Abstract
HIV Infection
Predicting Tenofovir-Related Risk of Kidney Disease
A newly developed chronic kidney disease (CKD) risk score can predict the 5-year risk of developing CKD in HIV-infected individuals treated with tenofovir. A team of researchers developed the test based on evaluation of a prospective cohort of HIV-infected male veterans who initiated antiretroviral therapy and were followed for a median of 6.3 years. Variables contributing to the CKD risk score included conventional kidney disease risk factors such as age, blood glucose level, systolic blood pressure, hypertension, triglyceride level, and proteinuria, as well as CD4+ cell count. Over 5 years of antiretroviral treatment, CKD occurred in 7.7% of tenofovir users and 3.8% of nonusers. The 5-year CKD risk increased progressively for both groups: from 1% to 16% in nonusers of tenofovir; and from 1.4% to 21.4% among tenofovir users.
Source: Scherzer R, Gandhi M, Estrella MM, et al. A chronic kidney disease risk score to determine tenofovir safety in a prospective cohort of HIV-positive male veterans. AIDS 2014;28:1289–1295.
New US Guidelines Recommend PrEP for At-Risk Groups
On May 14, 2014, the US Public Health Service (USPHS) released the first comprehensive clinical guidelines for pre-exposure prophylaxis (PrEP). On its website, the Centers for Disease Control and Prevention (CDC) describes PrEP as “a way for people who do not have HIV but who are at substantial risk of getting it to prevent HIV infection by taking a pill [Truvada, a combination of tenofovir and emtricitabine] every day.” According to the CDC, “When taken consistently, PrEP has been shown to reduce the risk of HIV infection in people who are at high risk by up to 92%. PrEP is much less effective if it is not taken consistently.” The new USPHS guidelines recommend that HIV-negative individuals who are at substantial risk for HIV consider PrEP. This would include persons who are in an ongoing sexual relationship with an HIV-positive partner, who are not in a mutually monogamous relationship with a partner who recently tested HIV-negative and participate in sexual activity that puts them at substantial risk for HIV transmission, and who inject drugs or have injected illicit drugs or have been in drug treatment for injection drug use during the previous 6 months.
In response to the release of the guidelines came skepticism that physicians would routinely prescribe PrEP, that gay men would tell their physicians they are gay or share information about high-risk behaviors, and that individuals prescribed PrEP would adhere to the daily regimen. PrEP could offer an alternative to condom use for gay men, though protecting only against HIV infection. Sixty-eight AIDS organizations issued a joint statement in support of Truvada use following release of the USPHS recommendations, and criticized the AIDS Healthcare Foundation and its president Michael Weinstein for opposing the prophylactic drug regimen.
If followed, the new PrEP guidelines could increase the number of Truvada presciptions by 50-fold to about 500,000 per year. Most insurers cover the $13,000/year cost of the drug.
Sources: Centers for Disease Control and Prevention. Federal PrEP Guidelines. May 2014. Available at
McNeil Jr DG. Advocating pill, U.S. signals shift to prevent AIDS. The New York Times May 15, 2014.
McNeil Jr DG, Tuller D. AIDS groups back anti-H.I.V. pill amid concerns doctors and patients will resist. The New York Times May 16, 2014.
Global Consortium Formed to Combat Mother-to-Child Transmission
A global consortium comprised of the Ghana Health Service, Yale University, IBM, and the ONE Campaign will partner with local partners in Ghana to reduce the rate of mother-to-child HIV transmission in the country to less than 5% by 2018—and Ghana would like to see that rate drop even further, to less than 1% by 2020. Currently Ghana has one of the highest rates of HIV infection among pregnant women in the world, and 9% of the 800,000 or so babies each year in Ghana are HIV-infected. The consortium is working to establish the information technology infrastructure, coordinate healthcare resource allocations, and build the human capacity needed to help the Ghanaian government—through its national health service and AIDS control program—to meet its goal to “Test, Treat, and Track” all HIV-positive pregnancies in Ghana. Yale pediatric faculty member and co-director of the Ghana–Yale partnership, Dr. Elijah Paintsil, has emphasized the need to educate the public about HIV and available treatments, noting that an important barrier to the delivery of HIV treatment and prevention is the stigma against HIV in Ghana.
Sources: Ghanaian government. Press release: Government to improve maternal, neonatal and childcare for Ghanaians. March 25, 2014. Available at
Yale University. Press release: Yale partners with Ghana to eliminate mother-to-child HIV transmission. March 26, 2014. Available at
Feretic E. Technology is a key ally in the AIDS war. Baseline May 5, 2014. Available at
Risking Unprotected Sex to Have a Baby
In a dramatic change of message, some physicians are telling mixed-status couples that it is now believed to be relatively “safe” to have unprotected sex for the purpose of conception when an HIV-negative woman is ovulating if the HIV-infected partner is on an antiretroviral regimen and has a low to undetectable viral load. For added protection, the uninfected female partner can use pre-exposure prophylaxis (PrEP) to prevent infection if exposed to HIV during unprotected sex during the time she and her HIV-infected partner are trying to conceive. Some physicians believe the risk of viral transmission is too great and the side effects and kidney disease risk associated with PrEP too high and they advise against unprotected sex among serodiscordant couples.
Sources: Cha AE. As mixed-status HIV couples weigh risks, more choose to conceive the old-fashioned way. The Washington Post April 14, 2014.
Protease Inhibitors Linked to Diabetes Risk
A population-based cohort study of 13,632 individuals found that HIV-infected persons receiving combination antiretroviral therapy had a significantly lower risk of diabetes than matched HIV-negative individuals. Within the HIV-infected group, cumulative exposure to protease inhibitors was associated with a significantly increased risk of diabetes, but the association was not significant for exposure to non-nucleoside reverse transcriptase inhibitors. The authors suggest that selection of a combination antiretroviral regimen should consider the cardiometabolic profile of the individual drugs in the therapeutic regimen.
Source: Tripathi A, Liese AD, Jerrell JM, et al. Incidence of diabetes mellitus in a population-based cohort of HIV-infected and non-HIV-infected persons: The impact of clinical and therapeutic factors over time. Diabetic Med 2014;doi:10.1111/dme.12455.
Benefits of Treatment to Limit Microbial Translocation
The results of a study in which macaques with acute SIV infection were treated with sevelamer to bind microbial lipopolysaccharide in the gut and inhibit microbial translocation from the intestinal lumen demonstrate reduced immune activation and inflammation that can damage the intestinal mucosa. The sevelamer-treated monkeys also showed reductions in biomarkers of coagulation, confirming a proposed link between microbial translocation in the gut to the development of cardiovascular comorbidities in SIV-infected nonhuman primates. The study data demonstrated a significant increase in plasma lipopolysaccharide levels in the untreated macaques, especially after acute infection, whereas the levels changed little in the animals treated with sevelamer. Levels of soluble CD14 were used as a surrogate marker of microbial translocation and monocyte activation, and they mirrored those of lipopolysaccharide in the treated and untreated macaques. The authors conclude that early therapeutic intervention to limit microbial translocation may reduce immune activation and inflammation and improve the prognosis of HIV-infected patients.
Source: Kristoff J, Haret-Richter G, Ma D, et al. Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication. J Clin Invest 2014;doi:10.1172/JCI75090.
The Link Between HIV Infection and Fracture Risk
What is the relationship between HIV infection and increased fracture risk, and what role do antiretroviral therapies and impaired bone metabolism play? A large-scale case-control study designed to answer those questions compared the number of HIV-infected individuals in the fracture cohort versus the age- and gender-matched control cohort drawn from the Danish National Health Service registries. Among the more than 124,500 fracture cases, 50 patients had a diagnosis of HIV infection, compared to 52 patients among the approximately 374,000 controls. This corresponds to a significantly increased (threefold higher) risk of fracture among HIV-infected patients. Specifically, the risk of hip, forearm, and spine fractures were significantly increased among the HIV-infected patient cohort.
Source: Prieto-Alhambra D, Güerri-Fernández R, De Vries F, et al. HIV infection and its association with an excess risk of clinical fractures: A nationwide case-control study. J Acq Imm Def Syn 2014;66:90–95.
Human Papilloma Virus Infection
Age and Smoking Linked to Oral HPV
Among 211 individuals identified in the National Health and Nutrition Examination Survey (NHANES) 2009–2010 who were infected with at least one of the 18 high-risk types of oral human papillomavirus (HPV), higher HPV load was significantly associated with older age and intensity of current smoking.
Source: Chaturvedi AK, Graubard BI, Pickard RKL, et al. High-risk oral human papillomavirus load in the US population, National Health and Nutrition Examination Survey 2009–2010. J Infect Dis 2014;doi:10.1093/infdis/jiu116.
Hepatitis C Virus Infection
Efficacy of an Interferon-Free Regimen with/without Ribavirin
A phase 3 study in previously untreated patients with hepatitis C virus (HCV) genotype 1 infection and no cirrhosis showed that a sustained virologic response (SVR) could be achieved using an interferon-free regimen comprised of ABT-450/r, ombitasvir, and dasabuvir with or without ribavirin. The patients received 12 weeks of ABT-450 (150 mg) and ombitasvir (25 mg) once daily and dasabuvir (250 mg twice daily) and either 100 mg of ritonavir or placebo. The primary study endpoint was SVR, defined as an HCV RNA level <25 IU/mL, at the completion of treatment. Virologic failure rates were higher without ribavirin compared to with ribavirin only among patients with genotype 1a infection. SVR rates were 99.5% (with ribavirin) and 99.0% (without ribavirin) for patients with HCV genotype 1b infection, and 97.0% (with ribavirin) and 90.2% (without ribavirin) among patients with genotype 1a infection. Reduced hemoglobin levels occurred significantly more often among patients who received ribavirin.
Source: Ferenci P, Bernstein D, Lalezari J, et al. ABT-450/r-ombitasivir and dasabuvir with or without ribavirin for HCV. N Engl J Med 2014;370:1983–1992.