Abstract
HIV
Positive Results for HCV/HIV Combination Regimens
Good news for patients coinfected with genotype 1 hepatitis C virus (HCV) and HIV was presented at the recent 19th Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, Washington. Interim results from an ongoing phase 2 study of the antiviral drug telaprevir (Incivek®, Vertex Pharmaceuticals, Cambridge, MA), given in combination with pegylated-interferon and ribavirin in people coinfected showed that 74% (28/38) of patients had undetectable HCV RNA 12 weeks after treatment ended, compared to 45% (10/22) of patients treated with pegylated-interferon and ribavirin alone. Vertex, which is enrolling coinfected patients in a phase 3 study, reported that telaprevir was well tolerated with Atripla®-based (Bristol-Myers Squibb, New York, NY and Reyataz®-based (Bristol-Myers Squibb) HIV treatment regimens, with similar CD4 counts between the two groups and no evidence of HIV viral load breakthrough in either group. Merck presented 12-week posttreatment interim analysis of phase 2b clinical study evaluating bociprevir (Victrelis®, Merck Sharp & Dohme Corp., Whitehouse Station, NJ) in combination with pegylated-interferon and ribavirin and reported that a higher percentage of patients receiving bociprevir (60.7% versus 26.5%) had undetectable HCV RNA.
Source: Vertex Pharmaceuticals (
Quad Regimen Has Fewer Side Effects
Also reported at the CROI 2012 conference, by Gilead Sciences, were results from a 48-week phase 3 trial in treatment-naïve HIV-infected adults comparing the company's four-drug Quad antiretroviral drug regimen to Atripla. In addition to demonstrating efficacy that was not inferior to Atripla, the Quad regimen had a comparable safety profile and was better tolerated with regard to neurological side effects, lipid levels, and rash.
Source: Gilead Sciences (
Tenofovir Use Linked to Kidney Disease Risk
A study of nearly 11,000 HIV-infected patients who initiated antiretroviral therapy over a 10-year period from 1997–2007 found tenofovir exposure to be a significant, independent, and irreversible risk factor for kidney disease. For each year of exposure to tenofovir, risk of proteinuria increased 34%, risk of rapid decline in kidney function rose 11%, and risk of chronic kidney disease increased 33%. “Because subtle kidney function decline affects long-term morbidity and mortality, the balance between efficacy and probable adverse effects requires further study,” concluded the authors.
Source: Scherzer R, Estrella M, Li Y, et al. Association of tenofovir exposure with kidney disease risk in HIV infection. AIDS 2012;26:867–875.
Risk of Sexual HIV Transmission Despite Effective HAART
A resurgent HIV epidemic involving HIV-infected men who have sex with men (MSM) receiving highly active antiretroviral therapy (HAART) may be due to incomplete suppression of HIV in semen and genital shedding of virus as a result of localized inflammation. An evaluation of paired semen and blood samples in HIV-infected MSM on stable HAART showed that HIV-1 was detectable in 18% of blood samples and 30% of semen samples. Among 83 men in whom HIV was undetectable in plasma, 25% had evidence of HIV in semen with copy numbers ranging from 80 to 2560. Using multivariate analysis of clinical and behavioral data, the study authors found a significant association between seminal HIV detection and sexually transmitted infection/urethritis, tumor necrosis factor-α (TNF-α), and unprotected insertive anal sex with an HIV-infected partner. They concluded that sexually transmitted infections (STIs) and genital inflammation may be able to override the suppressive effects of HAART on seminal HIV shedding in MSM, creating a potential for increased transmission risk.
Source: Politch JA, Mayer KH, Welles SL, et al. Highly active antiretroviral therapy does not completely suppress HIV in semen of sexually active HIV-infected men who have sex with men. AIDS 2012;doi:10.1097/qad.0b013e328353b11b
Second-Line Monotherapy Promising in Resource-Limited Settings
At five sites in Africa and Asia that are part of the AIDS Clinical Trials Group (ACTG), HIV-infected patients with plasma HIV-1 RNA levels of 1000–200,000 copies per milliliter on first-line non-nucleoside reverse transcriptase inhibitor three-drug combination antiretroviral therapy (ART) were given lipinavir/ritonavir (LPV/r monotherapy as a second-line treatment. Nearly all of the individuals screening for the study had mutations associated with drug resistance. Of the 122 participants who remained on the LPV/r regimen for 24 weeks (87% of the total group), 62 subjects had HIV-1 RNA levels less than 400 at week 24 and 30 had levels of 40–200 copies per milliliter. Of the 15 subjects in whom virologic failure developed on monotherapy, 13 (and 1 subject without virologic failure) added emtricitabine and tenofovir. Of these 14 individuals, 11 achieved HIV-1 RNA levels less than 400 copies per milliliter at study week 48.
Source: Bartlett JA, Ribaudo HJ, Wallis CL, et al. Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings. AIDS 2012;doi:10.1097/QAD.0b013e328353b066
IRIS Increases Mortality Risk
Among HIV-infected individuals who initiated or resumed combination antiretroviral therapy (cART) in a recently reported study, immune reconstitution inflammatory syndrome (IRIS) development in more than 10%, substantially increasing their risk of mortality. Despite the overall efficacy of cART, with reported declines in HIV-RNA viral load and increased CD4 counts among the patient cohort studies, the risk for all-cause mortality approximately doubled for patients with a diagnosis of a type B- or C-defined IRIS (based on CDC disease definitions). IRIS was independently associated with a CD4 count less than 50 cells per microliter (versus ≥200 cells per microliter) and a viral load greater than 5.0 log10 copies (versus less than 4.0 log10 copies).
Source: Novak RM, Richardson JT, Buchacz K, et al. Immune reconstitution inflammatory syndrome: incidence and implications for mortality. AIDS 2012;26:721–730.
Pulmonary Hypertension Is Increasingly Common
Abnormal cardiopulmonary function, related to pulmonary hypertension and chronic obstructive pulmonary disease, evident on echocardiographic assessment is relatively common in HIV-infected individuals and may develop secondary to inflammation. Pulmonary hypertension measured on Doppler echocardiography was associated with respiratory symptoms, more advanced HIV disease, airway obstruction, abnormal diffusing capacity for carbon monoxide, and systemic and pulmonary inflammation (based on measures of sputum and peripheral cytokine levels).
Source: Morris A, Gingo MR, George MP, et al. Cardiopulmonary function in individuals with HIV infection in the antiretroviral therapy era. AIDS 2012;26:731–740.
Does Optimism Affect Risk Behavior Among Gay Men?
Measures of “HIV optimism,” whether health optimism or transmission optimism, can be useful indicators of gay men's likelihood to take risk, but alone are not sufficient to explain how gay men respond to sexual desire and risk behavior. A fuller understanding of the factors affecting gay men's sexual risk-taking behavior also requires individual assessments of technical knowledge, experience, and feelings about pleasure and risk in specific sexual contexts.
Source: Prestage G, Down IA, Bradley J, et al. Is optimism enough? Gay men's beliefs about HIV and their perspectives on risk and pleasure. Sex Transm Dis 2012;39:167–172.
HBV Infection
Good Progress in Preventing Perinatal HBV Infection in United States
Between 1999 and 2008, the incidence of chronic HBV infection among tested infants born to hepatitis B surface antigen (HBsAg)-positive women decreased significantly from 2.1% to 0.8% despite a significant increase in the estimated number of annual births to HBsAg-positive women during that time period. This outcome from the Perinatal Hepatitis B Prevention Program (PHBPP) demonstrates progress in preventing perinatal HBV infections. It is further supported by the finding that the percentage of PHBPP-managed at-risk infants increased from 40.8% to 50.5% on average during this time period, and nearly 95% of the PHBPP-managed infants received hepatitis B immunoglobulin and vaccine within 1 day of birth. However, the percentage of infants who completed the vaccine series by 12 months of age decreased from 86.0% to 77.7% during the course of the study. Important gaps remain in identifying HBsAg-positive pregnant women and in providing appropriate assessment and management of at-risk infants, noted the study authors.
Source: Smith EA, Jacques-Carroll L, Walker TY, et al. The National Perinatal Hepatitis B Prevention Program, 1994–2008. Pediatrics 2012;doi:10.1542/peds.2011–2866.
HPV Infection
Quadrivalent Vaccine Reduces Risk of HPV Disease Recurrence
In a multinational study, more than 17,000 women aged 15–26 years were randomized to receive three doses (at day 1, month 2, and month 6) of either human papillomavirus (HPV) quadrivalent vaccine or placebo. Among the subgroup of women who underwent surgery to excise a cervical intraepithelial neoplasia, the incidence of subsequent HPV-related disease was reduced by 46.2% for the vaccine compared to placebo recipients—22.5% versus 63.2%, respectively. Vaccination was associated with a significant reduction (64.9%) in the risk of subsequent high grade disease of the cervix. The women with previous HPV-related disease, including genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia, had a 13.8% incidence in subsequent HPV-related disease if they received the vaccine and a 51.8% incidence if they received placebo, for a 35.2% reduction in recurrent HPV-related disease with vaccine compared to placebo.
Source: Joura EA, Garland SM, Paavonen J, et al. Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: Retrospective pooled analysis of trial data. Br Med J 2012; doi:10.1136/bmj.e1401.
HPV Infection Lingers in African-American Women
While most women with high-risk HPV infection tend to clear the infection within 9–18 months, a recent study of college students evaluated every 6 months for high-risk HPV status via Pap test found that among the students infected, 56% of African American women were still infected 2 years after the incident infection compared to 24% of European American women. Furthermore, at any visit African-American women were 1.5 times more likely to test positive for high-risk HPV infection than were European-American women. The authors suggest that this increased persistence of high-risk HPV infection may help explain why African American women are 40% more likely to get cervical cancer and 2 times more likely to die from the disease than are European American women. “Although the differences in incidence and mortality rates for cervical cancer between these two groups have been attributed solely to access to care, no study has systematically attempted to identify other factors that may contribute to this disparity.…we suspected that there may be biological factors involved in the immune response to HPV that contribute to the disparity. Our findings support this hypothesis,” concluded the authors.
Source: Abstract presented at the American Association for Cancer Research (AACR) conference, April 1, 2012, Chicago, IL, by Creek KE et al., University of South Carolina, Charleston.