Cotrimoxazole Prophylaxis and Risk of Severe Anemia or Severe Neutropenia in HAART-Exposed, HIV-Uninfected Infants

Background: Prophylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia. Methods: We compared the proportion of HIV-exposed uninfected (HIV-EU) infants experiencing incident severe anemia (and separately, severe neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole from 1 to 6 months vs. infants from two prior trials who did not receive cotrimoxazole. Infants were from rural and urban communities in southern Botswana. Results: A total of 1705 HIV-EU infants were included. Among these 645 (37.8%) were fed with iron-supplemented formula from birth. Severe anemia developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In an analysis stratified by infant feeding method, there were no significant differences in the risk of severe anemia by prophylactic cotrimoxazole exposure–risk difference, −0.69% (95% confidence interval [CI] −2.1 to 0.76%). Findings were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI 0.07 to 1.65). There were also no significant differences observed for severe neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI −1.3 to 5.2%) and aOR 0.80 (95% CI 0.33 to 1.93). Conclusions: Severe anemia and severe neutropenia were infrequent among HIV-exposed uninfected infants receiving cotrimoxazole from 1–6 months of age. Concerns regarding hematologic toxicity should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected infants. ClinicalTrials.gov Registration Numbers NCT01086878 (http://clinicaltrials.gov/show/NCT01086878), NCT00197587 (http://clinicaltrials.gov/show/NCT00197587), and NCT00270296 (http://clinicaltrials.gov/show/NCT00270296)

Birth Weight for Gestational Age Norms for a Large Cohort of Infants Born to HIV-Negative Women in Botswana Compared with Norms for U.S.-Born Black Infants

Background: Standard values for birth weight by gestational age are not available for sub-Saharan Africa, but are needed to evaluate incidence and risk factors for intrauterine growth retardation in settings where HIV, antiretrovirals, and other in utero exposures may impact birth outcomes. Methods: Birth weight data were collected from six hospitals in Botswana. Infants born to HIV-negative women between 26-44 weeks gestation were analyzed to construct birth weight for gestational age charts. These data were compared with published norms for black infants in the United States. Results: During a 29 month period from 2007-2010, birth records were reviewed in real-time from 6 hospitals and clinics in Botswana. Of these, 11,753 live infants born to HIV-negative women were included in the analysis. The median gestational age at birth was 39 weeks (1st quartile 38, 3rd quartile 40 weeks), and the median birth weight was 3100 grams (1st quartile 2800, 3rd quartile 3400 grams). We constructed estimated percentile curves for birth weight by gestational age which demonstrate increasing slope during the third trimester and leveling off beyond 40 weeks. Compared with black infants in the United States, Botswana-born infants had lower median birth weight for gestational age from weeks 37 through 42 (p < .02). Conclusions: We present birth weight for gestational age norms for Botswana, which are lower at term than norms for black infants in the United States. These findings suggest the importance of regional birth weight norms to identify and define risk factors for higher risk births. These data serve as a reference for Botswana, may apply to southern Africa, and may help to identify infants at risk for perinatal complications and inform comparisons among infants exposed to HIV and antiretrovirals in utero

High Prevalence of Hypertension and Placental Insufficiency, but No In Utero HIV Transmission, among Women on HAART with Stillbirths in Botswana

Background: Increased stillbirth rates occur among HIV-infected women, but no studies have evaluated the pathological basis for this increase, or whether highly active antiretroviral therapy (HAART) influences the etiology of stillbirths. It is also unknown whether HIV infection of the fetus is associated with stillbirth. Methods: HIV-infected women and a comparator group of HIV-uninfected women who delivered stillbirths were enrolled at the largest referral hospital in Botswana between January and November 2010. Obstetrical records, including antiretroviral use in pregnancy, were extracted at enrollment. Verbal autopsies; maternal HIV, CD4 and HIV RNA testing; stillbirth HIV PCR testing; and placental pathology (blinded to HIV and treatment status) were performed. Results: Ninety-nine stillbirths were evaluated, including 62 from HIV-infected women (34% on HAART from conception, 8% on HAART started in pregnancy, 23% on zidovudine started in pregnancy, and 35% on no antiretrovirals) and 37 from a comparator group of HIV-uninfected women. Only 2 (3.7%) of 53 tested stillbirths from HIV-infected women were HIV PCR positive, and both were born to women not receiving HAART. Placental insufficiency associated with hypertension accounted for most stillbirths. Placental findings consistent with chronic hypertension were common among HIV-infected women who received HAART and among HIV-uninfected women (65% vs. 54%, p = 0.37), but less common among HIV-infected women not receiving HAART (28%, p = 0.003 vs. women on HAART). Conclusions: In utero HIV infection was rarely associated with stillbirths, and did not occur among women receiving HAART. Hypertension and placental insufficiency were associated with most stillbirths in this tertiary care setting

Co-Operative Additive Effects between HLA Alleles in Control of HIV-1

Background: HLA class I genotype is a major determinant of the outcome of HIV infection, and the impact of certain alleles on HIV disease outcome is well studied. Recent studies have demonstrated that certain HLA class I alleles that are in linkage disequilibrium, such as HLA-A*74 and HLA-B*57, appear to function co-operatively to result in greater immune control of HIV than mediated by either single allele alone. We here investigate the extent to which HLA alleles - irrespective of linkage disequilibrium - function co-operatively. Methodology/Principal Findings: We here refined a computational approach to the analysis of >2000 subjects infected with C-clade HIV first to discern the individual effect of each allele on disease control, and second to identify pairs of alleles that mediate ‘co-operative additive’ effects, either to improve disease suppression or to contribute to immunological failure. We identified six pairs of HLA class I alleles that have a co-operative additive effect in mediating HIV disease control and four hazardous pairs of alleles that, occurring together, are predictive of worse disease outcomes (q<0.05 in each case). We developed a novel ‘sharing score’ to quantify the breadth of CD8+ T cell responses made by pairs of HLA alleles across the HIV proteome, and used this to demonstrate that successful viraemic suppression correlates with breadth of unique CD8+ T cell responses (p = 0.03). Conclusions/Significance: These results identify co-operative effects between HLA Class I alleles in the control of HIV-1 in an extended Southern African cohort, and underline complementarity and breadth of the CD8+ T cell targeting as one potential mechanism for this effect

Determination of masses of the central black holes in NGC524 and NGC2549 using Laser Guide Star Adaptive Optics

[abridged] We present observations of NGC524 and NGC2549 with LGS AO obtained at GEMINI North telescope using the NIFS IFU in the K band. The purpose of these observations, together with previously obtained observations with the SAURON IFU, is to determine the masses (Mbh) of the supermassive black holes (SMBH). The targeted galaxies were chosen to have central light profiles showing a core (NGC524) and a cusp (NGC2549), to probe the feasibility of using the galaxy centre as the NGS required for LGS AO. We employ an innovative `open loop' technique. The data have spatial resolution of 0.23" and 0.17" FWHM, showing that high quality LGS AO observations of these objects are possible. We construct axisymmetric three-integral dynamical models which are constrained with both the NIFS and SAURON data. The best fitting models yield Mbh=(8.3 +2.7 -1.3) x 10^8 Msun for NGC524 and Mbh=(1.4 +0.2 -1.3) x 10^7 Msun for NGC2549 (all errors are at the 3 sigma CL). We demonstrate that the wide-field SAURON data play a crucial role in the M/L determination increasing the accuracy of M/L by a factor of at least 5, and constraining the upper limits on Mbh. The NIFS data are crucial in constraining the lower limits of Mbh and in combination with the large scale data reducing the uncertainty by a factor of 2 or more. We find that the orbital structure of NGC524 shows significant tangential anisotropy, while at larger radii both galaxies are consistent with having almost perfectly oblate velocity ellipsoids. Tangential anisotropy in NGC524 coincides with the size of SMBH sphere of influence and the core region in the light profile. We test the accuracy to which Mbh can be measured using seeings obtained from typical LGS AO observations, and conclude that for a typical conditions and Mbh the expected uncertainty is of the order of 50%.Comment: 19 pages, 14 figure

The ATLAS3D project - XXVII : Cold gas and the colours and ages of early-type galaxies

Date of Acceptance: 16/12/2013We present a study of the cold gas contents of the ATLAS3D early-type galaxies, in the context of their optical colours, near-ultraviolet colours and Hβ absorption line strengths. Early-type (elliptical and lenticular) galaxies are not as gas poor as previously thought, and at least 40 per cent of local early-type galaxies are now known to contain molecular and/or atomic gas. This cold gas offers the opportunity to study recent galaxy evolution through the processes of cold gas acquisition, consumption (star formation) and removal. Molecular and atomic gas detection rates range from 10 to 34 per cent in red sequence early-type galaxies, depending on how the red sequence is defined, and from 50 to 70 per cent in blue early-type galaxies. Notably, massive red sequence early-type galaxies (stellar masses >5 × 1010 M⊙, derived from dynamical models) are found to have H I masses up to M(H I)/M* ∼ 0.06 and H2 masses up to M(H2)/M* ∼ 0.01. Some 20 per cent of all massive early-type galaxies may have retained atomic and/or molecular gas through their transition to the red sequence. However, kinematic and metallicity signatures of external gas accretion (either from satellite galaxies or the intergalactic medium) are also common, particularly at stellar masses ≤5 × 1010 M⊙, where such signatures are found in ∼50 per cent of H2-rich early-type galaxies. Our data are thus consistent with a scenario in which fast rotator early-type galaxies are quenched former spiral galaxies which have undergone some bulge growth processes, and in addition, some of them also experience cold gas accretion which can initiate a period of modest star formation activity. We discuss implications for the interpretation of colour–magnitude diagramsPeer reviewedFinal Accepted Versio