Abstract
HIV Infection
Drug-Resistant HIV on the Rise in Europe
Transmission of HIV with drug resistance mutations (TDRs) increased by an estimated 35% in Europe during the period 2008–2010 compared to 2003–2005. This rise in the total number of people infected with drug-resistant HIV in 26 European countries occurred even as the prevalence of HIV drug resistance remained stable at about 10% across these time periods. The overall HIV rose throughout Europe during these years. The most common mutations (5.1%) were associated with resistance to nucleoside reverse transcriptase inhibitors (NRTIs), followed by 3.7% for non-NRTIs (NNRTIs), and 2.3% for protease inhibitors (PIs). The number of new diagnoses with NNRTI-resistance mutations increased from 336 to 550 from 2003–2005 to 2008–2010. The study authors noted this to be “of particular concern, considering these mutations generally confer high-level resistance to NNRTIs that are frequently used as first-line therapy.
Source: Hofstra M, Sauvageot N, Albert J, et al. Increasing number of HIV-1 diagnoses with transmitted drug resistance across Europe despite stable prevalence. Presented at the 14th European AIDS Conference, Brussels, Belgium, October 17, 2013. Available at
Trends in Drug-Resistant HIV Detection in Europe
Data from the EuroSIDA 1997–2012 study reveal trends in drug resistance among participants who experienced virological failure (VF). Among the study subjects with VF throughout the study period, only 26.5% had at least one test for drug resistance within the first few months after detection of VF. The proportion of the population being followed for VF dropped significantly over the course of the study, from 75.2% in 1997 to 6.2% in 2012. Despite declines in VF and resistance testing over time, the study authors reported detection of resistance (≥1 mutation) in a high proportion of tests (75.8% overall): 69.9% to NRTI; 44.9% to NNRTI; 44.0% to PI.
Source: Schultz A, Phillips AN, Paredes R, et al. Prevalence of detected drug resistance across different regions of Europe: Data from EuroSIDA 1997–2012. Presented at the 14th European AIDS Conference, Brussels, Belgium, October 17, 2013. Available at
Documentary Traces Roots of AIDS Pandemic
The HBO documentary film “The Battle of amfAR,” which premiered December 2, 2013, recounts the true story of the early days of AIDS and how two women, actress Elizabeth Taylor and researcher Dr. Mathilde Krim, worked together to create AmfAR, the first AIDS research foundation. The film chronicles the organization's history and its continuing importance and role in the fight against HIV/AIDS. Directors Rob Epstein and Jeffrey Friedman use new and archival interviews, news broadcasts, time lapse fluorescence microscopy, and animation to educate viewers on the historical, political, scientific, and social events and perspectives surrounding the emergence and spread of the disease and the stigma it engendered. Jeffrey Laurence, MD, Editor of this Journal, is prominently featured in the documentary.
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Good Anti-HIV Activity for CCR5 Inhibitor
The results of a Phase 2b 48-week study comparing cenicriviroc (CVC) with efavirenz (EFV) together with emtricitabine/tenofovir (FTC/TDF) in treatment-naive HIV-infected adults with CCR5-tropic virus demonstrated virologic success (HIV RNA <50 c/mL of 68% for the CVC 100 mg treatment group, 64% for CVC 200 mg, and 50% for EFV). Virologic non-response was highest in the CVC 200 mg group (20%), followed by CVC 100 mg (15%), and EFV (11%). NRTI resistance mutations were only linked to CVC use and were twice as prevalent in the 200 mg treatment group as in the 100 mg group. The study authors suggest continued development of cenicriviroc, which represents a new class of HIV therapeutics. CVC is a CCR5/CCR2 inhibitor that blocks the CCR5 co-receptor, inhibiting HIV entry into cells, and the CCR2 receptor, which has a role in inflammation. In the study described here a relatively high number of subjects dropped out, presumably due to the complex dosing regimen of CVC used in the clinical trial. However, a new formulation of the drug should make it easier to use.
Sources: Feinberg J, Thompson M, Cade J, et al. Final week 48 analysis of cenicriviroc (CVC) compared to efavirenz (EFV), in combination with emtricitabine/tenofovir (FTC/TDF), in treatment-naive HIV-1-infected adults with CCR5-tropic virus. Presented at the 14th European AIDS Conference, Brussels, Belgium, October 17, 2013. Available at
Highleyman L. CCR5 inhibitor cenicriviroc shows good activity against HIV. HIV and Hepatitis. October 18, 2013. Available at
Higher Attrition Rates for Young Adults in HIV Care
Based on data collected from 160 HIV clinics in Kenya, Mozambique, Tanzania, and Rwanda, young people ages 15–24 years tend to have substantially higher antiretroviral (ART) attrition rates both before and after antiretroviral (ART) initiation than other age groups. Within this group, nonpregnant young women had lower pre-ART and post-ART attrition rates than young men. Youths attending clinics that offered more adolescent-friendly services, such as sexual and reproductive health services including condoms, or adolescent support groups, had reduced attrition and, in particular, significantly lower attrition rates after ART initiation.
Source: Lamb MR, Fayorsey R, Nuwagaba-Birbonwoha H, et al. High attrition before and after ART initiation among youth (15–24 years of age) enrolled in HIV care. AIDS 2013; doi: 10.1097/QAD.0000000000000054.
Long-Term, Stable HIV Incidence Rate Among Injection Drug Users
Relatively early in the global HIV epidemic, in the late 1980s, Australia instituted free and legal Needle and Syringe Programs (NSPs), and by 1991 6.3 million syringes were being distributed annually to about 62,000 regular users of injectable drugs of abuse. Whereas the number of people who inject drugs in Australia is believed to have doubled between 1991 and 1999, the number of syringes distributed annually increased 5-fold to 30.5 million. The success of the NSPs has likely contributed substantially to the very low, sustained HIV incidence among people who inject drugs in Australia for nearly 20 years. A retrospective study involving repeat respondents to a national, annual sero-survey to estimate the incidence of HIV among people who inject drugs reported an HIV incidence of 0.11 per 100 person-years over the period 1995–2012. Most of the HIV infections occurred among drug injectors who identified as men who have sex with men (MSM).
Source: Iversen J, Wand H, Topp L, et al. Extremely low and sustained HIV incidence among people who inject drugs in a setting of harm reduction. AIDS 2013; doi: 10.1097/QAD.0000000000000068.
Rising Costs of 2nd and 3rd Line Antiretroviral Drugs
To approximate the cost of HIV care in the US, data collected on two groups of patients were analyzed: one from the MarketScan Commercial Claims and Encounters Database covering 2007–2011; and one from the MarketScan Lab Database Covering 2007–2010. The second group of data included CD4 measurements. For most subjects, ART began with a NNRTI, usually efavirenz, followed by a protease inhibitor, an integrase inhibitor, various third agents, and then a CCR5 antagonist. ART was the biggest HIV-related health care expense for these individuals, whether first-line (54.4%), second-line (52.2%), or third-line therapy (47.8%). The findings demonstrate that in the US, second-line ART costs 24% more per year than first-line therapy, and third-line treatment costs 41% more than first-line therapy. The proportion of expenses that went for antiretroviral medications rose from 6.6% for first-line therapy to 7.5% for second-line therapy, to 13.2% for third-line therapy. Analysis of the cohort for which there was CD4 data showed that unadjusted costs per person-month were highest for people with initial CD4 counts ≤100 cells/μL, at $5,573. The cost-per-month of ART dropped substantially at higher CD4 levels and did not differ much as CD4 measurements increased: $2,508 for CD4 100–200 cells/μL; $2,425 for 201–350 cells/μL; $2,820 for 351–500 cells/μL; and $2,571 for >500 cells/μL.
Source: Mascolini M. Second- and third-line ART cost 24% and 41% more than first line in US. National AIDS Treatment Advocacy Project report on Abstract H-662 presented at the 53rd ICAAC Interscience Conference on Antimicrobial Agents and Chemotherapy, September 10–13, 2013, Denver, CO: Solect CG, Snedecor SJ, Khachatryan A, et al. Burden of illness in a US commercially-insured HIV population: Treatment patters and costs. Report available at
Comparing Cause of Death and Timing of ART Initiation
A study designed to compare the cause of death among HIV-infected individuals, taking into consideration their CD4 cell count at time of ART initiation, with cause-specific mortality among HIV-uninfected individuals, found that HIV-infected persons in whom ART is initiated earlier are more likely to die of non-AIDS causes and at older ages, compared to those who began ART later in the course of the infection. When divided into three subgroups based on timing of ART initiation, 78% of early initiators (CD4 cell count >350 cells/μL) died of non-AIDS causes; 74% of the intermediate group (CD4 cell count 201–350 cells/μL); and 49% of the late group (CD4 cell count <200 cells/μL). Early initiators of ART died at a median age of 72 years, the intermediate cohort died at a median age of 69, and the median age of death for late initiators was 66 years. Among HIV-infected individuals who died of non-AIDS causes, for each CD4 cell count category, the cohort's median age at death was younger than the 75 years estimated for the HIV-uninfected group. The study authors noted in particular that on multivariable analysis adjusted hazard ratios for non-AIDS death among HIV-uninfected individuals and early initiators of ART were nearly identical (hazard ratio 1.01), suggesting “the possibility of reducing the risk of non-AIDS mortality among HIV-infected individuals to approximate that faced by comparable HIV-uninfected individuals.”
Source: Wada N, Jacobson LP, Cohen M, et al. Cause-specific mortality among HIV-infected individuals, by CD4+ cell count at HAART initiation, compared with HIV-uninfected individuals. AIDS 2013; doi: 10.1097/QAD.0000000000000078.
AIDS-Defining Illnesses Decline as CD4 Counts Rise
An international team of researchers reporting for the Opportunistic Infections Working Group on behalf of the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study in EuroCOORD, described more than 12,000 AIDS-defining illnesses (ADIs) that occurred among more than 207,500 HIV-infected persons ages 14 years or older between 1998 and 2010 who had at least one CD4 cell count of ≥200 μL. The authors showed that incidence rates of ADIs decreased from 20.5 per 1000 person-years of follow-up (PYFU) with a current CD4 cell count of 200–349 cells/μL to 4.1 per 1000 PYFU with a current CD4 cell count ≥1000 cells/μL. Within that broad range, ADI rates were significantly higher for persons with CD4 counts of 500–749 cells/μL compared to 750–999 cells/μL, but did not continue to decline further as CD4 counts increased beyond 1000 cells/μL. These findings were consistent whether individuals had high or low viral loads.
Source: Mocroft A, Furrer HJ, Miro JM, et al. The incidence of AIDS-defining illnesses at a current CD4 count ≥200 cells/μL in the post-combination antiretroviral therapy era. Clin Infect Dis 2013;57:1038–1047.