P=.009). Glucose did not result in increased cardiovascular reactivity to mental challenge tasks, but was associated with a delayed HR recovery following AR (P=.032). CONCLUSION: Glucose intake resulted in a drop in PEP indicating increased sympathetic nervous system activity. No evidence was found for glucose-related exaggerated cardiovascular responses to mental challenge. Dysregulated glucose metabolism may result in elevated cardiovascular disease risk as a result of repeated glucose-induced elevations of sympathetic nervous system activity.

Flavor-nutrient learning is less rapid with fat than with carbohydrate in rats.

Flavor-nutrient learning occurs when the post-ingestive consequences of a food are associated with its flavor. As a signal of the food's energy density, flavor-nutrient associations have the potential to contribute to the regulation of meal size. While all calorie sources (fat, carbohydrate, protein, ethanol) can support flavor-nutrient learning, prior research has found that flavor-nutrient associations based on fat may require higher nutrient concentrations and more rigorous experimental protocols than are required to train carbohydrate (cho)-based associations. To further explore potential macronutrient-specific differences in flavor-nutrient learning, the present study compared the time course of acquisition of cho- and fat-based associations. Rats were trained to associate distinctive flavors with high-density (3.2 kcal/mL) and low-density (0.2 kcal/mL) orally-consumed solutions, either fat (corn oil emulsion) or carbohydrate (sucrose). For each nutrient, both within- and between-group designs were used to assess (via two-bottle preference testing) whether flavor-nutrient learning had occurred after 2, 4, or 6 training trial pairs. Rats trained with carbohydrate demonstrated preferential intake of the low-density paired flavor after only 2 training pairs; in contrast, rats trained with fat required 6 training pairs. These findings demonstrate differential rapidity of acquisition flavor-nutrient associations. The longer time course of acquisition of fat-based flavor-nutrient associations may be yet another mechanism by which high-fat foods promote overeating.

B safe, B sorted: results of a hepatitis B vaccination outreach programme.

The risk of hepatitis B among men having sex with men (MSM) is high, with core antibody rates ranging from 5% to 81%. We describe an outreach, hepatitis B vaccination programme aiming to raise awareness of hepatitis B and increase vaccination uptake. The 13-week programme used an ultra rapid vaccination schedule. Follow-up was defined as complete if the client was core antibody positive, had adequate surface antibody levels following prior vaccination or received three vaccine doses. One hundred and fifty clients were screened for hepatitis B and syphilis. Three cases of untreated syphilis (early latent) and one case of e-antigen-positive hepatitis B were detected. With the aid of text-message reminders, a vaccination completion rate of 76.6% was achieved, with 82.5% completing follow-up. In conclusion, this programme succeeded in reaching MSM not routinely accessing services. Text messaging was an acceptable and effective method of follow-up, resulting in high vaccination completion rates.

The influence of antiretroviral therapy on the uptake of HIV testing in Tutume, Botswana.

This paper describes how the national antiretroviral (ARV) programme in Botswana has influenced the willingness of the community of Tutume District, Botswana to come forward for HIV testing. A retrospective review of Tutume Primary Hospital records was performed for three different periods: prior to the national antiretroviral therapy (ART) programme, once ART was available in limited centres and once ART was available locally. There was a five-fold increase in the number of HIV tests performed once treatment became available locally, primarily due to female voluntary testing. Access to free ART increases the HIV testing rate of previously reluctant communities.

Meal size of high-fat food is reliably greater than high-carbohydrate food across externally-evoked single-meal tests and long-term spontaneous feeding in rat.

A series of studies in rat using isoenergetic (kcal/ml) liquid diets differing in fat content has previously found dietary fat to dose-dependently increase daily caloric intake. In single-meal tests in which meal initiation was externally evoked in feeding-associated environments, the behavioral expression of this overeating was found to be larger meal intake. The present studies confirmed the ecological validity of this larger meal size of high-fat diet (HF) relative to high-carbohydrate diet (HC): meal size of HF>HC in home-cage testing (Experiment 1), and during undisturbed, spontaneous feeding in which ingestive behavior was continuously monitored (Experiments 2 and 3). These findings demonstrate that single-meal paradigms yield results consistent with spontaneous feeding of high-fat and high-carbohydrate liquid diets, thus supporting the use of single-meal studies to better understand the physiological bases of elevated caloric intake associated with chronic consumption of a high-fat diet.

Independent effects of diet palatability and fat content on bout size and daily intake in rats.

Although considerable evidence attests to the hyperphagic effects of high-fat (HF) diets, the attribute(s) of these diets (e.g., palatability, caloric density, and postingestive effects) which promote overeating is still unclear. The present studies investigated the independent effects of diet palatability and macronutrient composition on intake using the self-regulated intragastric infusion paradigm. In Experiment 1, rats were infused with either HF or high-carbohydrate (HC) diet while drinking either saccharin (Sacc) or a more palatable saccharin-glucose (SaccGlu) test solution for 9 days. HF elicited greater daily intake than HC; lick pattern analysis revealed that HF produced larger but not more frequent bouts. Test solution was not related to intake, possibly due to the relatively modest palatability manipulation. Experiment 2 provided a more sensitive test: The palatability manipulation was strengthened and diet infusion made optional by provision of chow. HF again elicited larger bout size and total daily intake (diet+chow) than HC. Rats given the more palatable solution significantly increased intake (via larger bouts) and thus the amount of diet infused, but chow intake decreased such that total kilocalorie intake was not significantly related to solution palatability. The reliable observation that HF promoted larger bout size and greater total kilocalorie intake than HC provides additional evidence that fat sends weaker feedback signals relevant to controls of both satiation (suppression of ongoing eating, behaviorally manifest in meal size) and satiety (suppression of subsequent intake, reflected in total daily intake).

Dietary fat dose dependently increases spontaneous caloric intake in rat.

OBJECTIVE: To characterize the dose-response relationship between dietary fat to carbohydrate ratio and spontaneous caloric intake. RESEARCH METHODS AND PROCEDURES: Male Long-Evans rats consumed milk-based liquid diets that differed in fat content (17% to 60% of kilocalories) but had equivalent protein content and energy density. In Experiment 1, rats consumed one of the diets (n = 9/diet group) as the sole source of nutrition for 16 days. In Experiment 2, diets were offered as an option to nutritionally complete chow for 4 days followed by a 3-day chow-only washout in a randomized within-subjects design (n = 30). In Experiment 3, nine rats received isocaloric intragastric infusions of diet overnight, with chow available ad libitum. At least two no-infusion days separated the different diet infusions, which were given in random order. Food intake was measured daily RESULTS: Dietary fat dose dependently increased total daily kilocalories in each of the three paradigms. DISCUSSION: These data imply that the postingestive effects of carbohydrate and fat differentially engage the physiological substrates that regulate daily caloric intake. These findings reiterate the importance of investigating macronutrient-specific controls of feeding, rather than prematurely concluding that dietary attributes that covary with fat content (e.g., caloric density and palatability) drive the overeating associated with a high-fat diet.

Dietary fat content affects energy intake and weight gain independent of diet caloric density in rats.

Recent considerations of high-fat diet hyperphagia have focused on fat's relatively high energy density as the critical variable which promotes overeating. However, a high-fat (HF) diet has been shown to enhance intake and weight gain relative to a high-carbohydrate (HC) diet when both energy density and palatability are equated [Am. J. Physiol. 269 (1995) R30]. The present studies investigated the generality of this finding across manipulations of diet caloric density, diet physical form, and chow availability. Separate groups of male rats were fed HF or HC at either 2.3 or 1.15 kcal/ml for 16 days; HF feeding enhanced weight gain relative to HC across both levels of energy density. HF hyperphagia also occurred when diets were presented in semisolid (gelled) form, and when chow was available in addition to liquid diet. These findings are consistent with previous observations that an HF diet can enhance daily kilocalorie intake and weight gain at least partly via a mechanism that is unrelated to caloric density.