Background Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy. Methods We tested the hypothesis that the timing of ART initiation would significantly affect mortality among adults not previously exposed to antiretroviral drugs who had newly diagnosed tuberculosis and CD4+ T-cell counts of 200 per cubic millimeter or lower. After beginning the standard, 6-month treatment for tuberculosis, patients were randomly assigned to either earlier treatment (2 weeks after beginning tuberculosis treatment) or later treatment (8 weeks after) with stavudine, lamivudine, and efavirenz. The primary end point was survival. Results A total of 661 patients were enrolled and were followed for a median of 25 months. The median CD4+ T-cell count was 25 per cubic millimeter, and the median viral load was 5.64 log10 copies per milliliter. The risk of death was significantly reduced in the group that received ART earlier, with 59 deaths among 332 patients (18%), as compared with 90 deaths among 329 patients (27%) in the later-ART group (hazard ratio, 0.62; 95% confidence interval [CI]; 0.44 to 0.86; P = 0.006). The risk of tuberculosis-associated immune reconstitution inflammatory syndrome was significantly increased in the earlier-ART group (hazard ratio, 2.51; 95% CI, 1.78 to 3.59; P<0.001). Irrespective of the study group, the median gain in the CD4+ T-cell count was 114 per cubic millimeter, and the viral load was undetectable at week 50 in 96.5% of the patients. Conclusions Initiating ART 2 weeks after the start of tuberculosis treatment significantly improved survival among HIV-infected adults with CD4+ T-cell counts of 200 per cubic millimeter or lower. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis and the National Institutes of Health; CAMELIA ClinicalTrials.gov number, NCT01300481.)

No abstract

West-central African chimpanzees (Pan troglodytes troglodytes) harbor strains of simian immunodeficiency virus (SIVcpz) that are closely related to all three groups of human immunodeficiency virus 1 (HIV-1) (M, N, and 0) and have thus been implicated as a A reservoir for human infection (1). Yet, because all SIVcpz strains identified to date have been derived from captive chimpanzees, little is known about the prevalence, geographic distribution, and genetic diversity of SIVcpz in the wild. B Here, we describe a prevalence study g9 and detection of SIVcpz in wild-living 9 apes.Sampling blood from endangered pri-c mates is generally neither feasible nor ethical. We therefore developed noninvasive methods to detect and characterize SIVcpz in wild chimpanzees by analyzing fecal and urine samples for SIVcpz antibodies and virion RNA (2). The sensitivity of antibody detection by enhanced chemilu-Fig minescent immunoblot was tested in cap-ze tive chimpanzees of known HIV-l1/SIVcpz Re infection status and found to be 100% for in urine and 65% for feces (specificity in (6 each instance was 100%). The sensitivity lik ofpolymerase chain reaction amplification sic of virion RNA from feces of SIVcpz-in-rec fected chimpanzees was 66%. Using these de techniques, we studied 28 P. t. verus from the Tai Forest, Cote d'Ivoire, 24 P. t. schweinfurthii from Kibale National Park, Uganda, and 6 P. t. schweinfurthii from Gombe National Park, Tanzania (Fig. 1A). Of the 58 wild-living chimpanzees tested, only one healthy 23-year-old sexually active male (Ch-06) from Gombe was positive for SIVcpz infection. Two different urine samples from Ch-06 contained SIVcpz antibodies (Fig. 1B), and three fecal samples were positive for SIVcpz virion RNA. Sequence analysis of a 2195-base pair pol/vif fragment amplified from fecal samples revealed a highly divergent SIVcpz strain (TAN1) that differed from west-central African SIVcpz and HIV-1 groups M, N, and O by 28 to 30% of amino acid sequences. The most similar sequence was SIVcpzANT from a captive P. t. schwein-furthii (3), which differed by 23%. In a phylogenetic tree, SIVcpzTAN1 and SIVcpzANT clustered together in a statistically highly significant manner (Fig. 1C).. . u B, p31 I .,-SIVcpzCAM3 J1~l. SIV'cpzUS _I SIVcpzGAB1 SIVcpzANT g. 1. (A) Locations of Tai, Kibale, and Gombe chimpa es and the four recognized chimpanzee subspecies ( d asterisks indicate the origins of four captive SIVcI ected P. t. troglodytes apes (6, 7). (B) Urine immur )ts of Ch-06, two infected captive chimpanzees CAP ) and ch-No (3), and negative samples. (C) Maxim elihood tree of TAN1 Pol/Vif sequences (GenBank accE >n number AF382822) and other SIVcpz (P. t. troglodyt d; P. t. schweinfurthii, blue) and HIV-1 strains (asteri. note >95% bootstrap values). The discovery of SIVcpzTAN1 in a single wild-living Gombe chimpanzee provides insight into the origins and evolutionary history of HIV-1 and SIVcpz. First, the geographic boundaries for SIVcpz must now be extended from Gabon and Cameroon in west-central Africa to the ea...

We investigated two mitochondrial genes (cytb and cox1), one plastid gene (tufA), and one nuclear gene (ldh) in blood samples from 12 chimpanzees and two gorillas from Cameroon and one lemur from Madagascar. One gorilla sample is related to Plasmodium falciparum, thus confirming the recently reported presence in gorillas of this parasite. The second gorilla sample is more similar to the recently defined Plasmodium gaboni than to the P. falciparum-Plasmodium reichenowi clade, but distinct from both. Two chimpanzee samples are P. falciparum. A third sample is P. reichenowi and two others are P. gaboni. The other chimpanzee samples are different from those in the ape clade: two are Plasmodium ovale, and one is Plasmodium malariae. That is, we have found three human Plasmodium parasites in chimpanzees. Four chimpanzee samples were mixed: one species was P. reichenowi; the other species was P. gaboni in three samples and P. ovale in the fourth sample. The lemur sample, provisionally named Plasmodium malagasi, is a sister lineage to the large cluster of primate parasites that does not include P. falciparum or ape parasites, suggesting that the falciparum + ape parasite cluster (Laverania clade) may have evolved from a parasite present in hosts not ancestral to the primates. If malignant malaria were eradicated from human populations, chimpanzees, in addition to gorillas, might serve as a reservoir for P. falciparum.T here is a revolution afoot concerning our understanding of human malaria. It was shown in 1994/1995 that the closest relative of Plasmodium falciparum, the agent of malignant malaria was Plasmodium reichenowi, a chimpanzee parasite, the only ape malaria parasite that had been molecularly characterized (1-4). The close phylogenetic relationship between P. falciparum and Plasmodium reichenowi, their distinctness from the three other known human malaria parasites (Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae), as well as from other primate parasites, and their remoteness from bird or lizard parasites, was soon confirmed by other studies (5-7). It was assumed, as a working hypothesis, that P. falciparum and P. reichenowi had evolved from a common ancestor parasite, independently in their respective hosts, humans and chimpanzees, as these two lineages gradually diverged from one another over the last 5-7 million years-the cospeciation hypothesis. Two alternative hypotheseseither (i) a human origin (P. reichenowi evolved from an introduction of P. falciparum into chimpanzee hosts) or (ii) a chimpanzee origin (P. falciparum evolved from the introduction of P. reichenowi into the human lineage)-could not be tested against each other or against the cospeciation hypothesis, because only one P. reichenowi isolate was available, which had been isolated from a captive chimpanzee.It was soon demonstrated by Rich et al. (8), Rich and Ayala (9), and Ayala and Rich (10) that P. falciparum has very low levels of neutral genetic polymorphism, a result that was subsequently confirmed by other investigators (11...