Stigma impedes AIDS prevention

Thirty years since the first cases of AIDS were described, there is much to celebrate regarding progress in the treatment and prevention of the disease. Within the past year alone, several studies have revealed that antiretroviral drugs can prevent the sexual transmission of HIV. Yet worldwide, many people who are potentially exposed to the virus avoid finding out whether they carry it, or deny that they are at risk of contracting it. Unless people establish whether they are infected, they will not be able to be adopt the most appropriate preventive measures. As scientists and clinicians, our ability to overcome this denialism will determine whether we ultimately succeed in using combinations of all the preventive and therapeutic tools now available to slow, and eventually stop, the HIV/AIDS pandemic

Unsustainability of a measles immunisation campaign - rise in measles incidence within 2 years of the campaign

The 1990 national mass measles immunisation campaign resulted in a marked reduction in measles incidence in Natal/KwaZulu in the first 6 months after the campaign. Data from the measles ward admissions book at Clairwood Hospital were collated for the period 1 January 1989 to 31 May 1992 to assess the sustainability of the effects of the campaign. For the first 12 months after the campaign, measles admissions were consistently low. Thereafter, the number increased steadily, rising sharply to above precampaign levels 21 months after the campaign. The age distribution of measles patients indicated that the initial fall in the 10 - 12-month age group had been reversed in the second year after the campaign, suggesting that the high vaccination coverage achieved for this age group during the campaign had not been maintained. Measles admissions to Clairwood Hospital indicate that the effect of the measles imInunisation campaign has not been sustained and that urgent action is required to avert a possible epidemic.S Afr Med J 1993; 83: 322-323

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

MTN-001: Randomized Pharmacokinetic Cross-Over Study Comparing Tenofovir Vaginal Gel and Oral Tablets in Vaginal Tissue and Other Compartments

Background: Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development. Objective: MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design. Methods and Findings: We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ≥90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ≥130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03). Conclusions: Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir's antiviral effect substantially influence PrEP efficacy. Trial Registration: ClinicalTrials.gov NCT00592124

Synthesis and Cytotoxicity Screening of Some Novel Benzofuranoyl-pyrazole Derivatives against Liver and Cervix Carcinoma Cell Lines

A series of new pyrazole, thiazole and thiazolinone derivatives incorporated into benzofuran were synthesized by using 3-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-carboxaldehyde as starting material. A total of 41 novel compounds were synthesized. Some of these synthesized compounds were evaluated for cytotoxicity activity against HEPG2 (liver carcinoma cell line) and HELA (cervix carcinoma cell line). The tested compounds (1, 2c, 7c, 8b, 9b, 13b and 14b) showed better activities at low concentration against the commonly used human carcinoma cell lines. A detailed synthesis, spectroscopic data and cytotoxicity screening for the new compounds are described.Keywords: Pyrazole, thiazolinone, benzofuran, benzofuranoyl-pyrazoles, cytotoxic screening, HEPG2, HELAPDF and Supplementry file attache

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Performance of swabs, lavage, and diluents to quantify biomarkers of female genital tract soluble mucosal mediators

Background: Measurement of immune mediators and antimicrobial activity in female genital tract secretions may provide biomarkers predictive of risk for HIV-1 acquisition and surrogate markers of microbicide safety. However, optimal methods for sample collection do not exist. This study compared collection methods. Methods: Secretions were collected from 48 women (24 with bacterial vaginosis [BV]) using vaginal and endocervical Dacron and flocked swabs. Cervicovaginal lavage (CVL) was collected with 10 mL of Normosol-R (n = 20), saline (n = 14), or water (n = 14). The concentration of gluconate in Normosol-R CVL was determined to estimate the dilution factor. Cytokine and antimicrobial mediators were measured by Luminex or ELISA and corrected for protein content. Endogenous anti-HIV-1 and anti-E. coli activity were measured by TZM-bl assay or E. coli growth. Results: Higher concentrations of protein were recovered by CVL, despite a 10-fold dilution of secretions, as compared to swab eluents. After protein correction, endocervical swabs recovered the highest mediator levels regardless of BV status. Endocervical and vaginal flocked swabs recovered significantly higher levels of anti-HIV-1 and anti-E. coli activity than Dacron swabs (P<0.001). BV had a significant effect on CVL mediator recovery. Normosol-R tended to recover higher levels of most mediators among women with BV, whereas saline or water tended to recover higher levels among women without BV. Saline recovered the highest levels of anti-HIV-1 activity regardless of BV status. Conclusions: Endocervical swabs and CVL collected with saline provide the best recovery of most mediators and would be the optimal sampling method(s) for clinical trials. © 2011 Dezzutti et al

Comparison of treatment outcomes of new smear-positive pulmonary tuberculosis patients by HIV and antiretroviral status in a TB/HIV clinic, Malawi

Background: Smear-positive pulmonary TB is the most infectious form of TB. Previous studies on the effect of HIV and antiretroviral therapy on TB treatment outcomes among these highly infectious patients demonstrated conflicting results, reducing understanding of important issues. Methods: All adult smear-positive pulmonary TB patients diagnosed between 2008 and 2010 in Malawi's largest public, integrated TB/HIV clinic were included in the study to assess treatment outcomes by HIV and antiretroviral therapy status using logistic regression. Results: Of 2,361 new smear-positive pulmonary TB patients, 86% had successful treatment outcome (were cured or completed treatment), 5% died, 6% were lost to follow-up, 1% failed treatment, and 2% transferred-out. Overall HIV prevalence was 56%. After adjusting for gender, age and TB registration year, treatment success was higher among HIV-negative than HIV-positive patients (adjusted odds ratio 1.49; 95% CI: 1.14-1.94). Of 1,275 HIV-infected pulmonary TB patients, 492 (38%) received antiretroviral therapy during the study. Pulmonary TB patients on antiretroviral therapy were more likely to have successful treatment outcomes than those not on ART (adjusted odds ratio: 1.83; 95% CI: 1.29-2.60). Conclusion: HIV co-infection was associated with poor TB treatment outcomes. Despite high HIV prevalence and the integrated TB/HIV setting, only a minority of patients started antiretroviral therapy. Intensified patient education and provider training on the benefits of antiretroviral therapy could increase antiretroviral therapy uptake and improve TB treatment success among these most infectious patients. © 2013 Tweya et al

Informed consent for HIV cure research in South Africa: issues to consider

Background: South Africa has made great progress in the development of HIV/AIDS testing, treatment and prevention campaigns. Yet, it is clear that prevention and treatment campaigns alone are not enough to bring this epidemic under control. Discussion: News that the “Berlin patient” and the “Mississippi baby” have both been “cured” of HIV brought hope to people living with HIV/AIDS in South Africa that a cure for HIV/AIDS is within reach. Despite the recent setbacks announced in the “Mississippi Baby” case, protocols aimed at curing HIV/AIDS are being developed in South Africa. However with evidence to suggest that participants in clinical trials do not understand the basic concepts in the informed consent process, there is concern that future participants in HIV/AIDS cure research will lack comprehension of the basic elements of future clinical trials that aims to cure HIV/AIDS and confuse research with clinical care. Summary: Research ethics committees have an important role to play in ensuring that participants understand the basic concepts discussed in the informed consent process, that they understand that research is not clinical care and they are unlikely to benefit from any early phase trials seeking to cure HIV/AIDS

Effects of river water and salinity on the toxicity of deltamethrin to freshwater shrimp, cladoceran, and fish

Deltamethrin is a pyrethroid insecticide used extensively to control invertebrate pests on cotton and other crops. It is acutely toxic to nontarget aquatic organisms, but existing toxicity data are mostly from toxicity tests using purified laboratory water that differs greatly from the turbid, high-conductivity rivers in the cotton-growing regions of Australia. The aim of this study was to determine whether the water quality variables conductivity, suspended particles, and dissolved organic matter alter the toxicity of deltamethrin to freshwater crustaceans and a fish. We tested three Australian native species: a cladoceran (Ceriodaphnia cf. dubia), a freshwater shrimp (Paratya australiensis), and larvae of the eastern rainbow fish (Melanotaenia duboulayi). Conductivity of the test solutions ranged from 200 to 750 μS/cm, but such changes did not modify the toxicity of deltamethrin to any of the test species. However, the toxicity of deltamethrin to C. cf. dubia and P. australiensis in river water was significantly decreased (1.8-fold to 6.3-fold reduction) compared to that in laboratory water. Variability in the toxicity data limited our ability to detect differences between laboratory and river water for M. duboulayi. Despite reductions in toxicity in natural waters, deltamethrin remained highly toxic [all L(E)C50 values <0.26 μg/L] to all organisms tested; thus, further investigation of the hazard of deltamethrin is warranted. © 2008 Springer Science+Business Media, LLC