HIV Screening Accurate, ART Reduces Risks, but Gaps Remain

22-11-2012 21:47

HIV screening is accurate and antiretroviral therapy (ART) reduces risk for AIDS-defining events, deaths, and sexual transmission in adolescents and adults with less serious immunodeficiency, according to a study published online November 19 in the Annals of Internal Medicine. ART also reduces risk for mother-to-child transmission of the HIV virus in some pregnant women, although it may increase risk for preterm delivery, according to a second study also published online November 19 in the same journal.

Roger Chou, MD, from the Oregon Evidence-based Practice Center and Oregon Health & Science University in Portland, and colleagues conducted 2 reviews: one included randomized trials and observational studies in nonpregnant adolescents and adults, and a second included randomized trials and cohort studies in pregnant women.

The researchers set out to update the 2005 reviews by the US Preventive Services Task Force (USPSTF), which found that HIV screening is accurate and that ART can lead to clinical benefits in adolescents and adults with advanced disease, and to update the concurrent report that prenatal HIV screening is accurate and can reduce the risk for mother-to-child transmission through interventions for pregnant women. In 2005, the USPSTF recommended HIV screening for all adolescents and adults who have increased risk for infection (persons reporting HIV risk factors or evaluated in settings with HIV prevalence of >1%) and screening for all pregnant women at their first prenatal visit unless they decline.

According to the Centers for Disease Control and Prevention, incidence of HIV infections in the United States is approximately 50,000 cases per year, and research ( AIDS. 2006;20:1447-1450) has shown that about 20,000 of those cases are thought to be derived from transmission from persons who do not know they are infected.

Nonpregnant Adolescents and Adults

For nonpregnant adolescents and adults, the researchers sought to determine whether studies performed since 2004 found that any benefits are derived from universal or targeted screening, with universal defined as routine testing of all people aged 13 to 64 years unless setting prevalence of HIV is less than 0.1% and targeted defined as screening of persons in settings with prevalence higher than 1%.

The authors also studied whether screening yielded different numbers of new diagnoses at different intervals, how effective behavioral counseling is, how effective ART is in reducing transmission, what the effects of ART initiation are at different CD4 thresholds, and what the effects of longer-term treatment of ART are.

They found that no studies had evaluated the effect of either screening in general or screening at different intervals on clinical outcomes. Six of 7 observational studies found that ART produced a lower risk for HIV transmission than that seen in untreated persons (pooled hazard ratio [HR], 0.34; confidence interval [CI], 0.13 - 0.92; I 2, 73%). Little evidence still exists on the effects of behavioral counselling.

"New studies included in this update provide strong evidence for the effectiveness of initiating ART at CD4 counts between 0.350 and 0.500 × 10 9 cells/L, although evidence showing benefits is less consistent for ART initiation at greater than 0.500 × 10 9 cells/L," the researchers write.

Although long-term ART with some older protease inhibitors was still found to be associated with increased risk for cardiovascular harm, "ART use is associated with a 10- to 20-fold reduction in risk for sexual transmission," the researchers write.

In conclusion, they add, "The main area of discrepancy between HIV screening guidelines is whether to routinely screen populations not known to be at increased risk. Screening tests for HIV are highly accurate, but targeted screening misses a substantial proportion of infected persons because of undisclosed or unknown risk factors. Evidence published since the 2005 USPSTF review shows highly beneficial effects of ART for reducing sexual transmission of HIV and risk for AIDS-defining events and death in persons with less immunologically advanced stages of disease."

Pregnant Women

In addition to the questions probed for the nonpregnant population, the researchers also studied whether the pregnant population had adverse effects such as false-positive test results and anxiety from rapid vs standard HIV testing in asymptomatic pregnant women. They also sought to determine whether newer ART regimens reduced mother-to-child transmission; whether ART for HIV-positive pregnant women had effects on long-term morbidity, mortality, or qualify of life; and whether ART during pregnancy caused any mother or child harm.

They found that no studies since 2005 had evaluated the effects of screening vs no screening on risk for mother-to-child infection and on clinical outcomes and that no trial evaluated whether 1-time screening or repeated screening yielded different results. As for potential false-positive findings, a single study found that the predictive diagnostic value of the rapid test was greater (90%) than for the standard immunoassay test (74%).

"New cohort studies of antiretroviral therapy in nonbreastfeeding women in the United States and Europe confirm the finding from the 2005 USPSTF review that full-course combination antiretroviral therapy is effective at reducing for the rate of mother-to-child transmission (<1% to 2.4% vs. 9% to 22% with no antiretroviral therapy)," the researchers write.

No study since 2005 had evaluated any effects of ART during pregnancy on morbidity, mortality, or quality of life, and evidence "remains sparse" on whether any long-term maternal harms are associated with ART during pregnancy or continued afterward, the researchers write.

"Receipt of antiretroviral therapy during pregnancy is associated with the nonobstetric adverse events typically associated with the specific drugs and regimens, but these often resolve after treatment with the offending drug or drug combination is stopped, and effective alternatives are usually available," the researchers write.

The authors conclude, "[P]renatal HIV screening is accurate and antiretroviral therapy for combination with avoidance of breastfeeding and cesarean section in women with HIV RNA levels greater than 1000 copies/mL near the time of delivery is effective at reducing risk for mother-to-child transmission."

Although some ARTs may be associated with preterm delivery, the authors call for more research to confirm both short- and long-term effects.

Limitations of both studies include the fact that only English-language publications were reviewed. They also included observational studies, which could be more susceptible to bias than randomized clinical trials, and they included studies from "resource-poor and high-prevalence settings" that may not be generalizable to US practice.

This research was supported by the Agency for Healthcare Research and Quality. Some of the authors or their institutions have received other payments or funding from the Agency for Healthcare Research and Quality.

Ann Intern Med. Published online November 19, 2012.