By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates; Section Editor, HIV, is Associate Editor for Infectious Disease Alert.

Vaginal Microbicide Successful in Early Trials

Source: Keller MJ, et al. J Infect Dis. 2006;193:27–35.

An effective vaginal (or anal/ penile) microbicide could substantially diminish the risk of transmission of HIV, especially in the developing world where condom use has not gained uniform acceptance. Even if 20% of women used an agent with 60% activity against HIV for half of their sexual interactions, it is estimated that 2.5 million cases of HIV would be prevented in 3 years. Sadly, nonoxynol-9 proved too inflammatory with repeated applications to be of value.

A newer synthetic naphthalene sulfonic acid polymer, PRO 2000 gel (Indevus Pharmaceuticals, Lexington, MA), has been well-tolerated in Phase I clinical trials and is effective, at least, in vitro, against HIV and HSV. The agent interacts with glycoproteins to prevent entry of virus into cells. Studies show no evidence of systemic absorption when used intravaginally, and levels in vaginal secretions were significantly in excess of target concentrations 12 hours after application for either the 0.5% or 4% formulations. In a Phase I clinical trial conducted in India, 57% of female participants had at least one adverse event with twice daily applications for 2 weeks, including genitourinary complaints in 14% and intermenstrual bleeding in 12%. There were no serious adverse events, and the product was generally well tolerated.

For men, penile applications appear to be similarly well tolerated, although preliminary data suggests there may be some resistance to its use. I suspect making the product more palatable may be important.

These authors randomized 25 HIV positive women to receive active gel or placebo. Patients were screened and treated for pre-existing STDs and UTIs. Cervical lavage specimens were obtained 48 hrs before and 1 hr after intravaginal application of study drug. The specimens were then treated with a cocktail of antibiotics to prevent bacterial overgrowth, diluted to varying concentrations, and spiked with HIV-1 and HSV-2. (Spiking of specimens was necessary because the levels of HIV RNA in the cervical secretions of many of these women were too low to be adequately studied.)

More than 1000-fold decrease in HIV and HSV viral replication was observed in specimens obtained from women following active gel use compared with pre-treatment specimens or controls. HIV viral load was reduced 4.03 logs for the active gel group compared with 0.25 in the placebo group (P < .001). Similarly, HSV viral load fell 3.09 logs in the active gel group compared with a decline of 0.64 logs for the placebo group compared with pre-treatment levels.

There was no apparent difference in inflammatory activity as measured by cytokine response between the 2 groups, an important finding, as inflammatory changes may counter-balance the antimicrobial effects of a product (similar to nonoxynol-9). Whether the gel will remain sufficiently active in the presence of semen during sex remains to be determined, but PRO 2000 gel appears to be a promising candidate for further study.

Highly Resistant MTB Fatal in HIV

Source: Pro-MED mail posts, September 1, September 4, and October 18, 2006.

A new, highly resistant strain of Mycobacterium tuberculosis has established a foot-hold in South Africa. The strain, dubbed "XDR-TB," is resistant to at least 8 TB agents and possibly more. Details were not available, but an initial report, presented at the International AIDS Conference in Toronto in August 2006, indicated that from January 2005 to March 2006, a total of 536 positive TB sputum cultures were obtained from 1540 patients in KwaZulu-Natal. While MDR-TB was identified in 41% of positive cultures from this rural area of South Africa, XDR-TB was found in 10% (!). Typing confirmed that 90% of the XDR strains were genetically similar. This preliminary report indicated that 52 of 53 persons died from their XDR-TB infection, all of whom were HIV positive. Following collection of sputum specimens, the median duration of survival was only 25 days.

More recent data confirm this strain has now been identified in 9 different provinces in South Africa, including KwaZulu-Natal, North West, Gauteng, Eastern Cape and Limpopo. At least 106 people have been infected and 74 are reported dead. Nosocomial transmission may be an important contributing factor, as infection control and isolation practices are not commonly available. The increased prevalence of HIV infection in these areas contributed to the high rate of mortality.

Diabetes in Modern Air Travel

Source: Burnett J.C., et al. J Travel Med. 2006;13:255–260.

These authors in Aberdeen queried 493 insulin-using diabetics presenting for routine care at the diabetes center regarding their experiences traveling abroad within the previous 12 months. Surprisingly, nearly two-thirds had some kind of air travel abroad in the previous year. Nearly half (44%) had traveled once or twice in the previous 12 months, and 24% had traveled > 10 times. The patients were grouped into those with short air flights (< 4 hrs) or long-haul flights (> 4 hrs).

One-tenth of each group experienced hypoglycemia either during the flight or within 24 hrs of arrival. Delays in air travel departure and landing times occurred in nearly one-third of subjects. While 91% carried some food with them during their flight, 10% reported problems with meals, including delays in obtaining meals and difficulty obtaining a pre-ordered diabetic tray. Of those with hypoglycemia, 31% were severe and required assistance. Unfortunately, in order to compensate for the possibility of hypoglymia, many travelers reported deliberately experiencing hyperglycemia. This was 10-times more likely to be reported by individuals with long-haul flights.

While most insulin-using diabetics traveled with a companion or informed the airline staff they were using insulin, fully 15% told no one they were using insulin. Less than half had sought medical advice about managing their diabetes during travel.

Air travel has just gotten harder, and with the latest restriction on food/fluids on board, except when declared medically necessary, I suspect many travelers with medical illness may experience more frequent problems. During a recent flight from San Francisco to Toronto, no meals were served, although a snack of Oreo cookies, granola bars, and cheddar fish crackers was available for $5, hardly a healthy snack, especially for someone with diabetes. The authors suggest that diabetes clinics consider incorporating travel advice into their routine diabetes education. Pre-printed educational pamphlets for diabetics, even for short flights, may be useful.

Influenza A Responds to Tamiflu®Better Than Influenza B

Source: Kawai N, et al. Clin Infect Dis. 2006:43:439–444.

To evaluate the effectiveness of oseltamivir for influenza, oseltamivir was administered to 1818 patients with Influenza A and 1485 patients with Influenza B, all of whom were being seen in an "usual clinical setting" in 9 different community clinics in Japan. The patients were grouped by age and by time of onset of fever to the time of administration of the first dose of oseltamivir. A small number of patients who did not take drug were used as a comparator group.

Not surprisingly, patients who received no treatment had a significantly longer duration of fever compared with treated patients with Influenza A (82 hrs vs 48 hrs) or Influenza B (78 hrs vs 65 hrs, respectively) (both groups, P < 0.001). The duration of fever after receipt of the drug was similar regardless of age or the timing of the first dose of drug, with one exception. Patients aged 7–15 years had a somewhat shorter duration of illness, although this difference was arguably not clinically significant (~4 hrs).

What was somewhat surprising was the finding that for those who received treatment, the duration of fever following administration of oseltamivir was significantly shorter for patients with Influenza A compared to those with Influenza B. This statistically significant difference was found for all age groups, regardless of the timing of administration. For example, comparing patients with Influenza A or B, the mean duration of fever after receipt of the first dose of oseltamivir was 32 hrs vs 48 hrs, respectively, for those who received the drug within 0–12 hrs. Similarly, the mean duration of fever after the 1st dose of oseltamivir patients with Influenza A vs Influenza B was 32 hrs and 45 hrs, respectively, for those who received the drug within 27–48 hrs of onset of symptoms.

In addition, isolation of virus at the completion of treatment was significantly more frequent in patients with Influenza B than Influenza A (52% vs 16%, P < 0.001).

These data confirm that oseltamivir is more effective against infection with Influenza A vs Influenza B, although the difference may not be especially clinically meaningful.