Virologic response of treatment experienced HIV-infected Ugandan children and adolescents on NNRTI based first-line regimen, previously monitored without viral load.

BACKGROUND: Many HIV-infected African children gained access to antiretroviral treatment (ART) through expansion of PEPFAR programs since 2004 and introduction of "Test and Treat" WHO guidelines in 2015. As ART access increases and children transition from adolescence to adulthood, treatment failure is inevitable. Viral load (VL) monitoring in Uganda was introduced in 2016 replacing clinical monitoring. However, there's limited data on the comparative effectiveness of these two strategies among HIV-infected children in resource-limited settings (RLS). METHODS: HIV-infected Ugandan children aged 1-12 years from HIV-care programs with > 1 year of first-line ART using only immunologic and clinical criteria to monitor response to treatment were screened in 2010. Eligible children were stratified by VL ≤ 400 and > 400 copies/ml randomized to clinical and immunological (control) versus clinical, immunological and VL monitoring to determine treatment failure with follow-up at 12, 24, 36, and 48 weeks. Plasma VL was analyzed retrospectively for controls. Mixed-effects logistic regression models were used to compare the prevalence of viral suppression between study arms and identify factors associated with viral suppression. RESULTS: At baseline all children (n = 142) were on NNRTI based ART (75% Nevirapine, 25% efavirenz). One third of ART-experienced children had detectable VL at baseline despite high CD4%. Median age was 6 years (interquartile range [IQR]: 5-9) and 43% were female. Overall, the odds of viral suppression were not different between study arms: (arm by week interaction, p = 0.63), adjusted odds ratio [aOR]: 1.07; 95%CI: 0.53, 2.17, p = 0.57) and did not change over time (aOR: 0 vs 24 week: 1.15; 95% CI: 0.91, 1.46, p = 0.24 and 0 vs 48 weeks: 1.26; 95%CI: 0.92, 1.74, p = 0.15). Longer duration of a child's ART exposure was associated with lower odds of viral suppression (aOR: 0.61; 95% CI: 0.42, 0.87, p < .01). Only 13% (9/71) of children with virologic failure were switched to second-line ART, in spite of access to real-time VL. CONCLUSION: With increasing ART exposure, viral load monitoring is critical for early detection of treatment failure in RLS. Clinicians need to make timely informed decisions to switch failing children to second-line ART. TRIAL REGISTRATION: ClinicalTrials.gov NCT04489953 , 28 Jul 2020. Retrospectively registered. ( https://register.clinicaltrials.gov ).

Fertility desires and unmet need for family planning among HIV infected individuals in two HIV clinics with differing models of family planning service delivery.

BACKGROUND: Eliminating family planning (FP) unmet need among HIV-infected individuals (PLHIV) is critical to elimination of mother-to-child HIV transmission. We assessed FP unmet need among PLHIV attending two clinics with differing models of FP services. Nsambya Home Care provided only FP information while Mulago HIV clinic provided information and contraceptives onsite. METHODS: In a cross-sectional study conducted between February-June 2011, we documented pregnancies, fertility desires, and contraceptive use among 797 HIV-infected men and women (408 in Mulago and 389 in Nsambya). FP unmet need was calculated among women who were married, unmarried but had sex within the past month, did not desire the last or future pregnancy at all or wished to postpone for ≥ two years and were not using contraceptives. Multivariable analyses for correlates of FP unmet need were computed for each clinic. RESULTS: Overall, 40% (315) had been pregnant since HIV diagnosis; 58% desired the pregnancies. Of those who were not pregnant, 49% (366) did not desire more children at all; 15.7% wanted children then and 35.3% later. The unmet need for FP in Nsambya (45.1%) was significantly higher than that in Mulago at 30.9% (p = 0.008). Age 40+ compared to 18-29 years (OR = 6.05; 95% CI: 1.69, 21.62 in Mulago and OR = 0.21; 95% CI: 0.05, 0.90 in Nsambya), other Christian denominations (Pentecostal and Seventh Day Adventists) compared to Catholics (OR = 7.18; 95% CI: 2.14, 24.13 in Mulago and OR = 0.23; 95% CI: 0.06, 0.80 in Nsambya), and monthly expenditure > USD 200 compared to < USD40 in Nsambya (OR = 0.17; 95% CI: 0.03, 0.90) were associated with FP unmet need. CONCLUSIONS: More than half of the pregnancies in this population were desired. Unmet need for FP was very high at both clinics and especially at the clinic which did not have contraceptives onsite. Lower income and younger women were most affected by the lack of contraceptives onsite. Comprehensive and aggressive FP programs are required for fertility support and elimination of FP unmet need among PLHIV, even with integration of FP information and supplies into HIV clinics.

Epstein-Barr virus load in children infected with human immunodeficiency virus type 1 in Uganda.

BACKGROUND: Epstein-Barr Virus (EBV) is involved in a wide range of malignancies, particularly in immunocompromised subjects. In Africa, EBV primary infection occurs during early childhood, but little is known about the EBV load in Human Immunodeficiency Virus type 1 (HIV-1)-infected children. METHODS: Blood samples from 213 HIV-1-infected children, 140 of whom were receiving antiretroviral therapy (ART), were collected at the Nsambya Hospital in Kampala, Uganda, and obtained for dried blood spot analysis. Nucleic acids were extracted and analyzed for quantification of EBV types 1 and 2; 16S ribosomal DNA (rDNA), a marker of microbial translocation; and HIV-1 RNA. RESULTS: Ninety-two of 140 children (66%) receiving ART and 57 of 73 ART-naive children (78%) had detectable EBV DNA levels. Coinfection with both EBV types was less frequent in ART-treated children than in ART-naive children (odds ratio, 0.54 [95% confidence interval {CI}, .30-.98]; P = .042). Mean EBV DNA levels (±standard deviation) were lower in the former (3.99 ± 0.59 vs 4.22 ± 0.54 log10 copies/mL; P = .006) and tended to be inversely associated with ART duration. EBV DNA levels were higher in children with an HIV-1 RNA load of > 3 log10 copies/mL of blood (regression coefficient, 0.32 [95% CI, .05-.59]; P = .020) and correlated with circulating 16S rDNA levels (rs = 0.25 [95% CI, .02-.46]; P = .031). CONCLUSIONS: These findings suggest that ART, by limiting HIV-1 replication, microbial translocation, and related immune activation, prevents superinfection with both EBV types and keeps EBV viremia down, thus potentially reducing the risk of EBV-associated lymphomas.

Fertility and contraceptive decision-making and support for HIV infected individuals: client and provider experiences and perceptions at two HIV clinics in Uganda.

BACKGROUND: Some people living with HIV/AIDS (PLHIV) want to have children while others want to prevent pregnancies; this calls for comprehensive services to address both needs. This study explored decisions to have or not to have children and contraceptive preferences among PLHIV at two clinics in Uganda. METHODS: This was a qualitative cross-sectional study. We conducted seventeen focus group discussions and 14 in-depth interviews with sexually active adult men and women and adolescent girls and boys, and eight key informant interviews with providers. Overall, 106 individuals participated in the interviews; including 84 clients through focus group discussions. Qualitative latent content analysis technique was used, guided by key study questions and objectives. A coding system was developed before the transcripts were examined. Codes were grouped into categories and then themes and subthemes further identified. RESULTS: In terms of contraceptive preferences, clients had a wide range of preferences; whereas some did not like condoms, pills and injectables, others preferred these methods. Fears of complications were raised mainly about pills and injectables while cost of the methods was a major issue for the injectables, implants and intrauterine devices. Other than HIV sero-discordance and ill health (which was cited as transient), the decision to have children or not was largely influenced by socio-cultural factors. All adult men, women and adolescents noted the need to have children, preferably more than one. The major reasons for wanting more children for those who already had some were; the sex of the children (wanting to have both girls and boys and especially boys), desire for large families, pressure from family, and getting new partners. Providers were supportive of the decision to have children, especially for those who did not have any child at all, but some clients cited negative experiences with providers and information gaps for those who wanted to have children. CONCLUSIONS: These findings show the need to expand family planning services for PLHIV to provide more contraceptive options and information as well as expand support for those who want to have children.

Stigma mastery in people living with HIV: gender similarities and theory.

Aims: This study aimed to determine the prevalence of, factors associated with, and to build a theoretical framework for understanding Internalsed HIV-related Stigma Mastery (IHSM). Methods: A cross-sectional study nested within a 2014 Stigma Reduction Cohort in Uganda was used. The PLHIV Stigma Index version 2008, was used to collect data from a random sample of 666 people living with HIV (PLHIV) stratified by gender and age. SPSS24 with Amos27 softwares were used to build a sequential-mediation model. Results: The majority of participants were women (65%), aged ≥ 40 years (57%). Overall, IHSM was 45.5% among PLHIV, that increased with age. Specifically, higher IHSM correlated with men and older women "masculine identities" self-disclosure of HIV-diagnosis to family, sharing experiences with peers. However, lower IHSM correlated with feminine gender, the experience of social exclusion stress, fear of future rejection, and fear of social intimacy. Thus, IHSM social exclusion with its negative effects and age-related cognition are integrated into a multidimensional IHSM theoretical framework with a good model-to-data fit. Conclusion: Internalised HIV-related Stigma Mastery is common among men and older women. Specificially, "masculine identities" self-disclose their own HIV-positive diagnosis to their family, share experiences with peers to create good relationships for actualising or empowerment in stigma mastery. However, social exclusion exacerbates series of negative effects that finally undermine stigma mastery by young feminine identities. Thus, stigma mastery is best explained by an integrated empowerment framework, that has implications for future practice, policy, and stigma-related research that we discuss.

Incidence and short term outcomes of neonates with hypoxic ischemic encephalopathy in a Peri Urban teaching hospital, Uganda: a prospective cohort study.

BACKGROUND: Hypoxic Ischemic Encephalopathy carries high case fatality rates ranging between 10-60%, with 25% of survivors have an adverse long-term neurodevelopment outcome. Despite the above, there is paucity of data regarding its magnitude and short term outcomes in a low resource setting like Uganda. Therefore we set out to determine the incidence and short term outcomes of Newborns with Hypoxic Ischemic Encephalopathy at St.Francis Hospital, Nsambya. METHODS: This was a Prospective Cohort study conducted between October 2015 and January 2016 at St. Francis Hospital, Nsambya, Kampala- Uganda. Term Newborn babies were enrolled. Umbilical cord arterial blood gas analysis was done for Newborns with low Apgar scores at 5 min. Clinical examination was done on all newborns within 48 h of life, for features of encephalopathy. Neonates with Hypoxic Ischemic Encephalopathy were followed up by a daily clinical examination and a short term outcome was recorded on day seven. RESULTS: The incidence of Hypoxic Ischemic Encephalopathy was 30.6 cases per 1000 live births. The majority, 10 (43.5%) had mild Hypoxic Ischemic Encephalopathy, followed by 8 (34.8%), 5 (21.7%) that had moderate and severe Hypoxic Ischemic Encephalopathy respectively. A total of (6) 26% died, and (15) 65.2% were discharged within 1 week. Lack of a nutritive suckling reflex (nasogastric feeding), poor Moro reflex, and requirement for respiratory support (oxygen therapy by nasal prongs) were the common complications by day seven. CONCLUSIONS: The burden of Hypoxic Ischemic Encephalopathy is high with a case fatality rate of 26%. There is need to conduct a longitudinal study to determine the long term complications of HIE.

Predictors of Treatment Failure in HIV-Positive Children Receiving Combination Antiretroviral Therapy: Cohort Data From Mozambique and Uganda.

BACKGROUND: Delays detecting treatment failure and switching to second-line combination antiretroviral therapy (cART) are often observed in human immunodeficiency virus (HIV)-infected children of low-middle-income countries (LMIC). METHODS: An observational study included HIV-infected children attending the Beira Central Hospital (Mozambique) and the Nsambya Hospital, Home Care Department (Uganda) evaluated clinical and immunological failure according to World Health Organization (WHO) 2006 guidelines. Baseline predictors for cART failure and for drug substitution were explored in unadjusted and adjusted Cox proportional hazard models. RESULTS: Two hundred eighteen of 740 children with at least 24 weeks follow-up experienced treatment failure (29%; 95% confidence interval [CI] 26-33), with crude incidence of 20.0 events per 100 person-years (95% CI 17.5-22.9). Having tuberculosis co-infection or WHO stage 4, or starting a nontriple cART significantly increased risk of failure. Two hundred two of 769 (26.3%) children receiving cART substituted drug(s), with crude incidence of 15.4 events per 100 person-years (95% CI 13.4-17.7). Drug toxicity (18.3%), drug availability (17.3%), and tuberculosis drugs interaction (52, 25.7%) were main reported reasons, while only 9 (4%) patients switched cART for clinical or immunological failure. Children starting lamivudine-zidovudine-nevirapine or lamivudine-stavudine-efavirenz or lamivudine-zidovudine-efavirenz were more likely to have substitute drugs. Increased substitution was found in children with mild immunosuppression and tuberculosis co-infection at cART initiation as well as poor adherence before drug substitution. CONCLUSIONS: Considerable delay in switching to second-line cART may occur despite an observed high rate of failure. Factors including WHO clinical stage and tuberculosis co-infection should be evaluated before starting cART. Toxicity and drug adherence should be monitored to minimize drug substitution in LMIC.

Programmatic impact of the evolution of WHO pediatric antiretroviral treatment guidelines for resource-limited countries (Tukula Fenna Project, Uganda).

BACKGROUND: World Health Organization (WHO) recommendations for the initiation of antiretroviral therapy (ART) in children were revised in 2010, but the programmatic impact has had limited study. METHODS: We used a cohort of 985 Ugandan children followed since 2003 by the Tukula Fenna project to model the differential impact of the 2006, 2008, and 2010 WHO pediatric ART inititation criteria on the proportion of children eligible for ART at enrollment and over time. RESULTS: Using the WHO 2006, 2008, and 2010 ART criteria, 40%, 57%, and 66% of children, respectively, would have been eligible for ART at enrollment and 76%, 84%, and 88% 2 years later. Evaluating the entire cohort followed for 6 years using the 2006, 2008, and 2010 guidelines, the proportion in need of ART was found to be 70%, 82%, and 87%, respectively. Between 2006 and 2008, the proportions of eligible children starting ART within 6 and 12 months were 39% and 50%, respectively; after this, the proportions starting within 6 and 12 months were 50% and 52%. Before 2008, the most common criterion met in children who did not start ART was WHO clinical stage (odds ratio = 2.0, CI 95% = 1.2 to 3.2); after the 2008 recommendations, the most common eligibility criterion in children who did not start ART was age <12 months (odds ratio = 10.5, CI 95% = 3.8 to 31.1). CONCLUSIONS: An overall increase of 17% (from 70% to 87%) in children in need of ART was observed in our cohort comparing the 2006 and 2010 guidelines; this increase was primarily driven by the introduction of universal treatment for infants <12 months in 2008.

Prolonged elevation of viral loads in HIV-1-infected children in a region of intense malaria transmission in Northern Uganda: a prospective cohort study.

INTRODUCTION: Malaria and HIV-1 infection cause significant morbidity and mortality in children in sub-Saharan Africa. Recurrent malaria infection increases HIV-1 viral load in adults and increases the rate of progression of HIV-1 infection to AIDS. The effect of malaria on viral loads in children living with AIDS (CLWA) is not clearly known. METHODS: One hundred thirty five afebrile HIV-1 positive children having negative blood slides for malaria were recruited at Apac Hospital and followed up for one year. They were monitored for development of Plasmodium falciparum malaria, which was treated with chloroquine (CQ) + sulfadoxine-pyrimethamine (SP) and the children followed up for 28 days. HIV-1 viral loads were measured over three time-points: at enrolment (no malaria), during an episode of malaria, and at a visit about 8 weeks (range 6-19 weeks) after the malaria visit when the child had neither parasites nor any intervening malaria episodes (post-malaria). Primary analyses were restricted to children who on follow up had HIV-1 viral loads measured at the three relevant time-points. RESULTS: Malaria increased HIV-1 viral load significantly in CLWA. Low parasitemia (200-4000/Cl) transiently increased viral load by 0.42 log (95% CI 0.29-0.78, p = 0.0002), higher than that reported in adults. These patients' viral loads returned to levels similar to those at baseline after treatment. In 13 patients with high parasitemia (>4000/Cl), the mean increase in viral load was 0.53 log (95% CI 0.14 to 0.51), p<0.0001, remaining significantly higher than at baseline after treatment i.e. mean difference (signed-rank test) in viral load "before" and "after" malaria was significant. CONCLUSION: Plasmodium falciparum malaria is associated with increasing HIV-1 viral loads in children, with some viral loads remaining significantly elevated several weeks after antimalarial treatment. Prolonged post-treatment elevation has important implications for the clinical course in pre-ART HIV-1 positive children and the potential for transmission in sexually active adults.