Abstract
HIV
New Study Data Guide HAART Initiation Decision-Making
An observational cohort study of nearly 9,500 HIV-infected patients with CD4 cell counts less than 800 per microliter estimated the clinical benefit of initiation or deferral of highly active antiretroviral therapy (HAART) on a month-to-month basis, covering more than 52,000 person-years of follow-up. All patients were AIDS-free and HAART-naïve. They were participants in the Concerted Action on Seroconversion to AIDS and Death in Europe (CASCADE) collaborative trial. The primary outcome of the current study was time to AIDS or death among those who initiated HAART in a given month compared to those who deferred HAART. The researchers pooled the monthly subcohorts of patients and stratified the samples by CD4 cell count.
For the CD4 cell count strata of 200–349 and 350–499, the reduction in risk of AIDS or death with earlier initiation of HAART was 41% and 25%, reaching significance only for the 200–349 cohort. Patients with CD4 cell counts 500–799 per microliter had no clinical benefit from early initiation of HAART. Risk reduction of all-cause mortality associated with HAART initiation was 29% in the 200–349 cohort and 49% in the 350–499 cohort, significant only in the higher CD4 cell count group, and no benefit was achieved in the 500–799 cohort.
The authors conclude that progression to AIDS was slowed among patients with CD4 cell counts less than 500 per microliter when HAART was started rather than deferred in a given month. In an accompanying commentary, Daniel Kuritzkes, M.D. (Brigham and Women's Hospital and Harvard Medical School, Boston, MA), cites the large number of patients studied and the extensive follow-up as strengths of the study. He also points out some potential limitations of the study design and concludes that the results are in agreement with other cohort studies regarding the benefits of starting HAART early in patients with CD4 cell counts below 500 per microliter. However, Kuritzkes notes, “While awaiting more definitive data, the pros and cons of starting HAART at CD4 cell counts above 500 per microliter should be weighed carefully by clinicians and patients.”
Source: Writing Committee for the CASCADE Collaboration. Timing of HAART initiation and clinical outcomes in human immunodeficiency virus type 1 serconverters. Arch Intern Med 2011;171:1560–1569 and Kuritzkes DR. HAART for HIV-1 infection: Zeroing in on when to start. Arch Intern Med 2011;171:1569–1570.
Efavirenz Shown to Be Safe in First Trimester of Pregnancy
An updated meta-analysis of the frequency of birth defects among infants exposed to efavirenz during the first trimester of pregnancy supports earlier findings that there is no significant increase in birth defects among infants exposed to efavirenz-containing versus non-efavirenz-containing antiretroviral regimens. The current study expands the database to include 21 studies and live births to 1437 women who received efavirenz during the first trimester. The relative risk (0.85) of birth defects among women on an efavirenz-based regimen compared to those on a non-efavirenz-based regimen was not significant, and only one neural tube defect was observed, for an incidence of 0.07%.
Source: Ford N, et al. Safety of efavirenz in first-trimester of pregnancy: An updated systematic review and meta-analysis. AIDS 2011;25:doi: 10.1097/QAD.0b013e32834cdb71.
Abacavir Not Associated with Increased Risk of Cardiovascular Disease
In contrast to evidence from some cohort studies suggesting that abacavir use is associated with an increased risk of cardiovascular disease, a meta-analysis of 28 randomized controlled trials encompassing more than 9,000 subjects that compared abacavir-containing ART regimens to regimens without abacavir found no significant increase in the occurrence of myocardial infarction (risk ratio 0.73), major cardiovascular events (risk ratio 0.95), overall mortality (risk ratio 1.20), or adverse events requiring discontinuation of treatment (risk ratio 0.82).
Source: Cruciani M, et al. Abacavir Use and Cardiovascular Disease Events: A Meta-Analysis of Published and Unpublished Data. AIDS 2011;25:1993–2004.
Quad Regimen Achieves Primary Endpoint in Phase 3 Trial
The single-tablet, once-daily “Quad” regimen achieved the primary endpoint of a second phase 3 clinical trial, defined as viral load less than 50 copies per milliliter after 48 weeks in HIV-1–infected, treatment-naïve patients. Gilead Sciences reported that its investigational combination regimen, which includes elvitegravir (150 mg), cobicistat (150 mg), emtricitabine (200 mg), and tenofovir (300 mg), was successful in reducing HIV RNA levels to target levels in 90% of patients, compared to 87% of patients who received ritonavir (100 mg)-boosted atazanavir (300 mg) plus emtricitabine/tenofovir (Truvada). Gilead plans to file for regulatory approval in the U.S. by the end of 2011. Discontinuation of treatment due to adverse events was greater among the ritonavir-boosted atazanavir group compared to the Quad group (5.1% vs 3.1) due primarily to the occurrence of elevated bilirubin levels.
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Hormonal Contraception Linked to Increased HIV Transmission Risk
In sub-Saharan Africa, 60% of HIV infections occur in women, and a large proportion of women in this region use hormonal contraception. Evidence to support an association between hormonal contraceptive use and an increased risk of HIV transmission from women to men or men to women comes from a prospective study of nearly 3800 heterosexual HIV-1–serodiscordant couples in seven African countries. Most of the women in the study used long-acting injectable contraception. Compared to women who did not use contraception, these women were two times more likely to acquire HIV from their male partners, and their partners also had a twofold increased risk of acquiring HIV infection. Although oral contraceptive use was also associated with an increased HIV transmission risk compared to non-use of contraception—both from women to men and from men to women—the number of oral contraceptive users in the study was too low for the results to achieve statistical significance.
Overall, the HIV transmission rate from the male partner to the seronegative female partner was 6.61 per 100 person-years with hormonal contraception and 3.78 per 100 person-years in the absence of hormonal contraception. When the HIV-seronegative partner was the man, HIV transmission rates to the female partner were 2.61 per 100 person-years when the women used a hormonal contraceptive and 1.51 per 100 person-years when she did not. The authors of the study recommend counseling for women using hormonal contraception on the increased risk of HIV transmission and the importance of condom use as a protective measure.
Source: Heffron R, et al. Use of hormonal contraceptives and risk of HIV-1 transmission: A prospective cohort study. Lancet Infect Dis October 4, 2011; doi: 10.1016/S1473-3099(11)70247-X and Morrison CS. Commentary: Hormonal contraception and HIV: An unanswered question. Lancet Infect Dis October 4, 2011; doi:10.1016/S1473-3099(11)70254-7.
Small Microfluidic Device Tests Blood for HIV and Syphilis
The mChip (mobile microfluidic chip forms the core of a handheld point-of-care device capable of testing simultaneously for HIV and syphilis infection in a drop of blood. Professor Samuel Sia's laboratory at the Fu Foundation School of Engineering, Columbia University, designed the disposable, credit-card–sized chip using microfluidic and nanoparticle technology. The lab-on-a-chip device can perform all the steps of an enzyme-linked immunosorbent assay (ELISA) assay using 1 microliter of unprocessed whole blood, such as a sample obtained from a finger-prick. To ensure that the device is suitable for use in remote settings, the researchers made it easy to use, with quantitative results available in less than 15 minutes and requiring no interpretation of the signal. Each disposable chip costs about $1.00 and the accompanying instrument about $100.
In a Technical Report in Nature Medicine, Chin and co-workers from Professor Sia's laboratory report on the use of the mChip assay to test hundreds of human blood samples collected in Rwanda. They found that the device was able to diagnose HIV and syphilis simultaneously with sensitivities and specificities comparable to those achieved with reference benchtop assays. The assay results will be linked to a central health records database with the goal of achieving early detection and treatment of these infections in pregnant women, thereby preventing stillbirths and minimizing possible adverse health consequences for infected mothers and children.
Source: Chin CD. Microfluidics-based diagnostics of infectious diseases in the development world. Nature Med 2011;17:1015–1019.
New AIDS Cases Decrease Thirty-Five Percent in New York City
New data on AIDS diagnosis rates released in the Mayor's Management Report for New York City document 2225 newly diagnosed adults with AIDS in fiscal year 2011, compared to 2969 new cases diagnosed in 2010 (a 25% reduction) and 4164 cases recorded in 2003. Dr. Monica Sweeney, assistant commissioner of the Bureau of HIV. Prevention and Control in NYC's Department of Health and Mental Hygiene, told The New York Times that while the number of new cases of HIV infection has also been trending downward, the substantial drop in AIDS diagnoses is mainly attributable to better treatments and improved patient adherence. In New York City, new HIV infection is most common among men less than 30 years of age, and especially black and Latino men and men who have sex with men (MSM), as well as among black women. Mother-to-child HIV transmission is now rare and new infections caused by injection drug use have dropped substantially, according to Sweeney.
Source: The New York Times, September 16, 2011.
Human Papillomavirus INFECTION
Link Between Rising Rate of Oropharyngeal Cancer and HPV Infection
A study has linked the increasing incidence of oropharyngeal cancers with prolonged survival in the United States with the rise in human papillomavirus (HPV) infection. HPV status was determined for 271 oropharyngeal cancer samples collected over a 20-year period (1984–2004) using analytical methods to quantify HPV16 viral load and mRNA expression. Over time, HPV prevalence increased significantly. For example, genotyping revealed a rise in HPV in the cancer samples from 16.3% during the timeframe 1984–1989 to 71% for 2000–2004. Overall, the population-level incidence of HPV-positive oropharyngeal cancers rose by 225% from 1988–2004. During the same time period, the incidence of HPV-negative cancers decreased by 50%.
Patients with HPV-positive oropharyngeal squamous cell carcinomas tend to survive substantially longer than those with HPV-negative lesions. The association between HPV infection and longer survival held true in this study population, as median survival for HPV-positive patients (131 months) was significantly longer than for HPV-negative patients (20 months).
Source: Chaturvedi AK, et al. Human papilloma virus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011;doi:10.1200/JCO.2011.36.4596.
HPV Triaging Reduces Colposcopy Referrals
A previous study of samples obtained during routine cervical screening in the U.K. showed that HPV testing of abnormal samples—demonstrating either borderline cytology or mild dyskaryosis—was feasible, acceptable to women, and cost-effective. A recent study evaluated the likely effects of HPV triaging on rates of referral to colposcopy and the positive predictive value of HPV testing. The results indicate that HPV triaging of abnormal cervical screening samples would eliminate the need for colposcopy in about a third of the (HPV-negative) women, who would be returned immediately to routine recall. Among the HPV-positive women referred for colposcopy, a substantial proportion would not require repeat cytology due to the positive findings on HPV testing.
The study data yielded a 16.3% positive predictive value of an HPV test for cervical intraepithelial neoplasia (CIN)2 or worse, and 6.1% for CIN3 or worse. The authors report HPV-positive rates of 53.7% among samples with borderline cytology and 83.9% for those demonstrating mild dyskaryosis. They note that the rate of HPV-positive results varied considerably between testing sites due mainly to the different thresholds used by individual laboratories to determine abnormal test results.
Source: Kelly RS, et al. HPV testing as a triage for borderline or mild dyskaryosis on cervical cytology: Results from the sentinel sites study. Br J Cancer 2011;105:983–988.