Abstract
HIV
Scope of HIV Infection on the 30th Anniversary of AIDS
The Centers for Disease Control and Prevention (CDC) released an HIV Surveillance report marking the 30th anniversary (1981–2011) anniversary of AIDS. The introduction of highly active antiretroviral therapy contributed to a substantial decline in AIDS diagnoses and deaths from 1995–1998, and those numbers remained essentially stable from 1999–2008, with an average of more than 38,000 AIDS diagnoses and nearly 17,500 deaths per year. AIDS still casts a large shadow, as an estimated 1.2 million people were living with HIV in the United States at the end of 2008, including about 20% with undiagnosed infections.
The surveillance data for 2008 reveal that three quarters of the persons living with HIV in the United States were male, and nearly two thirds of those males were men who have sex with men (MSM). HIV prevalence among African Americans/blacks was about 8 times the rate for whites; Hispanics/Latinos had a 2.5 times greater prevalence of HIV than whites. Undiagnosed HIV infection was most common among persons 13–24 years of age and 25–34 years of age than among older age groups, and was estimated at 25% among males with high-risk heterosexual contact, and 22.1% among MSM.
The editors of the surveillance report published in MMWR. Morbidity and Mortality Weekly Report note that “late diagnosis of HIV infection is common,” with 33% of persons with newly diagnosed HIV in 2008 developing AIDS within 1 year of diagnosis.
Source: MMWR Morb Mortal Wkly Rep 2011;60:689–693.
Abacavir and Tenofovir Both Linked to (Different) Cardiovascular Disease Risk
A link between abacavir use in HIV therapy and cardiovascular disease risk is not news, but Choi and colleagues questioned whether this link may be due at least in part to the preferential use of abacavir over tenofovir in patients with kidney disease. Based on results of their study designed to evaluate cardiovascular disease risk associated with abacavir compared to tenofovir, they report that recent exposure to either drug was associated with an increased risk of cardiovascular disease: abacavir exposure was linked to a significant increase in the cardiovascular event rate (defined as coronary, cerebrovascular, or peripheral arterial disease), but tenofovir was not; and tenofovir was associated with a significant increase in the risk of heart failure, while abacavir was not.
The authors studied nearly 11,000 HIV-infected American veterans over a 10-year time period, categorizing the patients based on exposure or nonexposure to one of the two drugs within the previous 6 months. The outcomes were defined as time to first atherosclerotic cardiovascular event and time to heart failure. The researchers calculated age-standardized event rates and used multivariate-adjusted models, including measurements of kidney function to determine hazard ratios between drug exposure and outcomes.
Source: AIDS 2011;25:1289–1298.
No Link between HIV Infection and Vitamin D Deficiency
A study of vitamin D deficiency in HIV-positive versus HIV-negative women found no significant association between HIV infection and vitamin D deficiency. The study population was comprised of 1800 middle-aged, ethnically diverse women enrolled in the Women's Interagency HIV Study (WIHS). The majority (63%) of the women tested had low blood levels (<20 ng/mL) of vitamin D. This cohort included 60% of the HIV-positive women and 72% of the HIV-negative women. African American women had the highest rates of vitamin D deficiency. Other predictive factors included Hispanic ethnicity and body mass index.
Source: Adeyemi O, et al. J Acquir Defic Syndrome 2011;57:197–204.
Vitamin D Deficiency Associated with Greater Risk of Mortality, HIV Disease Progression, and AIDS-Related Events
Among nearly 2000 randomly selected HIV-positive individuals participating in the EuroSIDA study, those with higher levels of vitamin D (≥12 ng/mL) had a significantly lower risk of HIV-related clinical disease progression and a significantly lower incidence of all-cause mortality and AIDS-related events than individuals with low vitamin D levels (<12 ng/mL). Risk factors associated with low levels of vitamin D included older age, black ethnic origin, sampling during winter, and HIV infection through nonhomosexual exposure. Use of protease inhibitors was associated with higher vitamin D levels. Among the HIV-infected study participants found to have vitamin D deficiency, 83% were on combined antiretroviral therapy.
Source: Viard J-P, et al. AIDS 2011;25:1305–1315.
Early Initiation of Antiretroviral Therapy Offers Minimal Benefit
Early initiation of combination antiretroviral therapy (beginning when CD4 counts exceed 500 cells per microliter) was associated with a minimal reduction in risk of AIDS incidence and/or death compared to initiation of combination antiretroviral therapy (cART) when the baseline CD4 count is 351–500 cells per microliter, according to the results of a study of 432 HIV-infected adults enrolled in the Australian HIV Observational Database (AHOD). All of the patients in the study had baseline CD4 counts greater than 350 cells per microliter at the start of cART, and the mean CD4 counts for all three patient groups (stratified into baseline cell counts of 351–500, 501–650, and>650 cells per microliter) exceeded 500 cells per microliter by 12 months of cART. After 72 months of treatment, mean CD4 counts for all groups exceeded 688 cells per microliter. Compared to patients starting from a baseline of 351–500 CD4 cells per microliter, those in the two higher baseline strata on initiation of cART benefitted from only a minimal reduction in risk of AIDS incidence and/or death (an 8% reduction and an absolute risk reduction of 0.33 per 1000 treated patient-years).
Source: Wright S, et al. J Acquir Defic Syndrome (published online ahead of print) DOI: 10.1097/QAI.0b013e318225ba62
Sex Disparities in ART Outcomes in a Resource-Limited Setting
Among nearly 13,000 HIV-infected persons receiving antiretroviral medication and care through a program in urban Tanzania, clinical and immunologic outcomes differed significantly between men and women. The study, conducted over a period of more than 3.5 years, evaluated sex differences associated with three variables: mortality, immunologic failure (defined as a CD4 count<100 cells per microliter after at least 6 months of ART), and loss to follow-up. After adjusting for other risk factors, multivariate analyses showed that men had a significantly higher risk for all three variables compared to women. As a group, the men were significantly more immunocompromised at enrollment into the study (based on disease stage and mean CD4 cell counts). The authors concluded, however, that advanced immunodeficiency at enrollment and nonadherence to care accounted for only 17% of the inferior mortality reported among the male cohort.
Source: Hawkins C, et al. AIDS 2011;25:1189–1197.
Rate of Non-AIDS–Defining Cancers Increasing
Even as HIV-infected persons on HAART are living longer healthier lives, data on cancer prevalence indicate that people with HIV face a higher rate of cancers not previously associated with HIV infection or AIDS, including lung, head and neck, liver, kidney, and anal cancers. This trend is drawing attention to questions about how best to treat cancer in people taking highly active antiretroviral therapy (HAART). John Deeken, M.D., Georgetown Lombardi Comprehensive Cancer Center, is national chairman of the first study to come out of the AIDS Malignancy Consortium, a National Cancer Institute-supported clinical trials group. Dr. Deeken presented early study results at the recent American Society of Clinical Oncology (ASCO) annual meeting in Chicago. As people with HIV are typically not included in clinical trials for cancer treatments, there are few data available to guide cancer therapy in HIV-infected individuals on HAART. The risk of further immunosuppression, drug–drug interactions, and serious adverse effects is of particular concern in this population.
Deeken reported on the first chemotherapeutic drug studied, sunitinib, an oral medication approved for the treatment of kidney cancer that inhibits enzymes required for tumor new blood vessel formation and cell growth. Agents used in HAART may affect some of the same enzymes involved in sunitinib metabolism. The results indicated no safety issues related to sunitinib use by patients taking non-ritonavir–based HAART regimens, whereas patients taking a ritonavir-based therapy had more side effects, including higher rates of neutropenia.
Source: Georgetown University media statement:
Acceptability of PrEP for HIV Prevention
Among persons at increased risk for acquiring HIV in Lima, Peru—including female sex workers, male-to-female transgendered persons, and men who have sex with men—the acceptability of pre-exposure prophylaxis (PrEP) as an HIV prevention strategy ranged from 19.8 to 82.5 on a scale of 100 for 8 hypothetical PrEP scenarios. Among the factors evaluated, out-of-pocket cost, efficacy, and potential side effects were significantly associated with PrEP acceptability. Additional concerns included potential sexual risk disinhibition, stigma and discrimination linked to PrEP use, and mistrust of health care professionals.
Source: Galea JT, et al. Int J STD AIDS 2011;22:256–262.
Hepatitis C Virus
Telaprevir Improves Virologic Response to Peginterferon-Ribavirin in Treatment-Naïve Patients
An international, phase 3, randomized, double-blinded, placebo-controlled trial designed to assess the benefit of adding telaprevir, a protease inhibitor, to the standard treatment for HCV infection (peginterferon alfa-2a plus ribavirin), showed improved efficacy with telaprevir and the potential to shorten the duration of treatment in a majority of patients. The study comprised three treatment groups: the T12PR group, which received peginterferon-ribavirin (PR) combined with telaprevir for 12 weeks followed by PR along for 12 weeks if HCV RNA was undetectable at weeks 4 and 12, or for 36 weeks if HCV RNA was present; the T8PR group, which received telaprevir with PR for 8 weeks and PR plus placebo for 4 weeks, followed by 12 or 36 weeks of PR depending on HCV RNA detection; and the PR group, which received PR plus placebo for 12 weeks, followed by 36 weeks of PR. The primary end point was a sustained virologic response, defined as undetectable plasma HCV RNA 24 weeks after the last dose.
A sustained virologic response was reported in significantly greater numbers of patients in the T12PR or T8PR group than in the PR group—75% and 69%, respectively, compared to 44% for the PR group. More than half (58%) of the patients who received telaprevir required only 24 weeks of total treatment. Compared to PR along, combination treatment with telaprevir was associated with a higher rate of anemia, gastrointestinal side effects, and skin rashes.
Source: Jacobson IM, et al. N Engl J Med 2011;364:2405–2416.
Sexually Transmitted Diseases
Few Clinics Comply with CDC Guidelines for HSV Testing
The Centers for Disease Control and Prevention recommends that clinics caring for patients at risk for sexually transmitted diseases (STDs) provide both virologic and serologic testing for the herpes simplex virus type 1 (HSV-1) and HSV-2. However, a telephone survey of the 230 largest STD clinics in the United States found that only 23% (50) had both serologic and virologic testing available. Eighty-seven (37%) clinics offered neither serologic nor virologic testing for HSV, while 36% (87) had only virologic testing capability and 4% (8) offered only serologic testing.
The estimated prevalence of HSV in the United States is 57.7% for HSV-1 and 17.0% for HSV-2. The survey results indicated that HSV testing of any type was significantly more likely to be available in the western and northern regions of the United States compared to the southern and midwestern regions. The authors reported wide variation from clinic to clinic in the ability to diagnose HSV and the techniques used.
Source: Warren T, et al. Sex Transm Dis 2011;38:267–269.