Abstract
HIV Infection
Promising Results for HIV Pre-Exposure Prophylaxis with Long-Acting Integrase Inhibitor
A long-acting preventive antiretroviral agent that could be dosed quarterly might overcome adherence issues associated with pre-exposure prophylaxis (PrEP) that requires daily dosing. Macaques were administered the integrase strand-transfer inhibitor GSK744—formulated as a long-acting injectable for monthly to quarterly dosing—in two doses. The first injection was given 1 week before initial SIV exposure and the second dose was administered 4 weeks later. The macaques received low-dose viral challenge weekly for 8 weeks. All animals were protected from infection by plasma concentrations of the integrase inhibitors that could be achieved in humans with quarterly injections. In a second experiment, macaques received only one dose of GSK744 1 week before viral challenge, and virus was then administered until infection occurred. The decline in protection correlated with decreasing plasma drug levels.
Source: Andrews CD, Spreen WR, Mohri H, et al. Long-acting integrase inhibitor protects macaques from intrarectal simian/human immunodeficiency virus. Science 2014;343:1151–1154.
Renal Risk of FTC/TDF PrEP
To assess the renal safety of tenofovir disoproxil fumarate (TDF) used in combination with emtricitabine (FTC) for pre-exposure prophylaxis, the Iniciativa Profilaxis Pre-Exposición (iPrEx) study randomly assigned HIV-seronegative men and transgender women who have sex with men to receive oral daily FTC/TDF or placebo. Measurements of renal function included serum creatinine and phosphorus both during and discontinuation of treatment, and estimation of creatinine clearance (CrCl). Compared to the placebo group, those receiving FTC/TDF had a small but significant decrease in CrCl from baseline that began at 4 weeks of treatment and continued until PrEP was stopped, when it resolved. Patient race, age, or history of hypertension did not have a role on the effect of FTC/TDF on CrCl. The study authors conclude that this “very mild nonprogressive decrease in CrCl that was reversible” could be managed with routine serum creatinine monitoring.
Source: Solomon MM, Lama JR, Glidden DV. Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis. AIDS 2014;28:851–859.
CVD Risk in Perinatal HIV Infection
A quarter to half of perinatally HIV-infected adolescents evaluated for susceptibility to atherosclerosis in the coronary arteries and abdominal aorta have an increased risk factor burden for cardiovascular disease (CVD) risk, according to a recent study. Of the 165 study participants, 48% had increased coronary artery CVD risk and 24% had an increased abdominal artery risk factor burden. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) risk scores represented a weighted combination of modifiable risk factors, including dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. “PDAY scores may be useful in identifying high-risk youth who may benefit from early lifestyle or clinical interventions,” conclude the authors.
Sources: Patel K, Wang J, Jacobson D, et al. Aggregate risk of cardiovascular disease among adolescents perinatally infected with the human immunodeficiency virus. Circulation 2013;doi:10.1161/circulationaha.113.001978.
Protease Inhibitors Linked to Cerebral Small Vessel Disease
The toxic effects of chronic exposure to protease inhibitors in ART may increase a patient's risk of developing cerebral small vessel disease (CSVD), which can contribute to HIV-associated neurocognitive disorders (HAND) and the resulting neurocognitive impairment. Possible pathologic mechanisms include direct toxicity of protease inhibitors to cerebral small vessels or indirect effects on CSVD by inducing metabolic abnormalities. A study of HIV-infected adults in the California NeuroAIDS Tissue Network demonstrated an association between both mild and moderate/severe CSVD with protease inhibitor-based ART after adjusting for diabetes mellitus, a link between moderate/severe CSVD and diabetes after adjusting for ART exposure, and a correlation between HAND and mild CSVD.
Source: Soontornniyomkij V, Umlauf A, Chung SA, et al. HIV protease inhibitor exposure predicts cerebral small vessel disease. AIDS 2014;doi:10.1097/QAD.0000000000000262.
Trends in Advanced Disease at ART Initiation in Africa
Between 2006–2011, the proportion of HIV-infected patients who had advanced disease (CD4+ count <100 cells/μL) on initiation of antiretroviral therapy (ART) decreased from 42% to 29% in Kenya, Mozambique, Rwanda, and Tanzania, based on a study of more than 334,000 adults, about 149,000 of whom initiated ART during that period. The median CD4+ count at ART initiation increased from 125 to 185 cells/μL during the 5-year study period. Other trends identified included an increasing sex disparity in advanced HIV disease at ART initiation, with the odds higher among men (adjusted odds ratio 1.4) at the end of the study, as well as advanced disease more likely among those on tuberculosis treatment and those with a 12-month or longer gap in care before initiating ART.
Source: Lahuerta M, Wu Y, Joffman S, et al. Advanced HIV disease at entry into HIV care and initiation of antiretroviral therapy during 2006–2011: findings from four sub-saharan African countries. Clin Infect Dis 2014;58:432–441.
Persistent Immunosuppression Despite Viral Load Suppression
A study exploring persistent immunosuppression despite viral suppression on ART included 400 patients from the UK Collaborative HIV Cohort Study who began ART who were on at least a three-drug regimen, had pre-ART CD4+ cell counts <100 cells/μL, achieved viral load suppression (≤50 copies/ml) by 9 months after starting ART, maintained viral suppression throughout the 2- to 5-year post-ART initiation follow-up period, and had regular access to care. Based on the results, the study authors concluded the following: individuals with a pre-ART CD4+ cell count <100 cells/μL who survive and maintain consistent viral load suppression on ART have “a 90% chance of reaching a CD4+ cell count above 200 cells/μL by 3 years.” They reported that of the participants with a median pre-ART CD4+ cell count of 38 (14–65) cells/μL, 2 (0.5%), 8 (2%), 28 (7%), 131 (33%), and 259 (65%) did not achieve a CD4+ cell count of more than 100, 150, 200, 350, and 500 cells/μL, respectively, by 2–5 years from the start of ART.
Source: O'Connor JL, Smith CK, Lampe FC, et al. Failure to achieve a CD4+ cell count response on combination antiretroviral therapy despite consistent viral load suppression. AIDS 2014;28:919–924.
Which Latency-Reversing Agents Will Be Effective?
The main hurdle to HIV eradication is the persistence of latent viral reservoirs despite ART. A new ex vivo assay being used to evaluate experimental latency-reversing agents (LRAs)—designed to purge latent reservoirs without activating T lymphocytes—has shown that none of the LRAs tested, all histone deacetylase (HDAC) inhibitors, induced HIV transcription from the latent reservoirs of patients on ART. This suggests that LRAs that do not activate T cells do not induce substantial increases in HIV mRNA in patient's cells. Based on these findings, the authors conclude that “current in vitro models do not fully recapitulate mechanisms governing HIV-1 latency in vivo. Further, our data indicate that non-activating LRAs are unlikely to drive the elimination of the latent reservoir in vivo when administered individually.”
Source: Bullen CK, Laird GM, Durand CM, et al. New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo. Nature Med 2014;doi:10.1038/nm.3489.
Racial Differences in Patient-Provider Communication on ART Adherence
The conversations between providers and patients about adherence to antiretroviral regimens may differ depending on whether the patient is white, African American, or Hispanic, and these differences could negatively affect HIV care and outcomes, suggest the authors of a study in AIDS and Behavior. Based on coding of transcripts of routine outpatient visits, the study authors concluded that providers tended to dominate the conversation more with African-American patients than with others, and made more directive statements when discussing antiretroviral treatment with Hispanics. While they noted more discussion about ARV adherence overall with African-American and Hispanic patients, specific strategies to improve adherence were missing from the discussion. The authors suggest more specific problem solving and more discussion rather than directiveness as areas for improvement.
Source: Laws MB, Lee Y, Rogers WH, et al. Provider-patient communication about adherence to anti-retroviral regimens differs by patient race and ethnicity. AIDS Behav 2014;doi:10.1007/s10461-014-0697-z.
Using Social Media to Map HIV Risk
A study led by researchers at the David Geffen School of Medicine at UCLA explored the potential to use real-time “big data” gathered from social media sites to improve HIV prevention and detection efforts. The focus was on understanding how individuals communicate sexual risk behaviors on social networking sites such as Twitter, and specifically discussed methods to collect and assess geolocated conversations about HIV risk behaviors, how to characterize the prevalence and content of those conversations, and the feasibility of using HIV risk-related communications as a means of detecting HIV outcomes. They collected and filtered more than 550 million tweets from 2012 using HIV risk-related key words, extracted more than 9,800 geolocated tweets and mapped them by location, and reported a significant positive correlation between HIV-related tweets and HIV cases. The authors suggest that the collection and evaluation of real-time social networking data offers a feasible method for evaluating and detecting HIV risk behaviors and outcomes.
Source: Young SD, Rivers C, Lewis B. Methods of using real-time social media technologies for detection and remote monitoring of HIV outcomes. Prev Med 2014; available at
Female-to-Female Sexual HIV Transmission
In a rare case of female-to-female sexual transmission of HIV laboratory testing confirmed that the viruses infecting the two women in the previously HIV-discordant couple who had a 6-month monogamous relationship when the newly infected partner acquired HIV were virtually identical and had ≥98% sequence identity in three genes. The couple reported routine unprotected oral and vaginal contact, use of insertive sex toys, and sexual activity at times accompanied by bleeding.
Source: Chan SK, Thornton LR, Chronister KJ, et al. Likely female-to-female sexual transmission of HIV—Texas, 2012. Mortal Morbid Weekly Report 2014;63:209–212.
HCV Infection
Infection Prevalence Estimate in US
Based on National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2010, the estimated prevalence of hepatitis C virus (HCV) infection in the US during that time period was 1.0%, corresponding to 2.7 million chronically infected persons. Characteristics and risk factors associated with HCV infection were age 40–59 years, male gender, non-Hispanic black, less education, lower family income, illicit drug use including injection drugs, and receipt of a blood transfusion before 1992.
Source: Denniston MM, Jiles RB, Drobeniuc J, et al. Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med 2014;160:293–300.
Hepatic Decompensation Risk in Mono- vs. HIV Co-Infection
The incidence of hepatic decompensation among individuals co-infected with HIV and HCV is significantly greater (7.4%) than among persons with HCV mono-infection (4.8%), even if the HIV-infected patients are receiving ART and have HIV RNA levels below 1,000 copies/mL, according to a recent retrospective cohort study. For co-infected patients, rates of liver decompensation tended to be higher in the presence of accompanying advanced liver fibrosis, severe anemia, diabetes, and if the individual's racial group was non-black.
Source: Lo Re III V, Kallan MJ, Tate JP, et al. Hepatic Decompensation in antiretroviral-treated patients co-infected with HIV and hepatitis C virus compared with hepatitis C virus-monoinfected patients: a cohort study. Ann Intern Med 2014;160:369–379.
Sexually Transmitted Infections
Rising STI Rates Among MSM in Ireland
As reported in the British Telegraph, levels of sexually transmitted infections (STIs) are reaching “crisis levels” in Northern Ireland, and the rising rates may be attributable to the availability of increasingly effective treatments for HIV infection, leading men who have sex with men (MSM) to have more unprotected sex. In 2012, for example, 222 MSM in Northern Ireland received a diagnosis of gonorrhea, representing 65% of all gonorrhea-infected males in the country—an increase from 9% in 2000. The article identifies syphilis as another growing problem. It also cites the results of a recent survey organized by the British Association for Sexual Health and HIV, which found that more than 25% of gay and bisexual men have never been tested for STIs.
Source: STI Rtes among men who have sex with men continue to increase in Northern Ireland, despite education and information campaigns by the local health authorities. Belfast Telegraph March 12, 2014. Available at
Gay Dating Apps Driving Rise in Syphilis
A near doubling (15–29) of cases of syphilis in Onondaga County, NY, from 2012 to 2013, and the 30% increase in syphilis cases recorded overall in New York outside of New York City during that period, is being attributed to the proliferation of gay dating phone apps that men can use to find sex partners more easily. Furthermore, it is more difficult, if not impossible, for public health officials to locate the anonymous sex partner(s) of infected persons if they meet through a phone app. In 2013, nearly all of the syphilis cases in New York occurred in men, and more than 70% of those involved men who have sex with men.
Source: Mulder JT. Spike in syphilis in Onondaga County and across state blamed on gay dating apps.