Incidence of and socio-biologic risk factors for spontaneous preterm birth in HIV positive Nigerian women

BACKGROUND: Recent studies have identified HIV as a leading contributor to preterm delivery and its associated morbidity and mortality. However little or no information exists in our sub-region on this subject. Identifying the factors associated with preterm delivery in HIV positive women in our country and sub-region will not only prevent mother to child transmission of HIV virus but will also reduce the morbidity and mortality associated with prematurity and low birth weight. This study was designed to determine the incidence and risk factors for preterm delivery in HIV positive Nigerians. METHOD: The required data for this retrospective study was extracted from the data base of a cohort study of the outcome of prevention of mother to child transmission at the Nigerian Institute of Medical Research, Lagos. Only data of women that met the eligibility of spontaneous delivery after 20 weeks of gestation were included. Ethical approval was obtained from the Institution’s Ethical Review Board. RESULTS: 181 women out of the 1626 eligible for inclusion into the study had spontaneous preterm delivery (11.1%). The mean birth weight was 3.1 ± 0.4 kg, with 10.3% having LBW. Spontaneous preterm delivery was found to be significantly associated with unmarried status (cOR: 1.7;1.52-2.57), baseline CD4 count <200 cells/mm(3)(cOR: 1.8; 1.16-2.99), presence of opportunistic infection at delivery (cOR: 2.2;1.23-3.57), multiple pregnancy (cOR 10.4; 4.24 – 26.17), use of PI based triple ARV therapy (eOR 10.2; 5.52 – 18.8) in the first trimester (cOR 2.5; 1.77 – 3.52) on univariate analysis. However after multivariate analysis controlling for potential confounding variables including low birth weight, only multiple pregnancy (aOR: 8.6; CI: 6.73 – 12.9), presence of opportunistic infection at delivery (aOR: 1.9; CI: 1.1 – 5.7), and 1st trimester exposure to PI based triple therapy (aOR: 5.4; CI: 3.4 – 7.8) retained their significant association with preterm delivery. CONCLUSION: The spontaneous preterm delivery rate among our cohort was 11.1%. HIV positive women with multiple pregnancies, symptomatic HIV infection at delivery and first trimester fetal exposure to PI based triple therapy were found to be at risk of spontaneous preterm delivery. Early booking and non-use of PI based triple therapy in the first trimester will significantly reduce the risk of preterm delivery

Sero-prevalence and factors associated with Hepatitis B and C co-infection in pregnant Nigerian women living with HIV Infection

Introduction: Perinatal and horizontal transmission of Hepatitis B occur in areas of high endemicity as most infections are acquired in the first 5 years of life. Unless Hepatitis B and C infected pregnant women identified, and appropriate treatment provided, children born to these women are at high risk of chronic Hepatitis B (and C) virus infection. The objecive of this study was to determined the prevalence and the factors associated with Hepatitis B and C Virus infection in pregnant HIV positive Nigerians. Methods: A cross sectional study among HIV Positive pregnant women seen at a large PMTCT clinic in  Lagos Nigeria. The women were screened for Hepatitis B and C Virus infection at enrollment. HIV viral  load, CD4 count, liver transaminases and hemoglobin levels were also determined. Data were managed  with SPSS for windows version. Ethical approval was obtained from the Institution?s Ethical Review  Board. Results: Of the 2391 studied subjects, 101(4.2%) and 37(1.5%) respectively were seropositive for  Hepatitis B and C Virus infection. Twowomen (0. 08%) had triple infections. blood transfusion, (cOR: 2.3; 95% CI:1.1 - 4.6), history of induced abortion (cOR:2. 2;95% CI:1.3 - 3.6), and elevated baseline ALT (cOR:2. 2; 95%CI:2. 2;4.2) were significantly associated with HBV. History of induced abortion was the only factor found to be associated with HIV/ HCV (cOR: 1.9;95%CI:1. 3-3.9). Conclusion: Hepatitis B Virus infection (4.2%) is relatively common in our environment and associated  with induced abortion, blood transfusion and elevated baseline transaminase. Hepatitis C Virus infection (1.5%) is less common and associated with only history of induced abortion. Key words: Hepatitis B virus, Hepatitis C virus, HIV, pregnanc

Exposure of Allium cepa root cells to zidovudine or nevirapine induces cytogenotoxic changes.

Antiretroviral drugs have proved useful in the clinical management of HIV-infected persons, though there are concerns about the effects of exposure to these DNA-reactive drugs. We investigated the potential of the plant model Allium cepa root tip assay to demonstrate the cytogenotoxicity of zidovudine and nevirapine and as a replace-reduce-refine programme amenable to resource-poor research settings. Cells mitotic index were determined in squashed root cells from Allium cepa bulbs exposed to zidovudine or nevirapine for 48 hr. The concentration of zidovudine and nevirapine inhibiting 50% root growth after 96 hr exposure was 65.0 µM and 92.5 µM respectively. Root length of all antiretroviral-exposed roots after 96 hr exposure was significantly shorter than the unexposed roots while additional root growth during a subsequent 48 hr recovery period in the absence of drug was not significantly different. By ANOVA, there was a significant association between percentage of cells in mitosis and zidovudine dose (p=0.004), but not nevirapine dose (p=0.68). Chromosomal aberrations such as sticky chromosomes, chromatin bridges, multipolar mitoses and binucleated cells were observed in root cells exposed to zidovudine and nevirapine for 48 hr. The most notable chromosomal aberration was drug-related increases in sticky chromosomes. Overall, the study showed inhibition in root length growth, changes in the mitotic index, and the induction of chromosomal aberrations in Allium bulbs treated for 96 hr or 48 hr with zidovudine and nevirapine. The study reveals generalized cytogenotoxic damage induced by exposure to zidovudine and nevirapine, and further show that the two compounds differ in their effects on mitosis and the types of chromosomal aberrations induced

Enzyme Responsive Vaginal Microbicide Gels Containing Maraviroc and Tenofovir Microspheres Designed for Acid Phosphatase-Triggered Release for Pre-Exposure Prophylaxis of HIV-1: A Comparative Analysis of a Bigel and Thermosensitive Gel

The challenges encountered with conventional microbicide gels has necessitated the quest for alternative options. This study aimed to formulate and evaluate a bigel and thermosensitive gel, designed to combat the challenges of leakage and short-residence time in the vagina. Ionic-gelation technique was used to formulate maraviroc and tenofovir microspheres. The microspheres were incorporated into a thermosensitive gel and bigel, then evaluated. Enzyme degradation assay was used to assess the effect of the acid phosphatase enzyme on the release profile of maraviroc and tenofovir microspheres. HIV efficacy and cytotoxicity of the microspheres were assessed using HIV-1-BaL virus strain and HeLa cell lines, respectively. Maraviroc and tenofovir release kinetics followed zero-order and Higuchi model kinetics. However, under the influence of the enzyme, maraviroc release was governed by first-order model, while tenofovir followed a super case II transport-mechanism. The altered mode of release and drug transport mechanism suggests a triggered release. The assay of the microspheres suspension on the HeLa cells did not show signs of cytotoxicity. The thermosensitive gel and bigel elicited a progressive decline in HIV infectivity, until at concentrations of 1 &mu;g/mL and 0.1 &mu;g/mL, respectively. The candidate vaginal gels have the potential for a triggered release by the acid phosphatase enzyme present in the seminal fluid, thus, serving as a strategic point to prevent HIV transmission

Micrographs of chromosomal aberrations seen in the treatment groups.

<p>A – Normal metaphase from the negative control group. *B – Vagrant metaphase form with misaligned chromosomes in cell from 32.5 µM ZDV. *C – C-Metaphase chromosomes seen only in cells exposed to 32.5 µM ZDV. D – Cell exposed to 65 µM ZDV showing sticky chromosomes. E – Normal anaphase (early) from the negative control group. F – Mitotic figure from cell exposed to 6.5 µM ZDV showing anaphase bridges (arrowed). G – Mitotic figure showing cell exposed to 6.5 µM ZDV; arrows indicate uneven breaks (black) and chromosomal fragment (patterned). H – Interphase cells exposed to 6.5 µM ZDV indicating interphase arrest. *Challenges with instruments delayed taking micrographs till some slides started drying.</p

Root length during the 96(horizontal stripes) and 144 hr (vertical stripes) growth periods.

<p>For 96(NC  =  negative control), ZDV or NVP. From 96 hr to 144 hr (vertical stripes), all bulbs were grown in water without drug. Root length (mm) shown is mean ± Standard error, with n = 5 bulbs per group.</p

Percentage of <i>Allium</i> cells with various chromosomal aberrations after exposure for 48 hr to ZDV or NVP.

a<p><i>Sticky chromosomes</i> refer to the tendency of chromosome arms or entire chromosomes to stick together.</p>b<p><i>Chromatin bridges</i> occur in mitosis when the telomeres of sister chromatids fuse together and fail to completely segregate into their respective daughter cells. ^c<i>Vagrant forms</i> refer to chromosomal formations different from the normal formation during mitosis.</p>d<p><i>Binucleated cells</i> have more than one nucleus. ^e<i>Multipolar mitosis</i> occurs when the chromosomal material is pulled to more than two poles, resulting in the formation of a corresponding number of nuclei. ^f<i>Chromosomal fragments</i> refer to fragments of a chromosome that may be lacking a centromere and so is often lost when the cell divide.</p

<i>Allium cepa</i> root length grown for 96 hr in zidovudine (black line) or nevirapine (grey line).

<p>Expressed as percentage of the unexposed control with value 34.6±2.7 mm (mean ± SE; n = 5 bulbs/group). The drug concentration giving half maximal root growth length (EC₅₀) for zidovudine (ZDV) was 65.0 µM, and for nevirapine (NVP) was 92.5 µM. At the 400, 800 and 1200 µM doses, roots from the NVP-exposed groups were significantly longer than those from the ZDV-exposed groups.</p

Impact of ZDV and NVP on the mitotic index of <i>Allium cepa</i> root cells^a exposed for 48 hr.

a<p>Each experimental group contained 10 bulbs and 2–3 root tips from each bulb were squashed together on one slide. On each slide 40–100 cells were examined. Values shown are means ± standard deviation of the mean.</p>b<p>EC₅₀ is the concentration of drug that inhibits <i>Allium</i> root growth length by 50%; 10% of EC₅₀ is 5% of total root growth length.</p>c<p>For the percentage of cells in mitosis: for unexposed vs.32.5 µM ZDV, <i>p</i> = 0.02; for ZDV 50% of EC₅₀ vs. NVP 50% of EC₅₀, <i>p</i> = 0.03. All other associations were statistically non-significant.</p