Abstract
HIV
More Evidence to Support Early ART
T
This finding has particularly important implications for Africa, as 54% of the study participants were from Africa and 82% of the cases of HIV transmission were observed there. The study also found a relative reduction of 41% in the number of HIV-1–related clinical events.
Source: Cohen MS, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med July 18, 2011; doi: 10.1056/NEJMoal1105243
ART and Life Expectancy in Uganda
HIV-infected persons in Uganda who receive combination antiretroviral therapy (cART) can expect nearly normal life expectancy, with substantial variation in the projected number of additional years to live depending on gender and baseline CD4 count. This finding is based on a study of more than 22,000 patients that initiated ART during the study period. “The substantial life expectancy afforded by widespread access to cART underscores the fact that HIV diagnosis in resource-limited setting is no longer a death sentence,” conclude the authors.
For the entire study cohort, life expectancy at 20 years of age was 26.7 additional years of life, and at age 35 was 27.9 years of additional life. For men, these figures were substantially lower: 19/1 years at age 20 and 22 years at age 35; compared to 30.6 years at age 20 and 32.5 years at age 35 for women. The authors attribute this difference largely to treatment differences, with men typically accessing care at a later stage of disease and having a higher likelihood of loss to follow-up.
Overall, as baseline CD4 counts increased, life expectancy also rose. A CD4 count of less than 50 cells/mm3 was associated with life expectancy of 13.5 and 14.2 years at ages 20 and 35 years, respectively. Whereas, persons with a CD4 count of 250 cells/mm3 or higher at initiation of ART had a life expectancy of 37.4 and 35.1 years at ages 20 and 35, respectively.
Source: Mills EJ, et al. Life Expectancy of persons receiving combination antiretroviral therapy in low-income countries: A cohort analysis from Uganda 2011. Ann Intern Med 2011;155:209–216.
Lactobacillus-Based Microbicide Gel Lowers SHIV Transmission Risk in Monkeys
Lacctobacilli are bacterial components of the biofilm that coats and protects themucosal surfaces of the female reproductive tract. An engineered version of Lactobacillus jensenii that expresses an HIV-1 entry inhibitor was formulated into a gel. The live engineered L. jensenii was delivered to the macaques in hydroxyethylcellulose via vaginal inoculation on 5 successive days to achieve sustained colonization and secretion of the entry inhibitor protein. The animals then received repeated vaginal challenges with chimeric simian HIV (SHIV). Compared to control animals, the treated macaques had a statistically significant 63% reduction in SHIV transmission. In an unexpected finding, when breakthrough infection occurred in the treated macaques, peak viral loads were sixfold lower than in infected control animals.
The HIV-1 entry inhibitor used in this experiment was the cyanovirin-N (CV-N) protein. The modular nature of the Lactobacillus expression system allows for the use of other HIV inhibitory proteins such as CCR% or C1C5 RANTES, or of multiple protein inhibitors. The study authors reported no evidence of inflammation induced by the Lactobacillus jensenii gel.
Source: Lagenaur LA, et al. Prevention of vaginal SHIV transmission in macaques by a live recombinant Lactobacillus” Mucosal Immunol July 6, 2011; doi:10.1038/mi.2011.30
More Frequent HIV Testing Recommended for MSM
It might be a good idea for sexually active men who have sex with men (MSM) to undergo HIV testing more often than once a year, and perhaps every 3–6 months, based on an analysis of Nation HIV Behavioral Surveillance System (NHBS) data by the Centers for Disease Control and Prevention (CDC). MSM account for about 2% of the U.S. population 13 years of age or older, but they comprise a disproportionate 59% of persons diagnosed with HIV infection, according to statistics from 2009.
The review of NHBS data from 2008 revealed that of the more than 7,000 MSM interviewed and tested for HIV as part of the study—none of whom had a previous positive HIV test—7% of the MSM who reported having been tested during the past 12 months had a positive HIV test result. Among all the MSM who participated in the study, 680, or 9%, were HIV infected. Within this group, 16% had never been tested for HIV, and 29% had been tested during the previous 6 months.
Source: MMWR 2011;60:694–699.
Racial Disparities in HIV Infection Among MSM
To understand the factors associated with disparities in HIV infection between black and white MSM in the United States, researchers reviewed the survey data and HIV test results for MSM who took part in the 2008 National HIV Behavioral Surveillance System (NHBS). Among more than 5000 MSM not previously diagnosed with HIV infection, the two factors with a statistically significant association were having “HIV-infected partners” or having “partners of unknown status.” Only “partners of unknown status” was more common among black compared to white MSM. Among MSM who had a previous diagnosis of HIV positivity, black MSM were less likely to be receiving ART. The authors of this study concluded the following: “Efforts to encourage discussions about HIV status between MSM and their partners and decrease barriers to ART provision among black MSM may decrease transmission.”
Source: Oster A, et al. Understanding disparities in HIV infection between black and white MSM in the United States. AIDS 2011;25:1103–1112.
Development of a New HIV Coreceptor Inhibitor
Cenicriviroc (CVC) is the second in a class of CCR5 HIV coreceptor inhibitors, along with maraviroc, and it has shown potent antiretroviral activity in patients with HIV-1. A phase 1 single-dose, randomized crossover study trial in healthy volunteers, designed to evaluate the pharmacokinetics, safety, and tolerability of CVC and tenofovir (TDF) coadministration, found the combination regimen to be safe and well-tolerated, with fewer adverse events reported than when either drug is given alone. Results of the trial were presented at the 6th International AIDS Society conference in Rome, Italy. Study subjects received a single dose of CVC (150 mg), TDF (300 mg), or combination of the two, with a 14-day washout period between regimens. The results led to several conclusions: coadministration introduced no safety issues; it did not affect the pharmacokinetics of CVC; and it did not affect the bioavailability or clearance (AUC) of TDF, but the maximum plasma concentration (Cmax) of TDS was about 36% higher, suggesting that CVC may affect the rate of absorption of TDF. Additionally, the findings indicated no need to adjust the doses when coadministering the two drugs.
Source:
ART Accelerates Mitochondrial Aging
One factor that may be contributing to the premature aging reported among HIV-infected individuals successfully treated with antiviral therapy is accelerated mitochondrial damage caused by the accumulation of mutations in somatic mitochondrial DNA (mtDNA). These are the same types of mutations seen in mtDNA in association with normal aging, but they are appearing at a younger age in HIV patients treated with nucleoside analog antiretroviral drugs. The results of molecular analysis of the DNA sequences suggest that there is not a higher level of mutagenesis in the mtDNA of treated HIV patients, but rather more rapid turnover of mtDNA resulting in the accelerated expansion of age-related somatic mutations that already existed.
Source: Payne B, et al. Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations. Nat Genet 2011;43:806–810.
Southern States are Home to HIV/AIDS–Poverty Combination
Among 43 states in the United States, the vast majority of counties that have high rates of both HIV infection and poverty are located in the South. USA Today reporters analyzed HIV infection rate data stratified by county that was collected as part of Emory University's AIDSVu project. Whereas HIV infection tended to cluster in big cities on the East Coast and West Coast in the early years of the AIDS epidemic, a geographic shift has resulted in a disproportionate number of cases among African American men and women living in poverty in 11 southern states. The reporters found that 169 of 175 counties ranked among the top 20% for both HIV and poverty are located in the South. Among the factors that may contribute to this link are access to sex education and education in general, the age when teens/children first become sexually active, drug use, and family structure/parental supervision.
Source: Sternberg S and Gillum J. USA Today July 11, 2011
Hepatitis C Virus
Sexual Transmission of HCV Among HIV-infected MSM
The risk for sexual transmission of hepatitis C virus (HCV) has not been well studied. The main risk of HCV transmission is through exposure to infected blood, with intravenous drug abusers being the population at greatest risk for HCV infection. Overall, approximately 3.2 million people in the United States are infected with HCV.
As reports of sexual transmission among HIV-infected men who have sex with men (MSM) have appeared in the literature, researchers at Mount Sinai Medical Center, in New York City, set out to conduct a formal, matched case-control study. They evaluated 74 HIV-infected MSM with recently acquired HCV infection and no reported history of injection drug use between 2005–2010. They concluded that high-risk sexual behavior (including anal intercourse with no condom and ejaculation, group sex, and sex while high on drugs, and especially methamphetamine use) was the most likely mode of transmission. Analysis of HCV derived from the infected men identified five clusters of closely related HCV variants.
Source: MMWR 2011;60:945–950.
Sexually Transmitted Diseases
Ceftriaxone Resistance in New
Neisseria gonorrhoeae
Strain
Researchers in Japan have described a strain of Neisseria gonorrhoeae (H041) that is highly resistant to the extended-spectrum cephalosporin ceftriaxone and for which there may be no effective antibiotic treatment. They present a variety of test results to characterize H041 genetically and phenotypically and to confirm that it is in fact a new strain. According to the authors, H041 demonstrated resistance to ceftriaxone fourfold to eightfold higher than previously identified resistant isolates. They attribute the resistance to four newly identified amino acid changes in the penA mosaic gene of N. gonorrhoeae
Source: Ohnishi M, et al. Sex Transm Infect 2011;87:A76.
Rates of Human Papillomavirus-Positive Throat Cancer Rising in Men
“Should recent incidence trends continue, the annual number of HPV-positive oropharyngeal cancers among men is expected to surpass that of cervical cancers among women by the year 2020 in the U.S.,” stated a group of researchers who presented their most recent findings at the annual meeting of the American Society of Clinical Oncology. The study documented a 225% increase in the incidence of HPV-positive oropharyngeal cancer from 1988–2004, and a 50% decline in HPV-negative throat cancer. The researchers used genetic testing methods to determine the HPV status and viral load of oropharyngeal tumors in 271 cases during the study period. They found that HPV prevalence increased over time. One of the detection methods used, for example, identified a big jump in HPV prevalence from more than 16% for the time period 1984–1989 to 72.7% during 2000–2004.
Source: Chaturvedi A, et al. Human papillomavirus (HPV) and rising oropharyngeal cancer incidence and survival in the United States.
HPV Vaccination Having a Positive Impact
A study of trends in histopathologic cervical abnormalities among young women before and after the availability of an HPV vaccine in Australia revealed a 0.38% decrease in the incidence of high-grade abnormalities among girls younger than 18 years after nationwide implementation of the vaccine between 2007–2009. This decrease was progressive and differed significantly from the trend in incidence reported before the vaccine became available. No similar trend was reported for low-grade cervical abnormalities.
Source: Brotherton J, et al. Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: An ecological study. Lancet 2011;377:2085–2092.