***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus ( HIV ) among men who have sex with men ; however , the efficacy among heterosexuals is uncertain . METHODS We r and omly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine ( TDF-FTC ) or matching placebo once daily . Monthly study visits were scheduled , and participants received a comprehensive package of prevention services , including HIV testing , counseling on adherence to medication , management of sexually transmitted infections , monitoring for adverse events , and individualized counseling on risk reduction ; bone mineral density testing was performed semiannually in a subgroup of participants . RESULTS A total of 1219 men and women underwent r and omization ( 45.7 % women ) and were followed for 1563 person-years ( median , 1.1 years ; maximum , 3.7 years ) . Because of low retention and logistic limitations , we concluded the study early and followed enrolled participants through an orderly study closure rather than exp and ing enrollment . The TDF-FTC group had higher rates of nausea ( 18.5 % vs. 7.1 % , P<0.001 ) , vomiting ( 11.3 % vs. 7.1 % , P=0.008 ) , and dizziness ( 15.1 % vs. 11.0 % , P=0.03 ) than the placebo group , but the rates of serious adverse events were similar ( P=0.90 ) . Participants who received TDF-FTC , as compared with those who received placebo , had a significant decline in bone mineral density . K65R , M184V , and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment . In a modified intention-to-treat analysis that included the 33 participants who became infected during the study ( 9 in the TDF-FTC group and 24 in the placebo group ; 1.2 and 3.1 infections per 100 person-years , respectively ) , the efficacy of TDF-FTC was 62.2 % ( 95 % confidence interval , 21.5 to 83.4 ; P=0.03 ) . CONCLUSIONS Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults . The long-term safety of daily TDF-FTC prophylaxis , including the effect on bone mineral density , remains unknown . ( Funded by the Centers for Disease Control and Prevention and the National Institutes of Health ; TDF2 Clinical Trials.gov number , NCT00448669 . ) Background : Some studies have detected associations between in utero antiretroviral therapy ( ARV ) exposure and birth defects but evidence is inconclusive . Methods : A total of 2202 human immunodeficiency virus (HIV)-exposed children enrolled in the Pediatric AIDS Clinical Trials Group 219 and 219 C protocol s before 1 year of age were included .  Birth defects were classified using the Metropolitan Atlanta Congenital Defects Program coding . Logistic regression models were used to evaluate associations between first trimester in utero ARV exposure and birth defects . Results : A total of 117 live-born children had birth defects  for a prevalence of 5.3 % ( 95 % confidence interval [ CI ] : 4.4 , 6.3 ) . Prevalence did not differ by HIV infection status or overall ARV exposure ; rates were 4.8 % ( 95 % CI : 3.7 , 6.1 ) and 5.8 % ( 95 % CI : 4.2 , 7.8 ) in children without and with first trimester ARV exposure , respectively . The defect rate was higher among children with first trimester efavirenz exposure ( 5/32 , 15.6 % ) versus children without first trimester efavirenz exposure ( adjusted odds ratio [ aOR ] = 4.31 [ 95 % CI : 1.56 , 11.86 ] ) . Protective effects of first trimester zidovudine exposure on musculoskeletal defects were detected ( aOR = 0.24 [ 95 % CI : 0.08 , 0.69 ] ) , while a higher risk of heart defects was found ( aOR = 2.04 [ 95 % CI : 1.03 , 4.05 ] ) . Conclusions : The prevalence of birth defects was higher in this cohort of HIV-exposed children than in other pediatric cohorts . There was no association with overall ARV exposure , but there were some associations with specific agents , including efavirenz . Additional studies are needed to rule out confounding and to evaluate newer ARV agents BACKGROUND The most effective highly active antiretroviral therapy ( HAART ) to prevent mother-to-child transmission of human immunodeficiency virus type 1 ( HIV-1 ) in pregnancy and its efficacy during breast-feeding are unknown . METHODS We r and omly assigned 560 HIV-1-infected pregnant women ( CD4 + count , > or = 200 cells per cubic millimeter ) to receive coformulated abacavir , zidovudine , and lamivudine ( the nucleoside reverse-transcriptase inhibitor [ NRTI ] group ) or lopinavir-ritonavir plus zidovudine-lamivudine ( the protease-inhibitor group ) from 26 to 34 weeks ' gestation through planned weaning by 6 months post partum . A total of 170 women with CD4 + counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine-lamivudine ( the observational group ) . Infants received single-dose nevirapine and 4 weeks of zidovudine . RESULTS The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery ( 96 % in the NRTI group , 93 % in the protease-inhibitor group , and 94 % in the observational group ) or throughout the breast-feeding period ( 92 % in the NRTI group , 93 % in the protease-inhibitor group , and 95 % in the observational group ) . By 6 months of age , 8 of 709 live-born infants ( 1.1 % ) were infected ( 95 % confidence interval [ CI ] , 0.5 to 2.2 ) : 6 were infected in utero ( 4 in the NRTI group , 1 in the protease-inhibitor group , and 1 in the observational group ) , and 2 were infected during the breast-feeding period ( in the NRTI group ) . Treatment-limiting adverse events occurred in 2 % of women in the NRTI group , 2 % of women in the protease-inhibitor group , and 11 % of women in the observational group . CONCLUSIONS All regimens of HAART from pregnancy through 6 months post partum result ed in high rates of virologic suppression , with an overall rate of mother-to-child transmission of 1.1 % . ( Clinical Trials.gov number , NCT00270296 . BACKGROUND We studied the effect of pregnancy on atazanavir pharmacokinetics in the presence and absence of tenofovir . METHODS This was a non-r and omized , open-label , multicentre Phase IV study in HIV-infected pregnant women recruited from European HIV treatment centres . HIV-infected pregnant women treated with boosted atazanavir ( 300/100 mg or 400/100 mg atazanavir/ritonavir ) as part of their combination antiretroviral therapy ( cART )  were included in the study . 24 h pharmacokinetic curves were recorded in the third trimester and postpartum . Collection of a cord blood and maternal sample at delivery was optional . RESULTS 31 patients were included in the analysis , 21/31 patients used  tenofovir as part of cART . Median ( range ) gestational  age at delivery was 39 weeks ( 36 - 42 ) . Approaching delivery 81 % ( 25 patients ) had an HIV viral load < 50 copies/ml , all < 1,000 copies/ml . Least squares means ratios ( 90 % CI ) of atazanavir  pharmacokinetic parameters third trimester/postpartum were : 0.66 ( 0.57 , 0.75 ) for AUC0 - 24h , 0.70 ( 0.61 , 0.80 ) for Cmax and 0.59 ( 0.48 , 0.72 ) for C24h . No statistical difference in pharmacokinetic parameters was found between patients using tenofovir versus no tenofovir . None of the patients showed atazanavir concentrations < 0.15 mg/l ( target for treatment-naive patients ) . One baby had a congenital abnormality , which was not likely to be related to atazanavir/ritonavir use . None of the children were HIV-infected . CONCLUSIONS Despite 34 % lower atazanavir exposure during pregnancy , atazanavir/ritonavir 300/100 mg once daily generates effective concentrations for protease inhibitor (PI)-naive patients , even if co-administered with tenofovir . For treatment-experienced patients ( with relevant PI resistance mutations ) therapeutic drug monitoring of atazanavir should be considered to adapt the atazanavir/ritonavir dose on an individual basis . Clinical Trials.gov number NCT00825929 IMPORTANCE Most studies examining the association of prenatal antiretroviral ( ARV ) exposures with congenital anomalies ( CAs ) in children born to human immunodeficiency virus (HIV)-infected women have been reassuring , but some evidence suggests an increased risk with specific ARV agents . OBJECTIVE To evaluate the association of in utero ARV exposures with CAs in HIV-exposed uninfected children . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study design . The Pediatric HIV/AIDS Cohort Study 's Surveillance Monitoring of ART Toxicities ( SMARTT ) Study was performed at 22 US medical centers among 2580 HIV-exposed uninfected children enrolled in the SMARTT Study between March 23 , 2007 , and June 18 , 2012 . EXPOSURES First-trimester exposure to any ARV and to specific ARV medications . MAIN OUTCOMES AND MEASURES The primary end point was a CA based on physician review of infant physical examinations according to the Antiretroviral Pregnancy Registry modification of the Metropolitan Atlanta Congenital Defects Program . Rates of CAs were estimated overall and by birth year . Logistic regression models were used to evaluate the association of CAs with first-trimester ARV exposures , adjusting for demographic and maternal characteristics . RESULTS Congenital anomalies occurred in 175 of 2580 children , yielding a prevalence of 6.78 % ( 95 % CI , 5.85%-7.82 % ) ; 242 major CAs were confirmed , including 72 musculoskeletal and 55 cardiovascular CAs . The prevalence of CAs increased significantly among successive birth cohorts ( 3.8 % for children born before 2002 and up to 8.3 % for those born 2008 - 2010 ) . In adjusted models , no association of first-trimester exposures with CAs was found for any ARV , for combination ARV regimens , or for any drug class . No individual ARV in the reverse transcriptase inhibitor drug classes was associated with an increased risk of CAs . Among protease inhibitors , higher odds of CAs were observed for atazanavir sulfate ( adjusted odds ratio [ aOR ] , 1.95 ; 95 % CI , 1.24 - 3.05 ) and for ritonavir used as a booster ( aOR , 1.56 ; 95 % CI , 1.11 - 2.20 ) . With first-trimester atazanavir exposure , risks were highest for skin ( aOR , 5.23 ) and musculoskeletal ( aOR , 2.55 ) CAs . CONCLUSIONS AND RELEVANCE Few individual ARVs and no drug classes were associated with an increased risk of CAs  in HIV-exposed infants after adjustment for calendar year and maternal characteristics . While the overall risk remained low , a relative increase was observed in successive years and with atazanavir exposure . Given the low absolute CA risk , the benefits of recommended ARV therapy use during pregnancy still outweigh such risks , although further studies are warranted ABSTRACT The objective of this study was to investigate for the first time tenofovir ( TFV ) pharmacokinetics in plasma and peripheral blood mononuclear cells ( P BMC s ) of the neonate . HIV-1-infected pregnant women received two tablets of tenofovir disoproxil fumarate ( TDF ; 300 mg ) and emtricitabine ( FTC ; 200 mg ) at onset of labor and then one tablet daily for 7 days postpartum . A single dose of 13 mg/kg of body weight of TDF 
    Output:
    
Conclusions : TDF-based ART in pregnancy seems generally safe for women and their infants .