BACKGROUNDUniversal antiretroviral therapy (ART) with annual population testing and a multidisease, patient-centered strategy could reduce new human immunodeficiency virus (HIV) infections and improve community health. METHODSWe randomly assigned 32 rural communities in Uganda and Kenya to baseline HIV and multidisease testing and national guideline-restricted ART (control group) or to baseline testing plus annual testing, eligibility for universal ART, and patient-centered care (intervention group). The primary end point was the cumulative incidence of HIV infection at 3 years. Secondary end points included viral suppression, death, tuberculosis, hypertension control, and the change in the annual incidence of HIV infection (which was evaluated in the intervention group only). RESULTSA total of 150,395 persons were included in the analyses. Population-level viral suppression among 15,399 HIV-infected persons was 42% at baseline and was higher in the intervention group than in the control group at 3 years (79% vs. 68%; relative prevalence, 1.15; 95% confidence interval [CI], 1.11 to 1.20). The annual incidence of HIV infection in the intervention group decreased by 32% over 3 years (from 0.43 to 0.31 cases per 100 personyears; relative rate, 0.68; 95% CI, 0.56 to 0.84). However, the 3-year cumulative incidence (704 incident HIV infections) did not differ significantly between the intervention group and the control group (0.77% and 0.81%, respectively; relative risk, 0.95; 95% CI, 0.77 to 1.17). Among HIV-infected persons, the risk of death by year 3 was 3% in the intervention group and 4% in the control group (0.99 vs. 1.29 deaths per 100 person-years; relative risk, 0.77; 95% CI, 0.64 to 0.93). The risk of HIV-associated tuberculosis or death by year 3 among HIV-infected persons was 4% in the intervention group and 5% in the control group (1.19 vs. 1.50 events per 100 person-years; relative risk, 0.79; 95% CI, 0.67 to 0.94). At 3 years, 47% of adults with hypertension in the intervention group and 37% in the control group had hypertension control (relative prevalence, 1.26; 95% CI, 1.15 to 1.39). CONCLUSIONSUniversal HIV treatment did not result in a significantly lower incidence of HIV infection than standard care, probably owing to the availability of comprehensive baseline HIV testing and the rapid expansion of ART eligibility in the control group. (Funded by the National Institutes of Health and others; SEARCH ClinicalTrials.gov number, NCT01864603.

Significant motor and cognitive deficits were found in HIV-infected ART-naive Ugandan children with CD4 cell counts of ∼350 cells/μL and percentages of >15%. Study of whether early initiation of ART could prevent or reverse such deficits is needed.

Background Human immunodeficiency virus (HIV) protease inhibitors show activity against Plasmodium falciparum in vitro. We hypothesized that the incidence of malaria in HIV-infected children would be lower among children receiving lopinavir–ritonavir–based antiretroviral therapy (ART) than among those receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)–based ART. Methods We conducted an open-label trial in which HIV-infected children 2 months to 5 years of age who were eligible for ART or were currently receiving NNRTI-based ART were randomly assigned to either lopinavir–ritonavir–based ART or NNRTI-based ART and were followed for 6 months to 2 years. Cases of uncomplicated malaria were treated with artemether–lumefantrine. The primary end point was the incidence of malaria. Results We enrolled 176 children, of whom 170 received the study regimen: 86 received NNRTI-based ART, and 84 lopinavir–ritonavir–based ART. The incidence of malaria was lower among children receiving the lopinavir–ritonavir–based regimen than among those receiving the NNRTI-based regimen (1.32 vs. 2.25 episodes per person-year; incidence-rate ratio, 0.59; 95% confidence interval [CI], 0.36 to 0.97; P = 0.04), as was the risk of a recurrence of malaria after treatment with artemether–lumefantrine (28.1% vs. 54.2%; hazard ratio, 0.41; 95% CI, 0.22 to 0.76; P = 0.004). The median lumefantrine level on day 7 after treatment for malaria was significantly higher in the lopinavir–ritonavir group than in the NNRTI group. In the lopinavir–ritonavir group, lumefantrine levels exceeding 300 ng per milliliter on day 7 were associated with a reduction of more than 85% in the 63-day risk of recurrent malaria. A greater number of serious adverse events occurred in the lopinavir–ritonavir group than in the NNRTI group (5.6% vs. 2.3%, P = 0.16). Pruritus occurred significantly more frequently in the lopinavir–ritonavir group, and elevated alanine aminotransferase levels significantly more frequently in the NNRTI group. Conclusions Lopinavir–ritonavir–based ART as compared with NNRTI-based ART reduced the incidence of malaria by 41%, with the lower incidence attributable largely to a significant reduction in the recurrence of malaria after treatment with artemether–lumefantrine. Lopinavir–ritonavir–based ART was accompanied by an increase in serious adverse events. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT00978068.)

Tsetse flies Glossina spp. (Diptera: Glossinidae) harbor three different symbiotic microorganisms, one being an intracellular Rickettsia of the genus Wolbachia. This bacterium infects a wide range of arthropods, where it causes a variety of reproductive abnormalities, one of which is termed cytoplasmic incompatibility (CI) that, when expressed, results in embryonic death due to disruptions in fertilization events. We report here that in colonized flies, Wolbachia infections can be detected in 100% of sampled individuals, while infections vary significantly in field populations. Based on Wolbachia Surface Protein (wsp) gene sequence analysis, the infections associated with different fly species are all unique within the A group of the Wolbachia pipientis clade. In addition to being present in germ-line tissues, Wolbachia infections have been found in somatic tissues of several insects. Using a Wolbachia-specific PCR-based assay, the tissue tropism of infections in Glossina morsitans morsitans Westwood, Glossina brevipalpis Newstead and Glossina austeni Newstead were analysed. While infections in G. m. morsitans and G. brevipalpis were limited to reproductive tissues, in G. austeni, Wolbachia could be detected in various somatic tissues.

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Background Intermittent treatment with sulfadoxine-pyrimethamine, recommended for prevention of malaria in pregnant women throughout sub-Saharan Africa, is threatened by parasite resistance. We assessed the efficacy and safety of intermittent preventive treatment with dihydroartemisinin-piperaquine as an alternative to sulfadoxine-pyrimethamine. MethodsWe did a double-blind, randomised, controlled, superiority trial at one rural site in Uganda with high malaria transmission and sulfadoxine-pyrimethamine resistance. HIV-uninfected pregnant women between 12 and 20 weeks gestation were randomly assigned (1:1) to monthly intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine or dihydroartemisinin-piperaquine. The primary endpoint was the risk of a composite adverse birth outcome defined as low birthweight, preterm birth, or small for gestational age in livebirths. Protective efficacy was defined as 1-prevalence ratio or 1-incidence rate ratio. All analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02793622.

Objective We sought to measure retention in care and identify predictors of non-retention among patients receiving ART with streamlined delivery during the first year of the ongoing SEARCH “test-and-treat” trial (NCT 01864603) in rural Uganda and Kenya. Design Prospective cohort of patients in the intervention arm of the SEARCH Study. Methods We measured retention in care at 12 months among HIV-infected adults who linked to care and were offered ART regardless of CD4 cell count, following community-wide HIV-testing. Kaplan-Meier estimates and Cox proportional hazards modeling were used to calculate the probability of retention at one year and identify predictors of non-retention. Results Among 5,683 adults (age ≥ 15) who linked to care, 95.5% (95% CI: 92.9 – 98.1%) were retained in care at 12 months. The overall probability of retention at one year was 89.3% (95% CI: 87.6 – 90.7%) among patients newly linking to care and 96.4% (95% CI: 95.8 – 97.0%) among patients previously in care. Younger age and pre-ART CD4 below country treatment initiation guidelines were predictors of non-retention among all patients. Among those newly linking, taking more than 30 days to link to care after HIV diagnosis was additionally associated with non-retention at one year. HIV viral load suppression at 12 months was observed in 4,227/4736 (89%) of patients retained with valid viral load results. Conclusion High retention in care and viral suppression after 1 year were achieved in a streamlined HIV care delivery system in the context of a universal test-and-treat intervention.

In a malaria endemic area with a high level of molecular markers of antifolate resistance, the combined use of TMP/SMX prophylaxis and insecticide-treated bednets was associated with a dramatic reduction in malaria incidence among HIV-infected children.