Human Immunodeficiency Virus In Zambia Research Articles

Brain Imaging in New-Onset Seizure of Children Living With Human Immunodeficiency Virus in Zambia

BackgroundThere are an estimated 1.5 million children living with human immunodeficiency virus (CLHIV), most residing in sub-Saharan Africa. A common hospital presentation of CLHIV is new-onset seizure, for which imaging is helpful but not routinely performed due to scarce resources. We present imaging findings and their association with clinical risk factors and outcomes in a cohort of Zambian CLHIV presenting with new-onset seizure. MethodsIn this prospective cohort study, participants were recruited at the University Teaching Hospital in Lusaka, Zambia. Various clinical and demographic characteristics were obtained. Computed tomography (CT), magnetic resonance imaging (MRI), or both were obtained during admission or shortly after discharge. If both studies were available, MRI data was used. Two neuroradiologists interpreted images using REDCap-based NeuroInterp, a tool that quantifies brain imaging findings. Age-dependent neuropsychologic assessments were administered. ResultsNineteen of 39 (49%) children had a brain MRI, 16 of 39 (41%) had CT, and four of 39 (10%) had both. Mean age was 6.8 years (S.D. = 4.8). Children with advanced HIV disease had higher odds of atrophy (odds ration [OR] 7.2, 95% confidence interval [CI] 1.1 to 48.3). Focal abnormalities were less likely in children receiving antiretroviral therapy (ART) (OR 0.22, 95% CI 0.05 to 1.0). Children with neurocognitive impairment were more likely to have atrophy (OR 8.4, 95% CI 1.3 to 55.4) and less likely to have focal abnormalities (OR 0.2, 95% CI 0.03 to 0.9). ConclusionsFocal brain abnormalities on MRI were less likely in CLHIV on ART. Brain atrophy was the most common imaging abnormality, which was linked to severe neurocognitive impairment.

Factors associated with fertility intentions among women living with and without human immunodeficiency virus in Zambia.

Zambia is one of the countries in sub-Saharan Africa with a high prevalence of human immunodeficiency virus among women of reproductive age. Notably, the literature shows that human immunodeficiency virus status is one of the factors that influence fertility intention among women of reproductive age. With increased access, uptake and coverage of anti retroviral therapy, there is a need to understand the influence of human immunodeficiency virus status on fertility intentions of women of reproductive age in Zambia. The purpose of this study was to determine the fertility intentions of both mothers living with human immunodeficiency virus and mothers living without human immunodeficiency virus in Zambia. This study adopted a cross-sectional design using data collected by the Zambia Demographic and Health Survey conducted in 2018. The study sample comprised 7983 mothers in the reproductive age (15-49 years), of which 6704 were mothers living without human immunodeficiency virus and 1279 were mothers living with human immunodeficiency virus. Here, we determined the fertility intentions of mothers living with human immunodeficiency virus and mothers living without human immunodeficiency virus using secondary data. Multivariable logistic regression models were used to determine the association of individual and household socio-demographic factors on fertility intentions of mothers living with human immunodeficiency virus and mothers living without human immunodeficiency virus in Zambia. Fertility intention among mothers living with human immunodeficiency virus was 42.1% while that on mothers living without human immunodeficiency virus was 55.5%. Regardless of human immunodeficiency virus status, fertility intention reduced with increasing age. Mothers aged 35-49 years who were living with human immunodeficiency virus (adjusted odds ratio = 0.12, 95% confidence interval = 0.06-0.24) and mothers aged 35-49 years who were living without human immunodeficiency virus (adjusted odds ratio = 0.18, 95% confidence interval = 0.13-0.26) had lower odds of intention to have another child compared to mothers aged 15-24 years. Furthermore, married mothers living with human immunodeficiency virus and those living without human immunodeficiency virus had increased odds of intention of having another child (adjusted odds ratio = 2.52, 95% confidence interval = 1.36-4.66) and (adjusted odds ratio = 3.21, 95% confidence interval = 2.36-4.36), respectively. The study has established that age, marital status, parity and employment status were associated with fertility intention among women living with and without human immunodeficiency virus. The results necessitate the need for enhanced maternal health education for mothers regardless of human immunodeficiency virus status. Furthermore, there is a need for continuous counselling for both women living with human immunodeficiency virus and without human immunodeficiency virus during their routine human immunodeficiency virus care, to improve and enhance pregnancy outcomes.

High-risk human papillomavirus-associated vulvar neoplasia among women living with human immunodeficiency virus in Zambia.

BackgroundGlobally, women living with HIV have a higher risk of vulvar neoplasia than HIV-negative women. Vulvar neoplasia among women living with HIV has not previously been characterised in Zambia.ObjectiveThis study determined the clinical and pathologic features of vulvar neoplasia among women living with HIV at the University Teaching Hospital, Lusaka, Zambia.MethodsWe conducted a cross-sectional study of vulvar lesions among 53 women living with HIV who presented with vulvar lesions between July 2017 and February 2018. The study assessed clinical and histological characteristics and prevalence of high-risk human papillomavirus (HRHPV).ResultsTwenty-one patients were diagnosed with vulvar squamous cell carcinoma (VSCC), 20 with usual vulvar intraepithelial neoplasm (uVIN), and the rest with either benign lesions or non-neoplastic lesions (NNL). Participants’ mean age was 40 years. Patients with VSCC were significantly older than those with NNL (mean (s.d.): 43 (21) vs 33 (10), p = 0.004). The prevalence of HRHPV was 88.9% in VSCC patients and 100.0% in high-grade squamous intraepithelial lesion patients. HPV16 was the most common (52.6%) genotype. The clinical features of neoplasia were similar to those of NNL.ConclusionVSCC was significantly more common among women aged ≥ 40 years. HRHPV in VSCC and high-grade squamous intraepithelial lesions was high. Women with vulvar lesions, especially those aged > 40 years, should be evaluated for vulvar cancer. Young girls should be vaccinated to prevent vulvar cancer.

Randomized control trial of thermal ablation of the cervix in women living with the human immunodeficiency virus in Zambia

<h3>Objectives:</h3> A randomized control trial of a battery-operated thermocoagulator for the treatment of precancerous cervical lesions is ongoing in Lusaka, Zambia. We describe preliminary results of treatment efficacy in HIV-positive women. <h3>Methods:</h3> Visual inspection with acetic acid (VIA) screen-positive women eligible for ablative treatment are randomized to receive thermal ablation (TA), cryotherapy or large loop excision of the transformation zone (LLETZ). Demographic information is collected, including human immunodeficiency virus (HIV) status and antiretroviral therapy (ART) use. Human papillomavirus (HPV) DNA sampling for known or suspected oncogenic HPV types is performed at baseline and follow-up. Treatment efficacy is based on VIA and HPV status at 6- and/or 12-month follow-up. Side-effects, pain and client satisfaction are scored and recorded, however, these data are not included in this analysis. <h3>Results:</h3> Of the 1,683 women who have been randomized to treatment, 994 (59%) are HIV-positive with the vast majority (97%) on anti-retroviral therapy (ART). HIV-positive women were equally distributed between treatment arms (p=0.28). Among the 1328 (79%) eligible for follow-up, follow-up data are available on 722 women (54%), of which 383 are HIV-positive. Based on VIA results alone for cure, HIV positive women had lower overall cure rates than HIV-negative women (77% vs 88%, respectively, p<0.001), regardless of treatment type. HIV-positive women, who were also positive for HPV 16 at baseline, had significantly lower cure rates (HPV 16 clearance and VIA negative) across all study arms, compared to HIV-negative women (73% vs 88%, respectively, p<0.001). When all HPV types are considered, overall cure rates (clearance of baseline type-specific HPV and VIA negative) in HIV positive women decreased to 49% and did not differ based on duration of HIV infection (<2 years, 43%; >2yrs, 55%; p=0.072). <h3>Conclusions:</h3> In May 2020, the 173^rd World Health Assembly adopted the Global Strategy to Eliminate Cervical Cancer. This sub-analysis of data from a randomized control trial of locally ablative methods for cervical precancer highlights the challenges in eradicating this disease in women living with HIV. Investigations are underway to determine the underlying causes of these findings. (NCI Grant No. 4UH3CA202721-03)

Assessment of the tuberculosis case-finding and prevention cascade among people living with HIV in Zambia \u2013 2018: a cross-sectional cluster survey

BackgroundThe Ministry of Health Zambia recommends tuberculosis preventive treatment (TPT) with 6 months daily isoniazid for all people living with human immunodeficiency virus (HIV) after ruling out active tuberculosis disease. We sought to estimate the percentage of people living with HIV who progress through each stage of the tuberculosis case-finding and prevention cascade in two provinces with the highest tuberculosis burden in Zambia.MethodsIn this cross-sectional survey, we used a two-stage cluster sampling method. We sampled 12 healthcare facilities with probability proportional to size. Patient volume determined facility cluster size. During October 2018, from each facility we systematically sampled medical records of adults and children living with HIV. Our primary outcome of interest was TPT initiation rate among eligible people living with HIV, weighted for complex survey design. The Rao-Scott adjusted chi-square test was used to test for differences in TPT initiation rate and other indicators from the tuberculosis prevention cascade by age group and province of residence. Additionally, we conducted semi-structured interviews with healthcare workers at each facility to assess TPT knowledge and identify challenges to its implementation.ResultsWe sampled 482 records of people living with HIV (including 128 children living with HIV). Excluding two people diagnosed with tuberculosis disease before enrollment in HIV care, 93.4% underwent tuberculosis symptom screening. Of those, 4.7% were diagnosed with tuberculosis disease and 95.3% were TPT-eligible, of whom 24.7% initiated TPT. TPT initiation was lower among eligible children (7.7%) compared with adults (25.2%, p = 0.03) and Copperbelt residents (3.1%) compared with Lusaka residents (35.8%, p < 0.01). TPT completion rate was 38.4% among people living with HIV who initiated the 6-month course. Among interviewed healthcare workers, 58.3% (unweighted) incorrectly relayed the number of symptoms needed for a positive tuberculosis symptom screen, 83.3% (unweighted) reported insufficient isoniazid stockpile for completion at the time of TPT initiation, and only 27.3% (unweighted) reported receiving TPT-specific training.ConclusionsTPT uptake among people living with HIV in Zambia is challenged by inconsistent tuberculosis screening, lack of TPT training for healthcare workers, and supply chain inefficiencies. Addressing these barriers may increase TPT initiations and improve outcomes among people living with HIV.

Evaluating the impact of antiretroviral and antiseizure medication interactions on treatment effectiveness among outpatient clinic attendees with HIV in Zambia.

Interactions between enzyme-inducing anti-seizure medications (EI-ASMs) and antiretroviral drugs (ARVs) can lead to decreased ARV levels and may increase the likelihood of viral resistance. We conducted a study to determine if co-usage of ARVs and EI-ASMs is associated with ARV-resistant human immunodeficiency virus (HIV) among people living with HIV in Zambia. Eligible participants were ≥18years of age and concurrently taking ASMs and ARVs for at least 1month of the prior 6-month period. Data were obtained regarding medication and HIV history. CD4 counts, plasma viral loads (pVLs), and HIV genotype and resistance profile in participants with a pVL >1000copies/mL were obtained. Pearson's test of independence was used to determine whether treatment with EI-ASM was associated with pVL >1000/mL copies. Of 50 participants, 41 (82%) were taking carbamazepine (37 on monotherapy), and all had stable regimens in the prior 6months. Among the 13 ARV regimens used, 68% had a tenofovir/lamivudine backbone. The majority (94%) were on a stable ARV regimen for >6months. Median CD4 nadir was 205 cells/mm3 (interquartile range [IQR] 88-389), and 60% of participants had commenced ARV treatment before advanced disease occurred. Mean CD4 count at enrollment was 464cells/mm3 (SD 226.3). Seven participants (14%) had a CD4 count <200cells/mm3 . Four (8%) had a pVL >1000copies/mL; all were on carbamazepine. Three participants with elevated pVL had a CD4 count <200cells/mm3 . None had documented adherence concerns by providers; however, two had events concerning for clinical failure. HIV genotype testing showed mutations in three participants. Carbamazepine was not found to correlate with elevated pVL (P=.58). EI-ASMs are commonly used in sub-Saharan Africa. Despite concurrent use of EI-ASMs and ARVs, the majority of participants showed CD4 counts >200 cells/mm3 and were virally suppressed. Carbamazepine was not associated with an increased risk of virological failure or ARV-resistant HIV.

Cerebrovascular Disease in Children Perinatally Infected With Human Immunodeficiency Virus in Zambia

BackgroundHigh rates of cerebrovascular disease (CVD) have previously been described in pediatric human immunodeficiency virus (HIV). However, little is known about pediatric CVD in the era of antiretroviral therapy or about the contribution of CVD to HIV-associated neurocognitive disorders. MethodsWe completed a neuroimaging substudy of the HIV-Associated Neurocognitive Disorders in Zambia study, a prospective cohort study of neurocognitive complications of pediatric HIV. Brain magnetic resonance imaging (1.5 T) was acquired for 34 HIV+ children on antiretroviral therapy and 17 HIV-exposed uninfected children (aged eight to 17 years). Demographics, medical history, neurological examination, and neuropsychologic testing results were collected. Two neuroradiologists, unaware of HIV status and clinical course, read the scans. ResultsCVD was identified in seven of 34 children with HIV (HIV+ CVD+) and no HIV-exposed uninfected children (21% vs 0%, P = 0.05). Three participants had white matter changes suggestive of small vessel disease, four had infarcts, and two had evidence of intracranial artery stenosis. Age of antiretroviral therapy initiation and exposure to protease inhibitors or efavirenz was not significantly different between children with and without CVD. HIV+ CVD+ children had significantly worse scores on a summary measure of cognition than the HIV+ CVD− group (NPZ8 score −0.57 vs 0.33, P = 0.04). ConclusionsThis study demonstrates high rates of CVD in children with HIV despite antiretroviral therapy, and worse cognitive performance in children with CVD. Longitudinal studies are necessary to determine the mechanisms and incidence of new-onset CVD in children with HIV.

Brain Magnetic Resonance Imaging Findings Associated With Cognitive Impairment in Children and Adolescents With Human Immunodeficiency Virus in Zambia

BackgroundCognitive impairment is common in children and adolescents with human immunodeficiency virus (HIV). Brain magnetic resonance imaging (MRI) is a potentially useful tool to investigate the pathophysiology of HIV-associated cognitive impairment and may serve as a biomarker in future clinical trials. There are few published data on brain imaging in children with HIV in sub-Saharan Africa. MethodsThirty-four perinatally infected subjects with HIV and age-matched HIV-exposed uninfected controls between the ages nine and 17 years were recruited from the Pediatric Center of Excellence in Lusaka, Zambia, as part of the HIV-associated Neurocognitive Disorders in Zambia study. Brain MRI sequences were acquired, and clinical and volumetric assessments were performed. Subjects underwent a comprehensive neuropsychologic battery, and cognitive impairment status was classified using a global deficit score approach. Regression models were used to evaluate relationships between MRI findings and cognitive function. ResultsWe identified cerebrovascular disease in seven of 34 subjects with HIV compared with zero of 17 controls (21% vs 0%, P = 0.04). We also identified decreased total brain volumes (1036 vs 1162 cm3, P = 0.03) and decreased cortical thickness in the right temporal lobes (3.12 vs 3.29 mm; P = 0.01) and right fusiform gyri (3.10 vs 3.25 mm; P = 0.02) of HIV-infected subjects with cognitive impairment. ConclusionsThese findings support the hypothesis that brain volumes may be useful biomarkers for cognitive outcomes in children with HIV. Further studies are necessary to investigate mechanisms of cerebrovascular disease and volume loss in children with HIV.

Identifying Gaps in Prevention of Mother to Child Transmission of HIV: A Case Series of HIV-positive Infants in Zambia.

To determine the timing of prevention of mother-to-child transmission cascade programmatic barriers to understand the service gaps in preparation for scale up of Option B+ in the Southern Province of Zambia. A database search of the National Dried Blood Spot Registry in Zambia for DNA polymerase chain reaction identified human immunodeficiency virus (HIV)-infected infants from 5 facilities in 2 districts in Southern Province, Zambia over a 6-month observation period (January 2013 to June 2013). Seventeen HIV-positive infants out of 459 infants tested were identified from 5 health facilities that provided antiretroviral therapy (ART) initiation within the antenatal care (ANC) clinic, for a transmission rate of 3.7%. Possible risk factors identified for mother to child transmission of HIV included late ANC presentation, home delivery, provision of maternal short course prophylaxis, maternal refusal to initiate treatment and loss to follow-up. As Zambia transitions to life-long combination ART initiation for HIV-positive pregnant women under Option B+, and subsequent ART integration into ANC facilities, it is crucial to understand prevention of mother-to-child transmission program gaps to achieve the goal of eliminating mother to child transmission of HIV in Zambia.

Longitudinal adherence to antiretroviral drugs for preventing mother-to-child transmission of HIV in Zambia.

BackgroundAdherence to antiretroviral (ARV) drugs is essential for eliminating new pediatric infections of human immunodeficiency virus (HIV). Since the Zambian government revised the national guidelines based on option A (i.e., maternal zidovudine and infant ARV prophylaxis) of the World Health Organization’s 2010 guidelines, no studies have assessed adherence to ARVs during pregnancy up to the postpartum period. This study aimed to examine adherence to ARVs and identify the associated risk factors.MethodsA prospective cohort study was conducted in the Chongwe district from June 2011 to January 2014. Self-reported adherence to ARVs was examined during pregnancy and at one week, six weeks, and 24 weeks postpartum among 321 HIV-positive women. The probability of remaining adherent to ARVs was estimated using the Kaplan-Meier method, and the risk factors for non-adherence were identified using the Cox proportional hazard regressions—treating loss to follow-up as non-adherence. The statuses of HIV in HIV-exposed infants were assessed in January 2014.ResultsDuring the study period, 326 infants were born to HIV-positive women, 262 (80.4 %) underwent HIV testing, and 11 (3.4 %) had their HIV infection detected at the time that they had the latest HIV testing as of January 2014. The ARV adherence rate was 82.5 % during pregnancy, 84.2 % at one week postpartum, 81.5 % at six weeks postpartum, and 70.5 % at 24 weeks postpartum. The probability of remaining adherent to ARVs was 0.61 at day 50, 0.35 at day 100, 0.18 at day 200, and 0.06 at day 300. Attending a referral health center (HC) was a risk factor for non-adherence compared with attending rural HCs that provided HIV care/treatment (adjusted hazard ratio [aHR] 0.71, 95 % confidence interval [CI] 0.57–0.88) and those that did not provide HIV care/treatment (aHR 0.58, 95 % CI 0.46–0.74). A new diagnosis of HIV infection compared to a known HIV-positive status before pregnancy was another risk factor for non-adherence (aHR 1.24, 95 % CI 1.03–1.50).ConclusionsMaintaining adherence to ARVs through pregnancy to the postpartum period remains a crucial challenge in Zambia. To maximize the treatment benefits, adherence to ARVs and retention in care should be improved at all health facilities.

The Zambia Children's KS-HHV8 Study: Rationale, Study Design, and Study Methods

The epidemic of human immunodeficiency virus in Zambia has led to a dramatic rise in the incidence of human herpesvirus-8 (HHV-8)-associated Kaposi's sarcoma in both adults and children. However, there is a paucity of knowledge about the routes of HHV-8 transmission to young children. The Zambia Children's KS-HHV8 Study, a large, prospective cohort study in Lusaka, Zambia, was launched in 2004 to investigate the role of household members as a source of HHV-8 infection in young children and social behaviors that may modify the risk of HHV-8 acquisition. This cohort is distinct from other epidemiologic studies designed to investigate HHV-8 incidence and transmission because it recruited and followed complete households in the urban central African context. Between July 2004 and March 2007, 1,600 households were screened; 368 households comprising 464 children and 1,335 caregivers and household members were enrolled. Follow-up of this population continued for 48 months postrecruitment, affording a unique opportunity to study horizontal transmission of HHV-8 and understand the routes and sources of transmission to young children in Zambia. The authors describe the study rationale, design, execution, and characteristics of this cohort, which provides critical data on the epidemiology and transmission of HHV-8 to young children in Zambia.

Cancrum oris: management, incidence, and implications of human immunodeficiency virus in Zambia.

The University Teaching Hospital is situated in the Zambian capital, Lusaka. In a 15-year period (1979 to 1993), 81 child patients with cancrum oris were admitted to the pediatric plastic surgery unit. There were 29 boys and 52 girls, of whom 58 were below 3 years of age. The majority of them were from certain provinces where the population is comparatively much lower than in other provinces of Zambia. The dietary habits in cancrum orisprone provinces are quite different than those of other provinces of Zambia. Of 81 patients, 3 refused surgery, 11 died during early medical treatment, and 12 died following early minor surgery. A total of 55 patients had reconstructive surgery by one of the authors (Nath). Problems encountered during management, such as anesthesia, trismus, and choice of appropriate flaps, are discussed in this paper. The implication of human immunodeficiency virus is also addressed.