The prevalence of nevirapine toxicity among pregnant women in three health facilities in Johannesburg: 2004 to 2008 and 2010 to 2011

Submitted in partial fulfilment of the requirements for the degree of Master of Public Health, in the field of Maternal and Child Health, to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, September 2014Introduction: Nevirapine (NVP) is used in combination antiretroviral treatment especially for pregnant HIV infected women. NVP has been shown to be inferior and more toxic than other similar drugs, but continues to be used in developing countries due to cost. Aim: This study aimed to determine the prevalence of NVP toxicity and associated factors among 478 pregnant women from three public health facilities in inner city Johannesburg. Materials and methods: We employed a cross-sectional retrospective record review study design to analyse the records of 478 pregnant women in the above mentioned public health facilities. Variables including demographic (age, weight, gestational age) and clinical (CD4 cell count, WHO HIV clinical stage, prior ART experience) characteristics were extracted and the association between these characteristics and the development of toxicity post NVP exposure was explored. Results: The study found that approximately nine out of ten women (89.5%) were ART naïve at the time of NVP initiation. When compared with ART naïve women, ART experienced women had a slightly higher mean CD4 cell count, however, for both groups of women, mean CD4 cell count was less than 250 cells/mm3. Overall, 85.1% of women had a CD4 cell count less than 250 cells/mm3. More than half (55.3%) of the women were in the third trimester of pregnancy and the majority (82%) classified as WHO HIV clinical stage one. At least one adverse event was reported in 63 (13.2%) women. Mild skin rash was the most prevalent adverse event, occurring in 9.6% of women. Hepatotoxicity occurred in 5.3% of women and severe skin rash occurred in 1.5% of women. Almost 85% of adverse events occurred in women with CD4 cell counts <250 cells/mm3. WHO HIV clinical stage II and IV were significantly associated with the overall development of toxicity (ρ <0.01). Conclusions: Whilst the overall prevalence of mild and severe skin rash in this sample was less than that demonstrated in earlier studies, a higher overall prevalence of hepatotoxicity was found. When compared with ART naïve women, ART experienced women were found to have a higher prevalence of mild skin rash. Hepatotoxicity and severe skin rash only occurred in ART naïve women. In this sample, CD4 cell count ≥250 cells/mm3 was not associated with the development of NVP adverse events. Recommendations: Our findings support the continued use of NVP as part of combination ART regimens in women of African descent. In contrast with previously published data, our study showed a significant association between WHO HIV clinical stage and NVP toxicity, our study also included relatively few women with higher CD4 cell counts. Further research including predominantly healthy HIV infected pregnant African women as well as women with higher CD4 cell counts is required in order to fully explore the association between these variables and the development of NVP post-exposure toxicity

Risk Factors for Hypoxia and Tachypnea Among Adolescents With Vertically-acquired HIV in Nairobi

Background: Chronic lung diseases are increasingly recognized complications of vertically-acquired HIV among adolescents in sub-Saharan Africa and may manifest with hypoxia or tachypnea. We sought to determine the prevalence of and risk factors for hypoxia and tachypnea among adolescents with vertically-acquired HIV in Nairobi, Kenya. Methods: We performed a cross-sectional analysis of 258 adolescents with vertically-acquired HIV who were initiating care at the Coptic Hope Center for Infectious Diseases. Adolescents with documented pneumonia were excluded. Hypoxia was defined as resting oxygen saturation ≤92%, and tachypnea was based on the 99th percentile of age-appropriate respiratory rates. Logistic regression models adjusted for demographics, and HIV severity estimated odds ratios for risk of hypoxia and tachypnea associated with potential risk factors. Results: Overall, 11% of adolescents had hypoxia and 55% had tachypnea. Advanced HIV [adjusted odds ratio (aOR): 2.41] and low CD4 (aOR: 1.74) were associated with greater hypoxia risk, but confidence intervals (CIs) were wide and included the null (95% CI: 0.93–6.23 and 0.69–4.39, respectively). Low CD4 (aOR: 2.45, 95% CI: 1.39–4.32), current antiretroviral therapy use (aOR: 0.48, 95% CI: 0.27–0.86) and stunted growth (aOR: 3.46, 95% CI: 1.94–6.18) were associated with altered tachypnea risk. Conclusions: Hypoxia and tachypnea are common among adolescents with vertically-acquired HIV. There was a suggestion that advanced HIV and low CD4 were associated with greater hypoxia risk. Low CD4, lack of antiretroviral therapy use and stunted growth are risk factors for tachypnea. Our findings highlight the chronic lung disease burden in this population and may inform diagnostic algorithms

A Cluster-Randomised Trial to Compare Home-Based with Health Facility-Based Antiretroviral Treatment in Uganda: Study Design and Baseline Findings

The scale-up of antiretroviral therapy is progressing rapidly in Africa but with a limited evidence-base. We report the baseline results from a large pragmatic cluster-randomised trial comparing different strategies of ART delivery. The trial is integrated in normal health service delivery. 1453 subjects were recruited into the study. Significantly more women (71%) than men (29%) were recruited. The WHO HIV clinical stage at presentation did not differ significantly between men and women: 58% and 53% respectively were at WHO stage III or IV (p=0.9). Median CD4 counts (IQR) x 106cells/l were 98 (28, 160) among men and 111 (36, 166) among women. Sixty-four percent of women and 61% men had plasma viral load ≥100,000 copies. Baseline characteristics did not change over time. Considerably fewer men than women presented for treatment. Both men and women presented at an advanced stage with very low median CD4 count and high plasma viral load

Treatment Buddies Improve Clinic Attendance among Women but Not Men on Antiretroviral Therapy in the Nyanza Region of Kenya.

Background. Kenyan antiretroviral (ART) guidelines encourage treatment buddies (TBy) to maximize treatment adherence. This study examined the effect of TBys on clinic attendance in men and women on ART. Methods. This retrospective cohort study included all adult patients initiating ART from August 2007 to December 2011 at four health facilities in Kenya. Data were abstracted from electronic medical records and analyzed using Poisson regression. Results. Of 2,430 patients, 2,199 (91%) had a TBy. Relationship between TBy and clinic attendance differed in females and males (interaction p = 0.09). After demographic and clinic factor adjustment, females with a TBy were 28% more likely to adhere to all appointments than those without (adjusted aRR = 1.28; 95% CI 1.08-1.53), whereas males were no more likely to adhere (aRR = 1.01; 95% CI 0.76-1.32). Males reported partner/spouse (33%) or brother (11%) as the TBy while females reported sister (17%), partner/spouse (14%), or another family member (12%). Multivariable analysis found no association between clinic attendance and TBy relationship in either gender. Conclusion. Clinic attendance was higher among women with TBys but not men. Results support TBys to help women achieve ART success; alternate strategies to bolster TBy benefits are needed for men

Agreement and Discrepancy on Emotional and Behavioral Problems Between Caregivers and HIV-Infected Children and Adolescents From Uganda.

Background: HIV-infected children and adolescents (CA-HIV) face significant mental health challenges related to a broad range of biological and psychosocial factors. Data are scarce on the agreement and discrepancy between caregivers and CA-HIV regarding emotional and behavioral problems (EBPs) in CA-HIV. Objectives: We determined agreement between self- versus caregiver- reported EBPs and describe factors associated with informant discrepancy among caregiver-youth dyads who participated in the "Mental health among HIV-infected CHildren and Adolescents in KAmpala and Masaka, Uganda" (CHAKA) study. Methods: In a cross-sectional sample, caregiver-reported EBPs were assessed with the Child and Adolescent Symptom Inventory-5 (CASI-5), and self-reported problems were evaluated with the Youth Inventory-4 (YI-4) in 469 adolescents aged 12-17 years and the Child Inventory-4 (CI-4) in 493 children aged 8-11 years. Adolescents were questioned about experiences of HIV stigma. Caregiver psychological distress was assessed with the Self-Reporting Questionnaire (SRQ-20). Linear regression models were applied to identify variables associated with discrepancy scores. Results: Self-reported emotional problems (EPs) were present in 28.8% of adolescents and 36.9% of children, and 14.5% of adolescents self-reported behavioral problems (BPs). There was only a modest correlation (r ≤ 0.29) between caregiver- and CA-HIV-reported EBPs, with caregivers reporting more EPs whereas adolescents reported more BPs. Informant discrepancy between adolescents and caregivers for BPs was associated with adolescent age and caregiver's employment and HIV status. Among adolescents, EP discrepancy scores were associated with adolescent's WHO HIV clinical stage, caregiver level of education, and caregivers caring for other children. Among children, EP discrepancy scores were associated with child and caregiver age, caregiver level of education, and caregiver self-rated health status. HIV stigma and caregiver psychological distress were also associated with discrepancy, such that adolescents who experienced HIV stigma rated their EPs as more severe than their caregivers did and caregivers with increased psychological distress rated EBPs as more severe than CA-HIV self-rated. Conclusions: EBPs are frequently endorsed by CA-HIV, and agreement between informants is modest. Informant discrepancy is related to unique psychosocial and HIV-related factors. Multi-informant reports enhance the evaluation of CA-HIV and informant discrepancies can provide additional insights into the mental health of CA-HIV

Integration of family planning services into HIV care clinics: Results one year after a cluster randomized controlled trial in Kenya.

OBJECTIVES:To determine if integration of family planning (FP) and HIV services led to increased use of more effective contraception (i.e. hormonal and permanent methods, and intrauterine devices) and decreased pregnancy rates. DESIGN:Cohort analysis following cluster randomized trial, when the Kenya Ministry of Health led integration of the remaining control (delayed integration) sites and oversaw integrated services at the original intervention (early integration) sites. SETTING:Eighteen health facilities in Kenya. SUBJECTS:Women aged 18-45 receiving care: 5682 encounters at baseline, and 11628 encounters during the fourth quarter of year 2. INTERVENTION:"One-stop shop" approach to integrating FP and HIV services. MAIN OUTCOME MEASURES:Use of more effective contraceptive methods and incident pregnancy across two years of follow-up. RESULTS:Following integration of FP and HIV services at the six delayed integration clinics, use of more effective contraception increased from 31.7% to 44.2% of encounters (+12.5%; Prevalence ratio (PR) = 1.39 (1.19-1.63). Among the twelve early integration sites, the proportion of encounters at which women used more effective contraceptive methods was sustained from the end of the first to the second year of follow-up (37.5% vs. 37.0%). Pregnancy incidence including all 18 integrated sites in year two declined in comparison to the control arm in year one (rate ratio: 0.72; 95% CI 0.60-0.87). CONCLUSIONS:Integration of FP services into HIV clinics led to a sustained increase in the use of more effective contraceptives and decrease in pregnancy incidence 24 months following implementation of the integrated service model. TRIAL REGISTRATION:ClinicalTrials.gov NCT01001507

Low mortality rates at two years in HIV-infected individuals undergoing systematic tuberculosis testing with rapid assays at initiation of antiretroviral treatment in Mozambique

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