Swift GRBs and the blast wave model

The complex structure of the light curves of Swift GRBs has made their interpretation and that of the blast wave caused by the burst, more difficult than in the pre-Swift era. We aim to constrain the blast wave parameters: electron energy distribution, p, density profile of the circumburst medium, k, and the continued energy injection index, q. We do so by comparing the observed multi-wavelength light curves and X-ray spectra of a Swift sample to the predictions of the blast wave model. We can successfully interpret all of the bursts in our sample of 10, except two, within the framework of the blast wave model, and we can estimate with confidence the electron energy distribution index for 6 of the sample. Furthermore we identify jet breaks in half of the bursts. A statistical analysis of the distribution of p reveals that, even in the most conservative case of least scatter, the values are not consistent with a single, universal value. The values of k suggest that the circumburst density profiles are not drawn from only one of the constant density or wind-like media populations.Comment: 6 pages, submitted to the proceedings of the 6th Huntsville GRB Symposium (2008

Differential effects of acyclovir and 9-(1,3-dihydroxy-2-propoxymethyl)guanine on herpes simplex virus and Epstein-Barr virus in a dually infected human lymphoblastoid cell line.

We investigated the effects of acyclovir and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) on a lymphoblastoid cell line dually infected with Epstein-Barr virus and herpes simplex virus (HSV) type 1. The numbers of Epstein-Barr virus genomes were reduced during 70 days of treatment with either drug. Both drugs suppressed HSV replication in a dose-related manner. In the continued presence of the drugs, HSV developed resistance, rapidly to acyclovir and much more slowly to 30 microM DHPG. Analysis of HSV glycoprotein C production and viral DNA showed that treatment with 100 microM DHPG eliminated HSV production, curing the cell line of HSV persistent infection

Atovaquone Compared with Dapsone for the Prevention of Pneumocystis carinii Pneumonia in Patients with HIV Infection Who Cannot Tolerate Trimethoprim, Sulfonamides, or Both

BACKGROUND Patients with human immunodeficiency virus (HIV) infection and latent tuberculosis are at substantial risk for the development of active tuberculosis. As a public health measure, prophylactic treatment with isoniazid has been suggested for HIV-infected persons who have anergy and are in groups with a high prevalence of tuberculosis. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial of six months of prophylactic isoniazid treatment in HIV-infected patients with anergy who have risk factors for tuberculosis infection. The primary end point was culture-confirmed tuberculosis. RESULTS The study was conducted from November 1991 through June 1996. Over 90 percent of the patients had two or more risk factors for tuberculosis infection, and nearly 75 percent of patients were from greater New York City. After a mean follow-up of 33 months, tuberculosis was diagnosed in only 6 of 257 patients in the placebo group and 3 of 260 patients in the isoniazid group (risk ratio, 0.48; 95 percent confidence interval, 0.12 to 1.91; P=0.30). There were no significant differences between the two groups with regard to death, death or the progression of HIV disease, or adverse events. CONCLUSIONS Even in HIV-infected patients with anergy and multiple risk factors for latent tuberculosis infection, the rate of development of active tuberculosis is low. This finding does not support the use of isoniazid prophylaxis in high-risk patients with HIV infection and anergy unless they have been exposed to active tuberculosis

Seek, test, treat: substance-using women in the HIV treatment cascade in South Africa

Abstract Background Women in South Africa who use alcohol and other drugs face multiple barriers to HIV care. These barriers make it difficult for women to progress through each step in the HIV treatment cascade from diagnosis to treatment initiation and adherence. This paper examines correlates of HIV status, newly diagnosed HIV status, and use of antiretroviral therapy (ART). Methods Outreach workers recruited sexually active Black African women who used substances in Pretoria as part of a U.S. National Institutes of Health-funded geographically clustered randomized trial examining the effect of an intervention to reduce alcohol and drug use as well as sexual risk behaviors. To address the question of interest in the current investigation, cross-sectional baseline data were used. At study enrollment, all participants (N = 641) completed an interview, and underwent rapid HIV testing and biological drug screening. Those who tested positive for HIV and were eligible for ART were asked about their barriers to initiating or adhering to ART. Bivariate and multivariable logistic regression analyses were conducted to determine correlates of HIV status, newly diagnosed HIV, and ART use. Results At enrollment, 55% of participants tested positive for HIV, and 36% of these women were newly diagnosed. In multivariable analyses of the entire sample, women who had completed 10th grade were less likely to be living with HIV (OR 0.69; CI 0.48, 0.99) and those from the inner city were more likely to be living with HIV (OR 1.83; CI 1.26, 2.67). Among HIV-positive participants, women were less likely to be newly diagnosed if they had ever been in substance abuse treatment (OR 0.15; CI 0.03, 0.69) or used a condom at last sex (OR 0.58; CI 0.34, 0.98) and more likely to be newly diagnosed if they were physically assaulted in the past year (OR 1.97; CI 1.01, 3.84). Among women eligible for ART, fewer were likely to be on treatment (by self-report) if they had a positive urine test for opiates or cocaine (OR 0.27; CI 0.09, 0.80). Conclusions These results, although cross-sectional, provide some guidance for provincial authorities to address barriers to HIV care for sexually active, substance-using vulnerable women in Pretoria. Targeting the inner city with prevention campaigns, expanding and improving substance abuse treatment programs, linking clients with simultaneous HIV testing and treatment, and targeting women who have experienced sexual assault and violence may help the government achieve the UNAIDS 90-90-90 treatment target. Clinical Trials.gov NCT01497405 registered on December 1, 2011

The biobehavioral Women’s Health CoOp in Pretoria, South Africa: study protocol for a cluster-randomized design

Abstract Background South Africa has 6.4 million adults over the age of 15 living with HIV. Gender inequality issues continue to drive the HIV epidemic in South Africa, where Black African women bear the greatest HIV burden. Limited access to services; little capacity to negotiate sex and condom use; and other legal, social, and economic inequities make women highly vulnerable to HIV infection. Behavioral interventions have been shown to decrease risk behaviors, but they have been less successful in reducing HIV incidence. Conversely, biomedical prevention strategies have proven to be successful in reducing HIV incidence, but require behavioral interventions to increase uptake and adherence. Consequently, there is a need for integrated approaches that combine biomedical and behavioral interventions. Effective combination prevention efforts should comprise biomedical, behavioral, and structural programming proven in randomized trials that focuses on the driving forces and key populations at higher risk of HIV infection and transmission. Methods/Design This prospective, geographically clustered randomized field experiment is enrolling participants into two arms: a control arm that receives standard HIV testing and referral for treatment; and an intervention arm that receives an evidence-based, woman-focused behavioral intervention that emphasizes risk reduction and retention, the Women’s Health CoOp. We divided the city of Pretoria into 14 mutually exclusive geographic zones and randomized these zones into either the control arm or the intervention arm. Outreach workers are recruiting drug-using women from each zone. At baseline, eligible participants complete a questionnaire and biological testing for HIV, recent drug use, and pregnancy. Follow-up interviews are completed at 6 and 12 months. Discussion The biobehavioral intervention in this study merges an efficacious behavioral HIV prevention intervention for women with biomedical prevention through HIV treatment as prevention using a Seek, Test, Treat and Retain strategy. This combination biobehavioral intervention is designed to (1) improve the quality of life and reduce HIV infectiousness among women who are HIV positive, and (2) reduce HIV risk behaviors among women regardless of their HIV status. If efficacious, this intervention could help control the HIV epidemic in South Africa. Trial registration Trial registration no: NCT01497405

Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding

The objective of this study is to determine whether detection of HIV infection was delayed in infants exposed to antiretroviral prophylaxis to prevent HIV transmission during breastfeeding

Use of Lipid-Based Nutrient Supplements by HIV-Infected Malawian Women during Lactation Has No Effect on Infant Growth from 0 to 24 Weeks

The Breastfeeding, Antiretrovirals, and Nutrition Study evaluated the effect of daily consumption of lipid-based nutrient supplements (LNS) by 2121 lactating, HIV-infected mothers on the growth of their exclusively breast-fed, HIV-uninfected infants from 0 to 24 wk. The study had a 2 × 3 factorial design. Malawian mothers with CD4+ ≥250 cells/mm3, hemoglobin ≥70 g/L, and BMI ≥17 kg/m2 were randomized within 36 h of delivery to receive either no LNS or 140 g/d of LNS to meet lactation energy and protein needs, and mother-infant pairs were assigned to maternal antiretroviral drugs (ARV), infant ARV, or no ARV. Sex-stratified, longitudinal, random effects models were used to estimate the effect of the 6 study arms on infant weight, length, and BMI. Logistic regression models were used to calculate the odds of growth faltering [decline in weight-for-age Z-score (WAZ) or length-for-age Z-score (LAZ) >0.67] using the control arm as the reference. Although some differences between study arms emerged with increasing infant age in boys, there were no consistent effects of the maternal supplement across the 3 growth outcomes in longitudinal models. At the ages where differences were observed, the effects on weight and BMI were quite small (≤200 g and ≤0.4 kg/m2) and unlikely to be of clinical importance. Overall, 21 and 34% of infants faltered in WAZ and LAZ, respectively. Maternal supplementation did not reduce the odds of infant weight or length faltering from 0 to 24 wk in any arm. These results indicate that blanket supplementation of HIV-infected lactating women may have little impact on infant growth

CD4 count outperforms World Health Organization clinical algorithm for point-of-care HIV diagnosis among hospitalised HIV-exposed Malawian infants

To determine, for the WHO algorithm for point-of-care diagnosis of HIV infection, the agreement levels between pediatricians and non-physician clinicians, and to compare sensitivity and specificity profiles of the WHO algorithm and different CD4 thresholds against HIV PCR testing in hospitalized Malawian infants

Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi

ABSTRACT Cytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIV-exposed infants in Malawi and correlated the results with the presence of detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2,369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth and at 24 and 48 weeks of age. Ninety-four of 127 infants (74.0%) tested at 24 weeks of age had CMV IgG of low or intermediate avidity, signifying primary CMV infections. An additional 22 infants (17.3%) had IgG of high avidity; 19 of them had CMV DNA detected in their blood, indicating infant infections. Taken together, these results show that the estimated prevalence of CMV infection at 24 weeks was 88.9%. By 48 weeks of age, 81.3% of infants had anti-CMV IgG; most of them (70.9%) had IgG of high avidity. The CMV serology and avidity testing, combined with the PCR results, confirmed a high rate of primary CMV infection by 6 months of life among breastfeeding infants of HIV-infected mothers. The CMV PCR in blood detected most, but not all, infant CMV infections

Atovaquone Compared with Dapsone for the Prevention of Pneumocystis carinii Pneumonia in Patients with HIV Infection Who Cannot Tolerate Trimethoprim, Sulfonamides, or Both

BACKGROUND Although trimethoprim–sulfamethoxazole is the drug of choice for the prevention of Pneumocystis carinii pneumonia, many patients cannot tolerate it and must switch to an alternative agent. METHODS We conducted a multicenter, open-label, randomized trial comparing daily atovaquone (1500-mg suspension) with daily dapsone (100 mg) for the prevention of P. carinii pneumonia among patients infected with the human immunodeficiency virus who could not tolerate trimethoprim–sulfamethoxazole. The median follow-up period was 27 months. RESULTS Of 1057 patients enrolled, 298 had a history of P. carinii pneumonia.P. cariniipneumonia developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compared with 135 of 521 in the dapsone group (18.4 cases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence interval, 0.67 to 1.09; P=0.20). The relative risk of death was 1.07 (95 percent confidence interval, 0.89 to 1.30; P=0.45), and the relative risk of discontinuation of the assigned medication because of adverse events was 0.94 (95 percent confidence interval, 0.74 to 1.19; P=0.59). Among the 546 patients who were receiving dapsone at base line, the relative risk of discontinuation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confidence interval, 2.37 to 6.01; P CONCLUSIONS Among patients who cannot tolerate trimethoprim–sulfamethoxazole, atovaquone and dapsone are similarly effective for the prevention ofP. carinii pneumonia. Our results support the continuation of dapsone prophylaxis among patients who are already receiving it. However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred choice for prophylaxis against P. cariniipneumonia