CROI 2012, the annual Conference on Retroviruses and Opportunistic Infections, took place from March 5-8 in Seattle. The features below highlight just some of the studies that emerged from the conference.
Can Circumcision Decrease Herpes Risk?
Deferred Vs Immediate ART in Children
Reducing Risk in Partners of HIV-Positive Individuals
Monthly HIV Prophylaxis Appears Promising
Sustaining Virologic Responses in HIV-HCV Coinfection
The Particulars: Previous research has shown that males who undergo circumcision can help reduce their risk of contracting HIV infection. Less is known about additional long-term effects of circumcision with regard to the transmission of other infectious diseases.
Data Breakdown: Investigators conducted a study of men in a South African town before and after a roll-out of a circumcision project. The prevalence of circumcision increased from 15.6% to 49.4% among those aged 15 to 49. The prevalence of herpes simplex virus-2 (HSV-2) among uncircumcised men was 30.8%, compared with 17.1% among circumcised men. Circumcision led to a 27.0% reduction in the risk of acquiring HSV-2.
Take Home Pearl:Circumcision appears to reduce the risk of contracting HIV infection and also significantly reduces the likelihood of contracting HSV-2 among recipients of the procedure.
The Particulars: Immediate antiretroviral therapy (ART) during infancy has been shown to benefit HIV-infected babies. However, this treatment strategy may put HIV-infected babies at risk for drug side effects and resistance to available treatments, among other potential concerns.
Data Breakdown: A study of infants who received immediate ART found that those who stopped treatment after 1 to 2 years appeared to fare significantly better than those in whom ART was delayed until signs of illness or a weakened immune system were observed. Among those who stopped therapy after 2 years, 33% remained well; 25% of those who stopped treatment after 1 year remained well. In a separate study, researchers compared immediate and deferred treatment in children aged 2 to 12 who were not diagnosed with HIV during infancy but who presented for treatment when they became mild or moderately sick. Findings from the second analysis indicated that the two patient groups experienced comparably low disease progression rates. However, the immediate treatment group experienced higher rates of drug toxicities and resistance. Problems in neurologic development occurred with equivalent frequency in both groups.
Take Home Pearls: Immediate treatment in HIV-infected infants appears to preserve the immune system as well as healthy brain development. When treatment during infancy is missed, both delayed and immediate ART in older children with HIV who become ill appear to provide health benefits but do not prevent neurologic damage.
The Particulars: When one partner of a heterosexual couple is HIV-positive, these couples face difficult decisions regarding individual treatment, risk, and risk decision-making when pregnancy is desired. When the HIV-positive partner is unable to or does not want to start treatment, offering therapy to the HIV-negative partner may be useful.
Data Breakdown: A controlled trial enrolled nearly 5,000 couples in whom the HIV-positive partner was not yet eligible for treatment. HIV-negative partners were randomized to placebo, tenofovir, or tenofovir plus emtricitabine. When compared with placebo, tenofovir reduced HIV risk by 67% for the HIV-negative partner. The tenofovir plus emtricitabine combination yielded the best results, reducing risk for the HIV-negative partner by 75%.
Take Home Pearls: Administration of antiretroviral drugs to HIV-negative people in a heterosexual relationship appears to reduce their risk of acquiring the virus from an HIV-positive partner. Further study on the subject matter is warranted.
The Particulars: Research on HIV pre-exposure prophylaxis (PrEP) in women has provided mixed results in clinical trials. The efficacy of PrEP appears to be dependent on adherence to dosing. With a small dose required to suppress HIV, rilpivirine may be particularly suitable for a once-monthly injection as PrEP.
Data Breakdown: Rilpivirine was administered as a single intramuscular dose at 300 mg, 600 mg, and 1200 mg in 27 healthy women and at 600 mg in six healthy men in a study. Pharmacokinetics in plasma, the female genital tract, and the male rectum were explored over 84 days. Prolonged plasma and genital tract exposure were observed with all doses. All doses were well tolerated, with no serious adverse events.
Take Home Pearls: A once-a-month intravenous formulation of rilpivirine appears to be maintained at levels that should protect recipients against infection. All three PrEP doses analyzed in the study appeared to be well tolerated. The safety of multiple doses requires further investigation.
The Particulars: In 2011, the FDA approved the first direct-acting hepatitis C virus (HCV) agents, leading to a new era of treatment. Two protease inhibitors— telaprevir and boceprevir—are approved for use in HCV mono-infected patients. Studies are ongoing in patients coinfected with HIV and HCV.
Data Breakdown: An investigation of telaprevir in combination with pegylated interferon/ribavirin in previously untreated HIV-HCV coinfected patients with difficult-to-treat HCV indicated that 74% of patients who took telaprevir achieved sustained virologic response at 12 weeks after treatment completion (SVR12), compared with 45% of those on pegylated interferon/ribavirin alone. A separate study randomly assigned a similar patient population to boceprevir 800 mg three times daily or placebo plus 1.5 mcg/kg/week pegylated interferon alfa-2b. Of participants in the boceprevir arm, 61% achieved SVR12, compared with 27% in the placebo arm.
Take Home Pearl: In HIV-HCV coinfected patients, the addition of a first-generation HCV protease inhibitor to pegylated interferon/ribavirin appears to dramatically increase the likelihood of achieving a sustained virologic response when measured at 12 weeks.