Vaginal microbiome community state types and high-risk human papillomaviruses in cervical precancer and cancer in North-central Nigeria.

BACKGROUND: High risk human papillomaviruses (HR-HPV) have a causal role in cervical oncogenesis, and HIV-mediated immune suppression allows HR-HPV to persist. We studied whether vaginal microbiome community state types (CSTs) are associated with high-grade precancer and/or invasive cervical cancer (HSIL/ICC). METHODS: This was a cross-sectional study of adult women with cervical cancer screening (CCS) at the Jos University Teaching Hospital (JUTH) in Jos, Nigeria, between January 2020 and February 2022. Cervical swabs underwent HPV genotyping (Anyplex™ II HPV28). Cervico-vaginal lavage (CVL) sample was collected for 16 S rRNA gene amplicon sequencing. We used multivariable logistic regression modelling to assess associations between CSTs and other factors associated with HSIL/ICC. RESULTS: We enrolled 155 eligible participants, 151 with microbiome data for this analysis. Women were median age 52 (IQR:43-58), 47.7% HIV positive, and 58.1% with HSIL/ICC. Of the 138 with HPV data, 40.6% were negative for HPV, 10.1% had low-risk HPV, 26.8% had single HR-HPV, and 22.5% had multiple HR-HPV types. The overall prevalence of any HR-HPV type (single and multiple) was 49.3%, with a higher proportion in women with HSIL/ICC (NILM 31.6%, LSIL 46.5%, HSIL 40.8%, and 81.5% ICC; p = 0.007). Women with HIV were more likely to have HSIL/ICC (70.3% vs. 29.7% among women without HIV). In crude and multivariable analysis CST was not associated with cervical pathology (CST-III aOR = 1.13, CST-IV aOR = 1.31). However, in the presence of HR-HPV CST-III (aOR = 6.7) and CST-IV (aOR = 3.6) showed positive association with HSIL/ICC. CONCLUSION: Vaginal microbiome CSTs were not significantly associated with HSIL/ICC. Our findings suggest however, that CST could be helpful in identifying women with HSIL/ICC and particularly those with HR-HPV. Characterization of CSTs using point-of-care molecular testing in women with HR-HPV should be studied as an approach to improve early detection and cervical cancer prevention. Future longitudinal research will improve our understanding of the temporal effect of non-optimal CST, HR-HPV, and other factors in cervical cancer development, prevention, and control.

Pregnancy Desirability and Motivational Readiness for Postpartum Contraceptive Use: Findings from Population-Based Surveys in Eight Sub-Saharan African Countries.

This study examined the associations between pregnancy intention and motivational readiness for postpartum contraceptive use. Data for this cross-sectional analysis were derived from nationally representative surveys of the Performance Monitoring and Accountability 2020 (PMA2020) project conducted in eight sub-Saharan African countries. Participants included 9488 nonpregnant women of reproductive age (15-49 years) who had given birth in the last 2 years. Weighted multinomial logistic regression analyses were performed to estimate the odds ratios (OR) and their corresponding 95% confidence intervals (CIs) of the associations of motivational readiness for contraceptive adoption categorized as precontemplation, contemplation, and post-action with pregnancy intention. After adjusting for confounding factors, the findings revealed that women in Côte d'Ivoire and Nigeria who had mistimed pregnancies had significantly higher odds of being in the contemplation vs. precontemplation stage compared to those who had intended pregnancies. Similarly, women who had unwanted pregnancies in Ethiopia were also more likely to be in the contemplation stage. Furthermore, significant differences were observed for women in Burkina Faso, Côte d'Ivoire, and Nigeria regarding the association between mistimed pregnancies and being in the post-action stage. For women who had unwanted pregnancies, this association was significant only in Nigeria. Additionally, the odds of being in the contemplation stage, compared to the post-action stage, for women who had unwanted pregnancies were significantly higher in Ethiopia and Nigeria. These results indicate that recent unintended pregnancies in specific sub-Saharan African countries may motivate women to take action to prevent future unintended pregnancies. The findings underscore the importance of tailored and context-specific approaches in family-planning programs based on the stage of motivational readiness.

Implication of First-Line Antiretroviral Therapy Choice on Second-Line Options.

BACKGROUND: Although there are a number of studies comparing the currently recommended preferred and alternative first-line (1L) antiretroviral therapy (ART) regimens on clinical outcomes, there are limited data examining the impact of 1L regimen choice and duration of virologic failure (VF) on accumulation of drug resistance mutations (DRM). The patterns of DRM from patients failing zidovudine (AZT)-containing versus tenofovir (TDF)-containing ART were assessed to evaluate the predicted susceptibility to second-line (2L) nucleoside reverse-transcriptase inhibitor (NRTI) backbone options in the context of an ongoing programmatic setting that uses viral load (VL) monitoring. METHODS: Paired samples from Nigerian ART patients who experienced VF and switched to 2L ART were retrospectively identified. For each sample, the human immunodeficiency virus (HIV)-1 polymerase gene was sequenced at 2 time points, and DRM was analyzed using Stanford University's HIVdb program. RESULTS: Sequences were generated for 191 patients. At time of 2L switch, 28.2% of patients on AZT-containing regimens developed resistance to TDF, whereas only 6.8% of patients on TDF-containing 1L had mutations compromising susceptibility to AZT. In a stratified evaluation, patients with 0-6 months between tested VL samples had no difference in proportion compromised to 2L, whereas those with >6 months between samples had a statistically significant difference in proportion with compromised 2L NRTI. In multivariate analyses, patients on 1L AZT had 9.90 times higher odds of having a compromised 2L NRTI option than patients on 1L TDF. CONCLUSIONS: In the context of constrained resources, where VL monitoring is limited, we present further evidence to support use of TDF as the preferred 1L NRTI because it allows for preservation of the recommended 2L NRTI option.

Foetal loss and enhanced fertility observed in mice treated with Zidovudine or Nevirapine.

BACKGROUND: Health concerns for HIV-infected persons on antiretroviral therapy (ART) have moved from morbidity to the challenges of long-term ART. We investigated the effect of Zidovudine or Nevirapine on reproductive capacity across two mouse generations. METHODS: A prospective mouse study with drugs administered through one spermatogenic cycle. Mouse groups (16 males and 10 females) were given Zidovudine or Nevirapine for 56 days. Males were mated to untreated virgin females to determine dominant lethal effects. Twenty females (10 treated and 10 untreated) mated with the treated males per dose and gave birth to the F1 generation. Parental mice were withdrawn from drugs for one spermatogenic cycle and mated to the same dams to ascertain if effects are reversible. The F1 generation were exposed for another 56 days and mated to produce the F2 generation. RESULTS: Foetal loss was indicated in the dominant lethal assay as early as four weeks into drug administration to the males. At the first mating of the parental generation to produce the F1 generation, births from 10 dams/dose when the 'father-only' was exposed to Zidovudine (10, 100 and 250 mg/kg) was 3, 2 and 1 while it was 7, 1 and 4 respectively when 'both-parents' were exposed. Similarly births from the parental generation first mating when the 'father-only' was exposed to Nevirapine (5, 50 and 150 mg/kg) was 2, 2 and 0 while it was 6, 5 and 9 respectively when 'both-parents' were exposed. However, fertility was not significantly different neither by dose nor by the parental exposure. The F1 mice mated to produce the F2 generation recorded only one birth. CONCLUSION: The dominant lethal analysis showed foetal loss occurred when the "fathers-only" were treated while fertility was enhanced when "both-parents" were on therapy at the time of mating.

Prevalence and risk factors of asymptomatic bacteriuria among pregnant Nigerians infected with HIV.

OBJECTIVE: There are conflicting report on the association of HIV infection and asymptomatic bacteriuria (ASB). Most of these studies were from areas with low HIV burden. This study determined the prevalence and risk factors of ASB in HIV positive pregnant women. METHODS: A cross sectional study among HIV positive pregnant women seen at a large PMTCT clinic in Lagos Nigeria. The women were evaluated for ASB at first clinic attendance. Blood samples were also collected for viral load, CD4 count and hemoglobin levels assessment. Data were managed with SPSS for windows version 19. RESULTS: 102 (18.1%) women out of 563 studied were found positive for asymptomatic bacteriuria. Ninety-seven (95.1%) of the positive samples yielded single bacterial isolates. Escherichia coli (44.3%) and Proteus mirabilis (21.6%) were the most common bacterial isolates. Previous urinary tract infection (OR: 4.3), HIV-1 RNA greater than 10,000 copies/ml (OR: 3.9), CD4 count <200 cells/mm3 (OR: 1.4) and maternal hemoglobin <11 g/dl (OR: 1.4) were factors significantly associated with ASB after controlling for possible confounders. CONCLUSION: ASB is common in HIV positive pregnant women in our environment and is associated with previous UTI, high viral load, low CD4 count and maternal hemoglobin <11 g/dl.

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.

Assessment of the vitamin B12 status of pregnant women in Nigeria using plasma holotranscobalamin.

Maternal vitamin B12 deficiency during pregnancy is an independent risk factor for neural tube defects and other neurological problems in infants. We determined the vitamin B12 status of 143 pregnant women in Nigeria representing all trimesters who presented to an antenatal clinic in Jos, Nigeria, using holotranscobalamin II levels (holoTCII), which is a measure of the vitamin B12 that is available for uptake into tissues. The holoTCII concentration ranged from 13 to 128 pmol/L. Using a cutoff of 40 pmol/L, 36% of the women were classified as vitamin B12-deficient. HoloTCII concentrations correlated negatively with plasma homocysteine levels (r = -0.24, P = 0.003) and positively with red blood cell folate concentrations (r = 0.28, P < 0.001). These data underscore the importance of supplementing pregnant women in Nigeria with vitamin B12 in order to ensure adequate vitamin B12 status and decrease the risk for neural tube defects.