Abstract
HIV and AIDS
Free Retail-Based HIV Testing Program
The Centers for Disease Control and Prevention (CDC) estimates that 1.1 million people in the U.S. are living with HIV, and nearly 20% do not know they are infected. To expand HIV testing, the CDC initiated a 2-year, $1.2 million pilot program to offer HIV testing through 24 select community pharmacies and retail clinics. The CDC will use the results from this program, to be implemented across urban and rural areas, to develop a model that pharmacists and nurse practitioners (NPs) can use to implement HIV testing more broadly nationwide. Testing is free, and participating pharmacists and NPs are trained to deliver the confidential test results and to provide counseling. In the event of a preliminary positive result, the individual will be referred to a local health care provider for confirmatory testing and follow-up care and given a list of supporting community-based organizations.
War on Drugs Fueling HIV Pandemic
The Global Commission on Drug Policy released a report entitled “The War on Drugs and HIV/AIDS: How the Criminalization of Drug Use Fuels the Global Pandemic,” in which it states that “repressive drug law enforcement practices force drug users away from public health services” and into environments where HIV risk is markedly elevated. Also contributing to increased HIV risk is mass incarceration of non-violent drug offenders, and the report notes that in the U.S. as many as 25% of HIV-infected Americans may pass through correctional facilities annually, with disproportionate incarceration rates being a key factor in the elevated HIV rates among African Americans in particular. The Commission also faults the war on drugs for causing policy distortion in many countries, a factor that has led to poor or absent implementation of evidence-based addition treatment, HIV prevention, and public health measures. Furthermore, the war on drugs has failed to control drug supplies, with continuing evidence of falling drug prices and increasing drug potency based on U.S. drug surveillance data.
The Global Commission offers several recommendations, including to “replace ineffective measures focused on the criminalization and punishment of people who use drugs with evidence-based and rights-affirming interventions proven to meaningfully reduce the negative individual and community consequences of drug use.” In addition, it urges “countries that under-utilize proven public health measures to “scale up evidence-based strategies to reduce HIV infection and protect the health of persons who use drugs, including sterile syringe distribution and other safer injecting programs.” The Commission recommends that national and world leaders “measure drug policy success by indicators that have real meaning in communities, such as reduced rates of transmission of HIV and other infectious diseases (e.g., hepatitis C), fewer overdose deaths, reduced drug market violence, fewer individuals incarcerated and lowered rates of problematic substance use.”
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New Four-Drug Tablet as Effective as Ritonavir-Boosted Regimen
A phase 3, double-blind, randomized trial has shown that a once-daily single tablet of co-formulated elvitegravir (EVG), cobicistat (COBI), embricitabine (ETC), and tenofovir disoproxil fumarate (TDF), known as “Quad,” is not inferior to the current international standard of care for initial therapy of treatment-naïve HIV-1-infected patients. EVG is an HIV integrase strand transfer inhibitor and COBI is a CYP3A4 inhibitor. The trial subjects had an HIV-1 RNA concentration ≥5,000 copies/mL, and the primary study endpoint was an HIV-1 RNA concentration <50 copies/mL after 48 weeks with a 12% non-inferiority margin. The once-daily, single-tablet regimen was not inferior to treatment with ritonavir-boosted atazanavir (ATV/RTV) and emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and had a safety and tolerability profile comparable to the currently recommended dual-pill initial treatment regimen, which also presents potential ritonavir-associated metabolic complications.
Source: DeJesus E, Rockstroh JK, Henry K, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritnoavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: A randomised, double-blind, phase 3, non-inferiority trial. The Lancet 2012 379:2429–2438.
Positive Results with Single-Tablet Four-Drug Regimen
Among the preferred therapeutic regimens that combine at least three antiretroviral drugs for use in treatment-naïve HIV-infected patients, only one is co-formulated as a single tablet. It combines efavirenz (EFV), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) and is considered the gold standard for initial treatment, but may also carry an increased risk for rash, central nervous system side effects, and hyperlipidemia compared with some other therapeutic options. A phase 3 trial comparing an experimental four-drug, once-daily, integrase-based regimen, known as “Quad,” demonstrates that it is not inferior to EFV/FTC/TDF. The four-drug co-formulated tablet contains elvitegravir (EVG), an integrase inhibitor, cobicistat (COBI), a CYP3A4 inhibitor, emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF). The trial compared the two regimens in patients with a screening HIV RNA concentration ≥5,000 copies/mL and had a primary endpoint of <50 copies/mL at week 48.
Source: Sax PE, DeJesus E, Mills A, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: A randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. The Lancet 2012;379:2439–2448.
PrEP Trial Stopped Due to Lack of Efficacy
A trial comparing preexposure prophylaxis (PrEP) with combination tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) was stopped early due to lack of efficacy. Among more than 2,100 HIV-negative women in Kenya, South Africa, and Tanzania randomly assigned to receive once-daily TDF/FTC or placebo to prevent HIV infection, the incidence rate was 4.7 and 5.0 per 100-person years, respectively, in the two treatment groups. Compliance with the TDF/FTC regimen was poor, and the treatment was associated with more side effects than placebo. It is likely that the failure of this trial and its early conclusion, in contrast with two successes with the same regimen (reported in the two briefs to follow), was due to failure to comply with the pill regimen. This conclusion is based on data showing a correlation between blood levels of TDF and protection against HIV acquisition.
Source: Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. New Engl J Med 2012;DOI:10.1056/NEJMoa1202614.
PrEP Significantly Reduces Infection Risk
HIV-negative heterosexual men and women given antiretroviral-based preexposure prophylaxis (PrEP) were significantly less likely than those given placebo to become infected during the study period, with infection rates of 1.2 and 3.1 per 100 person-years for those receiving tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) versus placebo, respectively. The study population of seronegative men and women in Botswana also received comprehensive prevention services. The TDF/FTC group had higher rates of mild side effects than the placebo group, a similar rate of serious adverse events, and a significantly greater decrease in bone mineral density. The trial was ended early due to low retention and logistic issues.
Source: Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 2012;DOI:10.1056/NEJMoa1110711.
HIV-Negative Heterosexual Partner Protected with PrEP
Preexposure prophylaxis with once-daily tenofovir (TDF) or combination TDF-emtricitabine (TDF-FTC) was effective compared to placebo in preventing infection in HIV-negative men and women partners in heterosexual serodiscordant couples. In a study of more than 4,700 couples in Kenya and Uganda followed monthly for up to 36 months, the infection incidence rates were 0.65, 0.50, and 1.99 per 100 person-years for the TDF, TDF/FTC, and placebo treated groups, respectively, yielding a relative reduction of 67% with TDF and of 75% with TDF/FTC. The protective effects of TDF and TDF/FTC did not differ significantly.
Source: Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. New Engl J Med 2012;DOI:10.1056/NEJMoa1108524.
Expanded Access to Treatment in Africa
UNAIDS reports that in 2011 an additional 1.1 million HIV-infected individuals in sub-Saharan Africa received antiretroviral therapy, and treatment reached a total of 6.2 million people in the region last year. That figure represents a greater than 100-fold increase in access to HIV treatment in sub-Saharan Africa in less than 10 years. Contributing to this greater access to treatment has been the decrease in costs of HIV medication regimens, with a year's supply of first-line therapy that would have cost about $10,000 in 2000 now costing less than $100/person. Early estimates suggest that the greatest progress in expanded access to antiretroviral therapy has been achieved in South Africa, Zimbabwe, and Kenya.
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High Rate of HIV Diagnoses at First Test
According to a review of HIV incidence surveillance data for the period 2006–2009, among adults and adolescents for whom testing history information is available, 41% were diagnosed with HIV infection at their first HIV test and 59% had a negative test at some point before their HIV diagnosis. The relatively high percentage of individuals who had never been tested before receiving an HIV diagnosis points to the need for increased annual HIV testing for at-risk populations to increase early detection. The groups with the highest percentage of persons with an HIV-negative test result ≤12 months before HIV diagnosis included those aged 13–29 years (33%), males with HIV transmission resulting from male-to-male sexual activity (29%), and whites (28%).
Source: Centers for Disease Control and Prevention. Previous HIV testing among adults and adolescents newly diagnosed with HIV infection—national HIV surveillance system, 18 jurisdictions, United States, 2006–2009. MMWR 2012;61:441–445.