Suchergebnisse

IntroductionAs access to prevention of mother‐to‐child transmission (PMTCT) efforts has increased, the total number of children being born with HIV has significantly decreased. However, those children who do become infected after PMTCT failure are at particular risk of HIV drug resistance, selected by exposure to maternal or paediatric antiretroviral drugs used before, during or after birth. As a consequence, the response to antiretroviral therapy (ART) in these children may be compromised, particularly when non‐nucleoside reverse transcriptase inhibitors (NNRTIs) are used as part of the first‐line regimen. We review evidence guiding choices of first‐ and second‐line ART.DiscussionChildren generally respond relatively well to ART. Clinical trials show the superiority of protease inhibitor (PI)‐ over NNRTI‐based treatment in young children, but observational reports of NNRTI‐containing regimens are usually favourable as well. This is reassuring as national guidelines often still recommend the use of NNRTI‐based treatment for PMTCT‐unexposed young children, due to the higher costs of PIs. After failure of NNRTI‐based, first‐line treatment, the rate of acquired drug resistance is high, but HIV may well be suppressed by PIs in second‐line ART. By contrast, there are currently no adequate alternatives in resource‐limited settings (RLS) for children failing either first‐ or second‐line, PI‐containing regimens.ConclusionsAffordable salvage treatment options for children in RLS are urgently needed.

AbstractIntroductionPlacing all clients with a positive diagnosis for HIV on antiretroviral therapy (ART) has cost implications both for patients and health systems, which could, in turn, affect feasibility, sustainability and uptake of new services. Patient‐incurred costs are recognized barriers to healthcare access. Differentiated service delivery (DSD) models in general and community‐based care in particular, could reduce these costs. We aimed to assess patient‐incurred costs of a community‐based DSD intervention (clubs) compared to clinic‐based care in the Shinyanga region, Tanzania.MethodsCross‐sectional survey among stable ART patients (n = 390, clinic‐based; n = 251, club‐based). For each group, we collected socio‐demographic, income and expenditure data between May and August 2019. We estimated direct and indirect patient‐incurred costs. Direct costs included out‐of‐pocket expenditures. Indirect costs included income loss due to time spent during transport, accessing services and off work during illness. Cost drivers were assessed in multivariate regression models.ResultsOverall, costs were significantly higher among clinic participants. Costs (USD) per year for clinic versus club were as follows: 11.7 versus 4.17 (p < 0.001) for direct costs, 20.9 versus 8.23 (p < 0.001) for indirect costs and 32.2 versus 12.4 (p < 0.001) for total costs. Time spent accessing care and time spent in illness (hours/year) were 38.3 versus 13.8 (p < 0.001) and 16.0 versus 6.69 (p < 0.001) respectively. The main cost drivers included transportation (clinic vs. club: 67.7% vs. 44.1%) for direct costs and income loss due to time spent accessing care (clinic vs. club: 60.4% vs. 56.7%) for indirect costs. Factors associated with higher total costs among patients attending clinic services were higher education level (coefficient [95% confidence interval]) 20.9 [5.47 to 36.3]) and formal employment (44.2 [20.0 to 68.5). Differences in mean total costs remained significantly higher with formal employment, rural residence, in addition to more frequent visits among clinic participants. The percentage of households classified as having had catastrophic expenditures in the last year was low but significantly higher among clinic participants (10.8% vs. 5.18%, p = 0.014).ConclusionsCosts incurred by patients accessing DSD in the community are significantly lower compared to those accessing standard clinic‐based care. DSD models could improve access, especially in resource‐limited settings.

AbstractIntroductionThere is emerging data on HIV‐1 incidence among MSM in sub‐Saharan Africa (SSA), but no known estimate of HIV‐1 incidence among transgender women (TGW) in the region has yet been reported. We assessed HIV‐1 incidence and pre‐exposure prophylaxis (PrEP) interest in men who have sex with men exclusively (MSME), men who have sex with men and women (MSMW) and TGW in coastal Kenya.MethodsHIV‐1‐seronegative individuals who had participated in an HIV testing study in 2016 were traced and retested in 2017 according to Kenyan guidelines. All participants were assigned male sex at birth and had male sex partners; additional data on gender identity and sexual orientation were obtained. We assessed the factors associated with HIV‐1 acquisition using Poisson regression and calculated HIV‐1 incidence in MSME, MSMW and TGW. PrEP interest was assessed through focus group discussions to characterize subcategories' perceived PrEP needs.ResultsOf the 168 cohort participants, 42 were classified as MSME, 112 as MSMW and 14 as TGW. Overall, HIV‐1 incidence was 5.1 (95% confidence interval (CI): 2.6 to 9.8) per 100 person‐years (PY): 4.5 (95% CI: 1.1 to 17.8] per 100 PY among MSME, 3.4 (95% CI: 1.3 to 9.1) per 100 PY among MSMW and 20.6 (95% CI: 6.6 to 63.8] per 100 PY among TGW. HIV‐1 acquisition was associated with exclusive receptive anal intercourse (aIRR 13.0, 95% CI 1.9 to 88.6), history of an STI in preceding six months (aIRR 10.3, 95% CI 2.2 to 49.4) and separated/divorced marital status (aIRR 8.2 (95%: 1.1 to 62.2). Almost all (98.8%) participants were interested in initiating PrEP. MSME and TGW felt that PrEP would lead to increases in condomless anal or group sex.ConclusionsTGW had a very high HIV‐1 incidence compared with MSME and MSMW. Subcategories of MSM anticipated different PrEP needs and post‐PrEP risk behaviour. Further studies should assess if TGW may have been wrongly categorized as MSM in other HIV‐1 incidence studies in the region.

IntroductionPre‐treatment HIV drug resistance (PDR) is an increasing problem in sub‐Saharan Africa. Children are an especially vulnerable population to develop PDR given that paediatric second‐line treatment options are limited. Although monitoring of PDR is important, data on the paediatric prevalence in sub‐Saharan Africa and its consequences for treatment outcomes are scarce. We designed a prospective paediatric cohort study to document the prevalence of PDR and its effect on subsequent treatment failure in Nigeria, the country with the second highest number of HIV‐infected children in the world.MethodsHIV‐1‐infected children ≤12 years, who had not been exposed to drugs for the prevention of mother‐to‐child transmission (PMTCT), were enrolled between 2012 and 2013, and followed up for 24 months in Lagos, Nigeria. Pre‐antiretroviral treatment (ART) population‐based pol genotypic testing and six‐monthly viral load (VL) testing were performed. Logistic regression analysis was used to assess the effect of PDR (World Health Organization (WHO) list for transmitted drug resistance) on subsequent treatment failure (two consecutive VL measurements >1000 cps/ml or death).ResultsOf the total 82 PMTCT‐naïve children, 13 (15.9%) had PDR. All 13 children harboured non‐nucleoside reverse transcriptase inhibitor (NNRTI) mutations, of whom seven also had nucleoside reverse transcriptase inhibitor resistance. After 24 months, 33% had experienced treatment failure. Treatment failure was associated with PDR and a higher log VL before treatment initiation (adjusted odds ratio (aOR) 7.53 (95%CI 1.61–35.15) and 2.85 (95%CI 1.04–7.78), respectively).DiscussionPDR was present in one out of six Nigerian children. These high numbers corroborate with recent findings in other African countries. The presence of PDR was relevant as it was the strongest predictor of first‐line treatment failure.ConclusionsOur findings stress the importance of implementing fully active regimens in children living with HIV. This includes the implementation of protease inhibitor (PI)‐based first‐line ART, as is recommended by the WHO for all HIV‐infected children <3 years of age. Overcoming practical barriers to implement PI‐based regimens is essential to ensure optimal treatment for HIV‐infected children in sub‐Saharan Africa. In countries where individual VL or resistance testing is not possible, more attention should be given to paediatric PDR surveys.

AbstractIntroduction: Our understanding of how to achieve optimal long‐term adherence to antiretroviral therapy (ART) in settings where the burden of HIV disease is highest remains limited. We compared levels and determinants of adherence over time between HIV‐positive persons receiving ART who were enrolled in a bi‐regional cohort in sub‐Saharan Africa and Asia.Methods: This multicentre prospective study of adults starting first‐line ART assessed patient‐reported adherence at follow‐up clinic visits using a 30‐day visual analogue scale. Determinants of suboptimal adherence (<95%) were assessed for six‐month intervals, using generalized estimating equations multivariable logistic regression with multiple imputations. Region of residence (Africa vs. Asia) was assessed as a potential effect modifier.Results: Of 13,001 adherence assessments in 3934 participants during the first 24 months of ART, 6.4% (837) were suboptimal, with 7.3% (619/8484) in the African cohort versus 4.8% (218/4517) in the Asian cohort (p < 0.001). In the African cohort, determinants of suboptimal adherence were male sex (odds ratio (OR) 1.27, 95% confidence interval (CI) 1.06–1.53; p = 0.009), younger age (OR 0.8 per 10 year increase; 0.8–0.9; p = 0.003), use of concomitant medication (OR 1.8, 1.0–3.2; p = 0.044) and attending a public facility (OR 1.3, 95% CI 1.1–1.7; p = 0.004). In the Asian cohort, adherence was higher in men who have sex with men (OR for suboptimal adherence 0.6, 95% CI 0.4–0.9; p = 0.029) and lower in injecting drug users (OR for suboptimal adherence 1.6, 95% CI 0.9–2.6; p = 0.075), compared to heterosexuals. Risk of suboptimal adherence decreased with longer ART duration in both regions. Participants in low‐ and lower‐middle‐income countries had a higher risk of suboptimal adherence (OR 1.6, 1.3–2.0; p < 0.001), compared to those in upper‐middle or high‐income countries. Suboptimal adherence was strongly associated with virological failure, in Africa (OR 5.8, 95% CI 4.3–7.7; p < 0.001) and Asia (OR 9.0, 95% CI 5.0–16.2; p < 0.001). Patient‐reported adherence barriers among African participants included scheduling demands, drug stockouts, forgetfulness, sickness or adverse events, stigma or depression, regimen complexity and pill burden.Conclusions: Psychosocial factors and health system resources may explain regional differences. Adherence‐enhancing interventions should address patient‐reported barriers tailored to local settings, prioritizing the first years of ART.

AbstractIntroduction: The number of HIV‐infected children and adolescents requiring second‐line antiretroviral treatment (ART) is increasing in low‐ and middle‐income countries (LMIC). However, the effectiveness of paediatric second‐line ART and potential risk factors for virologic failure are poorly characterized. We performed an aggregate analysis of second‐line ART outcomes for children and assessed the need for paediatric third‐line ART.Methods: We performed a multicentre analysis by systematically reviewing the literature to identify cohorts of children and adolescents receiving second‐line ART in LMIC, contacting the corresponding study groups and including patient‐level data on virologic and clinical outcomes. Kaplan–Meier survival estimates and Cox proportional hazard models were used to describe cumulative rates and predictors of virologic failure. Virologic failure was defined as two consecutive viral load measurements >1000 copies/ml after at least six months of second‐line treatment.Results: We included 12 cohorts representing 928 children on second‐line protease inhibitor (PI)‐based ART in 14 countries in Asia and sub‐Saharan Africa. After 24 months, 16.4% (95% confidence interval (CI): 13.9–19.4) of children experienced virologic failure. Adolescents (10–18 years) had failure rates of 14.5 (95% CI 11.9–17.6) per 100 person‐years compared to 4.5 (95% CI 3.4–5.8) for younger children (3–9 years). Risk factors for virologic failure were adolescence (adjusted hazard ratio [aHR] 3.93, p < 0.001) and short duration of first‐line ART before treatment switch (aHR 0.64 and 0.53, p = 0.008, for 24–48 months and >48 months, respectively, compared to <24 months).Conclusions: In LMIC, paediatric PI‐based second‐line ART was associated with relatively low virologic failure rates. However, adolescents showed exceptionally poor virologic outcomes in LMIC, and optimizing their HIV care requires urgent attention. In addition, 16% of children and adolescents failed PI‐based treatment and will require integrase inhibitors to construct salvage regimens. These drugs are currently not available in LMIC.