Y THE END OF 2006, AN ESTImated 2.3 million children worldwide were living with human immunodeficiency virus type 1 (HIV-1). 1 Although most children acquire the virus through largely preventable mother-to-child transmission, roll-out of perinatal HIV prevention services has been sluggish worldwide. As a result, each day more than 1000 children become newly infected. 2 Without treatment, approximately half will die by their second birthday 3 ; however, lives can be extended and morbidity avoided with combination antiretroviral therapy (ART). In Zambia, recent progress has been made toward reducing new pediatric infections through aggressive scale-up of perinatal HIV prevention services. 4 Despite these efforts, 130 000 children are Author Affiliations are listed at the end of this article.

Plasmodium falciparum causes the most severe form of malaria in humans. An important class of drugs in malaria treatment is the sulfone͞sulfonamide group, of which sulfadoxine is the most commonly used. The target of sulfadoxine is the enzyme dihydropteroate synthase (DHPS), and sequencing of the DHPS gene has identified amino acid differences that may be involved in the mechanism of resistance to this drug. In this study we have sequenced the DHPS gene in 10 isolates from Thailand and identified a new allele of DHPS that has a previously unidentified amino acid difference. We have expressed eight alleles of P. falciparum PPPK-DHPS in Escherichia coli and purified the functional enzymes to homogeneity. Strikingly, the K i for sulfadoxine varies by almost three orders of magnitude from 0.14 M for the DHPS allele from sensitive isolates to 112 M for an enzyme expressed in a highly resistant isolate. Comparison of the K i of different sulfonamides and the sulfone dapsone has suggested that the amino acid differences in DHPS would confer cross-resistance to these compounds. These results show that the amino acid differences in the DHPS enzyme of sulfadoxine-resistant isolates of P. falciparum are central to the mechanism of resistance to sulfones and sulfonamides.

Background Young men who have sex with men (YMSM) are a key population for implementation of PrEP interventions. This open-label study examined adherence to PrEP and assessed sexual behavior among a diverse sample of YMSM in 12 U.S. cities. Methods Eligible participants were 18–22 year old HIV-uninfected MSM who reported HIV transmission risk behavior in the past 6 months. Participants were provided daily TDF/FTC (Truvada®). Study visits occurred at baseline, monthly through week 12, then quarterly through week 48. Dried blood spots (DBS) were serially collected for the quantification of tenofovir diphosphate (TFV-DP). Results Between March-September 2013, 2186 individuals were approached and 400 were found to be preliminarily eligible. Of those 400, 277 were scheduled for an in-person screening visit and 200 were enrolled (mean age=20.2; 54.5% Black, 26.5% Latino). Diagnoses of sexually transmitted infections (STIs), including urethral and rectal chlamydial/gonococcal infection and syphilis, at baseline was 22% and remained high across visits. At week 4, 56% of participants had TFV-DP levels consistent with ≥4 pills/week. By week 48, 34% of participants had TFV-DP levels consistent with ≥4 pills/week, with a noticeable drop-off occurring at Week 24. Four HIV seroconversions occurred on study (3.29/100 person-years). Condomless sex was reported by >80% of participants and condomless anal sex with last partner was associated with higher TFV-DP levels. Conclusions Acceptability of PrEP was high and most participants achieved protective drug levels during monthly visits. As visit frequency decreased, so did adherence. YMSM in the US may need PrEP access in youth-friendly settings with tailored adherence support and potentially augmented visit schedules.

Adherence to highly active antiretroviral therapy (HAART) was investigated among HIV-infected adolescents recruited from 13 US cities into the REACH (Reaching for Excellence in Adolescent Care and Health) project, the first large-scale disease progression study of HIV-positive adolescents infected through sexual behaviour or injection drug use. Of 161 subjects, 7% could not correctly identify all their prescribed medications; 11% could identify them but reported never taking at least one medication. The majority (83%) reported taking all of their medications at least some of the time, but only 50% of these subjects reported full adherence. Therefore, only 41% of the sample reported full adherence. A strong association was found between adherence and reduced viral load. A CD4 level of > or = 500 cells/mm3 was also associated with adherence. Higher levels of depression were significantly associated with decreased adherence, and a trend was found for an association between number of medications prescribed and adherence. Strict adherence to HAART is critical for sustained suppression of viral replication allowing for immune recovery and reducing the risk of the selection of antiviral resistance. Adherence appears to be a serious problem among HIV-positive adolescents. Better education, intervention to relieve depression, and efforts to improve ease of medication use are essential.