Abstract
HIV
A Pharmacological Explanation for Mixed PrEP Trial Results
Researchers in the Schools of Medicine and Pharmacy at the University of North Carolina, Chapel Hill, showed a large discrepancy in the tissue levels of two antiretroviral agents commonly used for pre-exposure prophylaxis (PrEP), and they have proposed that this variation in the drug levels and duration of action of PrEP agents may explain the conflicting results of PrEP clinical trials. During the past 2 years, seven prevention trials have yielded either successful and quite promising results, including nearly complete prevention of HIV transmission when viremia was suppressed, or failure to prevent HIV transmission. Poor adherence and inconsistent use of PrEP agents could have contributed to these outcomes, as failure to take the drugs everyday could lead to large variations in detectable drug levels in plasma and mucus membrane tissues that are key entry points for HIV transmission.
This study assessed the levels of two drugs used in PrEP, tenofovir (TFV) and emtricitabine (FTC)—administered together in a single daily dose of TDF/FTC (Truvada) to healthy subjects—in plasma and in genital secretions. The active intracellular phosphorylated metabolites of the drugs were measured in rectal, vaginal, and cervical tissue samples. The researchers found that the concentration of FTC over 24 h to 14 days in genital secretions was 27-fold greater than in blood plasma, whereas the concentration of TFV was only 2.5-fold greater in genital secretions compared to plasma. The concentrations of TFV and its metabolite were detectable in rectal tissue throughout the 14-day study period and were 100-fold higher than the concentrations in vaginal and cervical tissues. In contrast, FTC concentrations in vaginal and cervical tissues were 10- to 15-fold higher than in rectal tissue, but the FTC metabolite was only detectable in all three tissue types for 2 days after subjects received the drug. The study authors conclude that drug concentration in tissues may impact effectiveness, and this factor may help explain the recent clinical trial results.
Sources: Patterson KB, et al. Penetration of tenofovir and emtricitabine in mucosal tissues; Implications for prevention of HIV-1 transmission. Sci Transl Med 2011;3:112–114 and Kashuba A, et al. Pre-exposure prophylaxis for HIV prevention: how to predict success. The Lancet December 7, 2011; doi:10.1016/S0140-6736(11)61852-7.
Non-Targeted HIV Screening in EDs Not Efficient Strategy
In the U.S., about 20% (240,000) of the 1.2 million people infected with HIV do not know they carry the virus. One proposed, controversial strategy for identifying undiagnosed HIV cases worldwide is to perform non-targeted HIV screening in Emergency Departments (EDs). A group of researchers tested this approach in 29 EDs in Paris, which accounts for about half of the new HIV cases diagnosed annually in France. During a 6-week period, adult subjects who were able to provide consent were offered a fingerstick whole-blood HIV rapid test. Of the 12,754 patients tested, 18 (0.14%) received new HIV diagnoses. Nearly all (17 of 18) of those with a new diagnosis belonged to a high-risk group, 12 had been previously tested, and 8 were either symptomatic or had a CD4 count less than 350/μl, indicating late-stage infection. The authors concluded that although non-targeted HIV testing of the general population in EDs was feasible, “our findings do not support the implementation” of this approach. On a positive note, 12 of the 18 individuals with new HIV diagnoses were linked to care.
Source: d'Almeida KW, et al. for the Emergency Department HIV-Screening Group. Modest public health impact of nontargeted human immunodeficiency virus screening in 29 Emergency Departments. Arch Intern Med October 24, 2011; doi:10.1001/archinternmed.2011.535.
Steps for Improving HIV Care
The Centers for Disease Control and Prevention (CDC) reports that many people with HIV do not receive the medical care they need to reduce their viral load and stay healthy longer, reduce the chances of transmitting the virus to others, and benefit from prevention counseling. According to the CDC, only 28% of people with HIV know they are infected, get regular medical care, take antiretroviral therapy, and have HIV virus levels under control. Furthermore, less than half (45%) of people with HIV who do get medical care receive prevention counseling from their health care providers. Regular HIV care should include prevention counseling, providing STD testing and treatment services, drug rehabilitation, assistance in notifying partners, housing assistance, financial assistance and related services, and information and guidance on how to reduce viral load and slow or prevent progression to AIDS and how to prevent transmission of the virus to others.
Source: Center for Disease Control and Prevention. “Vital Signs: IV prevention through care and treatment—United States.” MMWR 2011;60:1618–1623.
HIV Risk Behavior Data for MSM
Of the approximately 1.1 million people in the United States who are living with HIV infection, more than half are men who have sex with men (MSM). Study data from the National HIV Behavioral Surveillance (NHBS) System collected during the 6-month period June to December 2008 show that MSM in the U.S. continue to engage in sexual and drug-use behaviors that increase their risk for acquiring HIV infection. The data analyzed represent more than 8,000 MSM who reported having at least one male sex partner. In addition, 14% of the subjects had at least one female sex partner during the previous 12 months. More than half of the participants (54%) reported having unprotected anal intercourse with a male partner: 37% had unprotected anal sex with a main male partner (with some level of commitment); and 25% had unprotected anal sex with a casual male partner. During the previous 12-month period, 46% of participants reported noninjection drug use, while 2% had injected drugs for nonmedical purposes.
In addition to risk behavior, the study also evaluated prevention and testing behavior. In the study population of MSM, 90% had been tested for HIV during their lifetime and 62% had been tested during the past 12 months. Furthermore, 51% had received a hepatitis vaccination and 35% had been tested for syphilis. Participation in an individual or group HIV behavioral intervention was low, with only 18% of the MSM reporting such activities.
Source: Finlayson TJ, et al. HIV risk, prevention, and testing behaviors among men who have sex with men—national HIV behavioral surveillance system, 21 U.S. cities, United States, 2008. MMWR 2011;60:1–13.
AIDS Funding Cuts
Despite announcing cutbacks in grant funding, and no new grants or funding until 2014, the Global Fund to Fight AIDS, TB, and Malaria (Geneva, Switzerland), a major financial supporter of the fight against these diseases, offered assurances that it is “alive and well” and that “rumors of [its] demise are greatly exaggerated.” Stating that the Global Fund Board decided at its last meeting to “transition to a new, more strategic approach to grant making that will begin in 2014,” the group said that it will disburse about US$10 billion during the remainder of its current (2011–2013) funding period, representing US$2 billion more than what it disbursed during 2008–2010. Citing the economic crisis in Europe as the major factor contributing to its monetary shortfall and recent funding and reorganization decisions, the group states, “The Global Fund has set as a goal to help save 10 million lives between today and 2016. The postponement of new funding is a setback to that goal,” but it believes “this goal is still achievable.”
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CD4 Cell Counts More Cost Effective Than Viral Load Testing
A study of the cost effectiveness of various monitoring strategies for antiretroviral therapy (ART) in Uganda, Africa, found that clinical monitoring plus routine measurements of CD4 cell counts was more cost effective than this approach plus routine viral load monitoring. The study authors concluded that both CD4 monitoring and starting a patient on ART were economically preferable to monitoring viral load. They evaluated three monitoring strategies in this randomized trial conducted as part of a home-based ART program: clinical monitoring with quarterly CD4 cell counts and viral load measurements; clinical monitoring and quarterly CD4 counts; and clinical monitoring alone. The intention-to-treat results per 100 individuals starting ART indicated that clinical monitoring/CD4 testing compared to clinical monitoring alone increased costs by US$20,458 and averted 117.3 disability adjusted life years (DALYs), while clinical monitoring/CD4/viral load testing compared to clinical monitoring/CD4 testing added US$142,458 and averted 27.5 DALYs.
Source: Kahn J, et al. CD4 cell count and viral load monitoring in patients undergoing antiretroviral therapy in Uganda: cost effectiveness study. Br Med J 2011;343:d6884.
New HIV Diagnostic Algorithm
Researchers from the National Center for HIV/AIDS, Hepatitis, STD, and TB Prevention (Atlanta, GA) evaluated an alternative HIV diagnostic algorithm that offers more rapid results to improve early detection of HIV-1 during the acute stages of infection and can accurately detect established HIV-1 infections. The alternative algorithm uses a next-generation immunoassay followed by an HIV-1/HIV-2 discriminatory supplemental test on the initial immunoassay-positive sample. Positive results on both tests are indicative of an HIV-positive diagnosis, whereas discordant test results necessitate nucleic acid amplification testing to detect viral nucleic acid sequences. The study authors reported that, among seroconverters, this alternative algorithm detected significantly more (103–134) infections than the current diagnostic algorithm (56), comprised of an immunoassay and supplemental testing with Western blot or immunofluorescence assay. The use of a fourth-generation immunoassay versus a third-generation assay for screening yielded a significantly higher detection rate of acute infections. In established HIV-1 infections, the current and alternative diagnostic algorithms performed equally well.
Source: Masciotra S, et al. Evaluation of an alternative HIV diagnostic algorithm using specimens from seroconversion panels and persons with established HIV infections. J Clin Virol 2011;52(suppl 1):S17-S22.
STDs
STD Trends in the U.S.
The U.S. Centers for Disease Control and Prevention (CDC) released 2010 national surveillance data on the three reportable diseases for which there are federally funded control programs: chlamydia, gonorrhea, and syphilis. Key findings for 2010 include an overall decrease in the rate of primary and secondary syphilis for the first time in 10 years—a 21% rate decrease among women, but a 1.3% increase in men. Although the rate of primary and secondary syphilis in the U.S. decreased 89.7% during 1990–2000, it then followed an upward trend each year from 2001 through 2009, finally changing trajectory in 2010. Indicative of lessening racial disparities, the rate of syphilis in blacks was 8 times the rate among whites in 2010, compared to 24 times higher among blacks in 1999. During the 4-year period 2006–2010, the CDC reported a 75% increase in syphilis rates among black men aged 15–19 years and a 134% increase among black men 20–24 years of age. Similarly for black women, the rate increased 46% for ages 15–19 years and 59% for women aged 20–24 years.
The data were less encouraging for gonorrhea and for sexually transmitted Chlamydia trachomatis. After a 10-year plateau in gonorrhea rates from 1996 to 2006, they decreased through 2009, reaching a new low in the history of national reporting. The overall rate then increased 2.8% in 2009–2010, and increased slightly again in 2010. The gonorrhea rate among women in the U.S. was 106.5 cases/100,000 population—highest among the age group 15–24 years—and 94.1/100,000 in men, with the largest number of cases among men aged 20–24 years. The number of cases of chlamydia infection reported to the CDC in 2010, more than 1.3 million, was the largest number of cases of any condition ever reported. The chlamydia infection rate of 426.0/100,000 population for 2010 is 5.1% higher than the rate for 2009. The CDC attributes the continuing rise in chlamydia case reports to an ongoing increase in screening for chlamydia infection, greater use of more sensitive tests, and more complete national reporting, but states that “it also may reflect a true increase in morbidity.”
Source: Centers for Disease Control and Prevention. “Sexually Transmitted Disease Surveillance, 2010.”
HIV and Syphilis Diagnoses Increase Among Young Black MSM
A similar trend was observed across 73 metropolitan areas of varying population sizes, comparing data from 2004–2005 with 2007–2008: diagnoses of HIV and primary and secondary syphilis infection increased among young men who have sex with men (MSM), and especially young black MSM. A comparison of diagnoses between those two time ranges revealed an increase in HIV diagnoses among young (13–24 years) black MSM in 85% of the metropolitan areas surveyed and an increase in syphilis diagnoses among young black MSM in 70% of areas. Overall, across all areas, the study found a 68.7% average increase in HIV diagnoses among young black MSM and a 203.5% average increase in primary and secondary syphilis in this same sector of the population. Regardless of the size of the metropolitan area, the youngest group of black men had the highest average percentage increase in diagnoses of HIV and syphilis.
Source: Torrone EA, et al. Increased HIV and primary and secondary syphilis diagnoses among young men—United States, 2004–2008. J Acq Immune Def Syn 2011;58(3):328–335.