Abstract
HIV Infection
U.S. Trends in HIV Treatment and Outcomes
Approximately 1.2 million people live with HIV in the U.S. according to the Centers for Disease Control and Prevention (CDC). The North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) has as one of its purposes to monitor trends in the HIV epidemic in the U.S. Focusing on analyses related to HIV treatment and related health outcomes, a recent study reported findings among >45,500 HIV-infected patients treated in NA-ACCORD-participating outpatient clinics in the U.S. between 2000 and 2008.
The authors reported an increase of 9% in the proportion of participants prescribed highly active antiretroviral therapy from 2000 to 2008, with the total rising to 83%. The proportion of individuals with a suppressed viral load increased by 26–72% in 2008, and the median CD4 cell count at death was more than threefold higher (0.209×109 cells/L) in 2008 than in 2000.
Source: Althoff KN, Buchacz K, Hall HI, et al. U.S. trends in antiretroviral therapy use, HIV RNA plasma viral loads, and CD4 T-lymphocyte cell counts among HIV-infected persons, 2000–2008. Ann Intern Med 2012;157:325–335.
Early HAART and Viral Reservoirs in Infants
Highly active antiretroviral therapy (HAART) is recommended for all HIV-infected infants. Nearly 370,000 new HIV infections occur in children each year. To evaluate whether early detection of infection in infants exposed to HIV and early initiation of HAART can limit the development of HIV reservoirs that maintain infection even in the setting of anti-HIV therapy, a team of researchers studied the resting CD4+ T-cell latent HIV reservoir during the first 2 years of life in 17 HIV-infected infants in whom HAART was initiated at a median of 8.1 weeks and suppression of plasma HIV viral load was achieved within 24 weeks of starting treatment.
Resting CD4+ T-cell latent HIV reservoirs were detected in 86% (12 of 14) of the infants at 24 weeks of treatment. Although HIV reservoirs remained measurable throughout the first 2 years of HAART in 60% (6 of 10) of the infants, the reservoir decreased overall from 24 to 96 weeks. The researchers reported a significant relationship between “the frequency of latently infected CD4+ T-cells at 96 weeks of HAART and time to first undetectable plasma viral load.” They concluded that “to minimize HIV reservoirs in infants, rapid curtailment of viremia may limit HIV reservoirs and should be a therapeutic goal of early HAART in infants.”
Source: Persaud D, Palumbo PE, Ziemniak C, et al. Dynamics of the resting CD4+ T-cell latent HIV reservoir in infants initiating HAART less than 6 months of age. AIDS 2012;26:1483–1490.
Positive Results with New Integrase Inhibitor
Preliminary results from the Phase III SINGLE study comparing the experimental integrase inhibitor dolutegravir (50 mg together with abacavir) to treatment with Atripla (a single tablet containing tenofovir/emtricitabine/efavirenz) in treatment-naïve HIV-infected results showed the dolutegravir-based regimen not to be inferior to Atripla in efficacy. In fact, Shionogi-ViiV Healthcare reported that 88% of study participants who received the dolutegravir-based regimen achieved virologic suppression (<50 copies/mL) at 48 weeks of treatment compared to 81% of subjects on Atripla. “Differences in efficacy were primarily driven by a higher rate of discontinuation due to adverse events on the Atripla arm.”
Source: Press release: Shionogi-ViiV Healthcare announces positive initial data from phase III study of dolutegravir-based regimen vs Atripla in HIV. July 11, 2012. Available at:
Predicting the Impact of Generic HIV Drugs
Currently, the average annual cost of HIV treatment approaches $20,000/patient. Much of the cost for HIV care and medications is paid for by the government and, in 2012 in the U.S., that bill will total about $15 billion, which does not cover all HIV-infected individuals, many of whom go untreated. The upcoming expiration of patents on some of the most commonly used anti-HIV drugs will help reduce these costs as generic versions come on the market. During the next 5 years, patents on several HIV drugs will expire, including the nucleoside reverse transcriptase inhibitors abacavir (in 2012) and FTC/emtricitabine (2015), non-nucleoside reverse transcriptase inhibitors efavirenz and delavirdine (both in 2013), protease inhibitors darunavir and tipranavir (in 2015) and ritonavir (in 2016), and the nucleotide reverse transcriptase inhibitor tenofovir (2017). For example, the three-in-one co-formulated pill Atripla will be replaced by two generic and one brand-name drugs, a switch that could save the U.S. government an estimated $920 million overall. There is a risk of reduced effectiveness of an antiretroviral regime that requires patients to take three pills instead of one due to adherence issues, although the difference would not likely be substantial. The article quotes Michael Weinstein, president of the AIDS Healthcare Foundation, a Los Angeles, CA-based advocacy organization as predicting that, “In ten years this will be a disease treated for $200 per year, or less.”
Source: Maxmen A. Generic HIV drugs will widen US treatment net. Nature 2012;488:267.
Serosorting Not Always Protective
Among a group of nearly 6,700 men who have sex with men (MSM) without a prior HIV diagnosis who were seen in a sexually transmitted disease clinic in Seattle, WA, from 2001 to 2010, serosorting–the practice of either selecting sex partners or deciding to using condoms depending on a sex partner's perceived HIV status–was associated with a reduced risk of testing HIV positive compared to MSM who did not practice serosorting and reported having unprotected anal intercourse with partners of opposite or unknown HIV status among white and Hispanic MSM. Serosorting was not associated with a reduced risk of HIV transmission among the African American MSM in this study, however.
Source: Golden, MR, Dombrowski J, Kerani RP, Stekler JD. Failure of serosorting to protect African American men who have sex with men from HIV infection. Sex Trans Dis 2012;39:659–664.
Effects of Hiding a Child's HIV Diagnosis
A study aimed at evaluating the immunological and virological impact of hiding a perinatally infected child's or adolescent's HIV-positive status relied on self-reporting of diagnosis disclosure to friends and medication hiding, and compared these variables to three medical outcomes: CD4+ absolute count, CD4+ percentage, and viral load. The results indicated an association between diagnosis disclosure to at least one friend with less medication hiding, and this was related to higher CD4+ absolute counts and percentages, but was not associated with viral load. The children and adolescents who shared their HIV-positive status with 11 or more (compared to 1–10) friends were even less likely to report medication hiding and to have higher CD4+ absolute counts, indicative of better immune function.
Source: Calabrese SK, Martin S, Wolters PL, et al. Diagnosis disclosure, mediation hiding, and medical functioning among perinatally infected, HIV-positive children and adolescents. AIDS Care 2012; 24:1092–1096.
ART and IRIS Risk in Patients with Tuberculosis
According to recent estimates, about 1.37 million people worldwide are co-infected with HIV and tuberculosis. Although multiple studies support a substantial survival benefit with early ART initiation among patients with HIV and tuberculosis who have a CD4+ count less than 0.050×109 cells/L, co-treatment of HIV and tuberculosis carries an increased risk for immune reconstitution inflammatory syndrome (IRIS). The Starting Antiretroviral Therapy at Three Points in Tuberculosis (SAPiT) trial, based on a study of 642 patients with HIV-related tuberculosis treated at an outpatient clinic in South Africa as part of a randomized, open-label clinical trial, compared IRIS incidence, severity, and outcomes depending on the timing of ART initiation. The three treatment groups were identified as “early integrated” (ART initiated within 4 weeks of the start of tuberculosis treatment), “late integrated” (ART initiated within 4 weeks of completion of the intensive phase of tuberculosis therapy), or “sequential treatment” (ART initiated within 4 weeks after completion of tuberculosis treatment). IRIS incidence was 19.5, 7.5, and 8.1 per 100 person-years in the three treatment groups, respectively; and among patients with a baseline CD4+ count <0.050×109cells/L it was 45.5, 9.7, and 19.7 per 100 person-years, respectively. Furthermore, IRIS cases in the early integrated treatment group tended to be more severe than in the other two groups, and patients in the early integrated group who were affected by IRIS had significantly higher hospitalization rates and longer time to resolution than did patients in the other two groups.
The authors of the study concluded that, “In light of the higher IRIS-associated morbidity with early ART in tuberculosis treatment, the decision on the timing of ART in co-infected patients should be influenced by baseline CD4+ cell counts because of the association between risk for IRIS and reported morbidity and mortality benefit by CD4+ cell count strata. Thus, in patients with a CD4+ count less than 0.050×109 cells/L, the balance of benefit and risk would favor initiation of ART within 4 weeks of tuberculosis treatment initiation. On the other hand, in patients with a CD4+ count of 0.050×109 cells/L or greater, the decision of early versus later initiation of ART during tuberculosis treatment must be weighed against the availability of clinical capacity to diagnose and manage IRIS. … in patients with a CD4+ count greater than 0.050×109 cells/L, although ART initiation may be deferred for 8 to 12 weeks after tuberculosis treatment initiation, every effort should be made to initiate ART no later than 12 weeks after tuberculosis treatment initiation.”
Source: Naidoo K, Nonhlanhia Y-Z, Padayatchi N, et al. The immune reconstitution inflammatory syndrome after antiretroviral therapy initiation in patients with tuberculosis: findings from the SAPIT trial. Ann Intern Med 2012;157:313–324.
HPV Infection
HPV Vaccination Rates Among American Teens
Since 2005, the Centers for Disease Control and Prevention (CDC) has included a three-dose immunization against human papillomavirus (HPV) in the schedule of routine vaccinations for adolescents 11–12 years of age. According to data from the National Immunization Survey-Teen (NIS-Teen), from 2010 to 2011 vaccination coverage among females for one or more doses of HPV increased from 48.7% to 53.0%, and for three or more doses from 32.0% to 34.8%. Among teen girls who began the HPV series, 70.7% received all three doses, whereas among teen boys who initiated vaccination, 28.1% completed the three immunizations. During the survey period, HPV vaccine initiation was higher for blacks and Hispanics compared with whites among both females and males; however, completion of three or more doses was only higher for Hispanics compared with whites. Among females, completion of the HPV series after initiation was lower for blacks compared with whites. A comparison of HPV vaccination based on poverty status revealed that coverage with at least one dose or at least three doses of HPV vaccine was higher for girls and boys living below the poverty level compared with those living at or above the poverty level. Among teen girls, however, completion of the HPV series was lower among those living below the poverty level compared to those living at or above the poverty level.
Source: Dorell C, Stokley S, Yankey D, et al. (Centers for Disease Control and Prevention). National and state vaccination coverage among adolescents aged 13–17 years–United States, 2011. MMWR 2012; 61:671–677.