BackgroundEvidence favoring earlier HIV ART initiation at high CD4+ T-cell counts (CD4>350/uL) has grown, and guidelines now recommend earlier HIV treatment. However, the cost of providing ART to individuals with CD4>350 in Sub-Saharan Africa has not been well estimated. This remains a major barrier to optimal global cost projections for accelerating the scale-up of ART. Our objective was to compute costs of ART delivery to high CD4+count individuals in a typical rural Ugandan health center-based HIV clinic, and use these data to construct scenarios of efficient ART scale-up.MethodsWithin a clinical study evaluating streamlined ART delivery to 197 individuals with CD4+ cell counts >350 cells/uL (EARLI Study: NCT01479634) in Mbarara, Uganda, we performed a micro-costing analysis of administrative records, ART prices, and time-and-motion analysis of staff work patterns. We computed observed per-person-per-year (ppy) costs, and constructed models estimating costs under several increasingly efficient ART scale-up scenarios using local salaries, lowest drug prices, optimized patient loads, and inclusion of viral load (VL) testing.FindingsAmong 197 individuals enrolled in the EARLI Study, median pre-ART CD4+ cell count was 569/uL (IQR 451–716). Observed ART delivery cost was $628 ppy at steady state. Models using local salaries and only core laboratory tests estimated costs of $529/$445 ppy (+/-VL testing, respectively). Models with lower salaries, lowest ART prices, and optimized healthcare worker schedules reduced costs by $100–200 ppy. Costs in a maximally efficient scale-up model were $320/$236 ppy (+/- VL testing). This included $39 for personnel, $106 for ART, $130/$46 for laboratory tests, and $46 for administrative/other costs. A key limitation of this study is its derivation and extrapolation of costs from one large rural treatment program of high CD4+ count individuals.ConclusionsIn a Ugandan HIV clinic, ART delivery costs—including VL testing—for individuals with CD4>350 were similar to estimates from high-efficiency programs. In higher efficiency scale-up models, costs were substantially lower. These favorable costs may be achieved because high CD4+ count patients are often asymptomatic, facilitating more efficient streamlined ART delivery. Our work provides a framework for calculating costs of efficient ART scale-up models using accessible data from specific programs and regions.

Introduction Loss-to-follow-up among women living with HIV (WLWHIV) may lead to unfavorable outcomes for both mother and exposed infant. This study traced WLWHIV disengaged from care and their infants and compared their outcomes with those retained in care. Methods The study included WLWHIV who initiated ART during pregnancy at six public clinics in Uganda. A woman was defined as disengaged (DW) if she had not attended her 6-week post-partum visit by 10 weeks after her estimated date of delivery. DW were matched with retained women (RW) by age and duration on ART. Nurse counselors traced all selected DW via telephone and community visits to assess vital status, infant HIV sero-status and maternal HIV viral load through blood draws. Results Between July 2017 and July 2018, 734 women (359 DW and 375 RW) were identified for the study. Tracing was attempted on 349 DW and 160 (44.6%) were successfully located and enrolled in the study. They were matched with 162 RW. Among DW, 52 (32.5%) transferred to another health facility. Very few DW, 39.0% were HIV virally suppressed (<1000 copies/ml) compared to RW 89.5%, P<0.001). Among 138 babies born to DW, 4.3% tested positive for HIV compared to 1.4% among babies born to RW (P = 0.163). Conclusion Pregnant and breastfeeding WLWHIV who disengage from care are difficult to find in urban environments. Many have detectable viral loads, leading to the potential for an increased risk of MTCT. Efforts to reduce disengagement from care are critical for the successful elimination of MTCT in resource-limited settings.

BackgroundWe investigated the association between CYP2B6 polymorphisms and efavirenz drug resistance among women living with HIV started on anti-retroviral therapy during pregnancy and with high viremia during post-partum.MethodsThis was a cross sectional study. Women between 6-12 weeks post-partum with viral load >1000 copies/ml were eligible. Sanger sequencing to detect resistant mutations and host genotyping were performed. We categorized efavirenz metabolizer genotype according to the AIDS clinical trials group algorithm as slow, intermediate and extensive; and compared efavirenz resistance among the metabolizer genotypes.Results Over a one-year period (July 2017-July 2018), three hundred and thirty two women were screened of whom 112 (34.8%) had viral load ≥1000 copies/ml of whom 62 had whole blood available for genotyping. Fifty-nine of these women had both viral resistance and human host genotypic results. We observed a higher frequency of efavirenz resistance among slow metabolizers (47% versus 34% in extensive and 28% in intermediate, metabolizers) but due to low numbers, this was not statistically significant. ConclusionsOur findings raise the possibility that CYP2B6 polymorphism may contribute to efavirenz drug resistance in women started on antiretroviral therapy during pregnancy and with high viremia in the post-partum period. If confirmed in a larger study, this would have important implications for all patients in sub-Saharan Africa receiving efavirenz and add further support to the changes in World Health Organization policy to switch away from efavirenz as first line antiretroviral therapy in countries with a high prevalence of CYP2B6 polymorphisms.

Background We investigated the association between CYP2B6 polymorphisms and efavirenz drug resistance among women living with HIV who started on antiretroviral therapy during pregnancy and with high viremia during post-partum. Methods This was a cross-sectional study of women with viral loads greater than 1000 copies/ml who were at least 6 weeks postpartum. Sanger sequencing was used to detect resistant mutations, as well as host genotyping, and efavirenz resistance was compared among the metabolizer genotypes. Results Over the course of one year (July 2017-July 2018), 322 women were screened, with 110 (34.2%) having viral loads of 1000 copies/ml and 62 having whole blood available for genotyping. Fifty-nine of these women had both viral resistance and human host genotypic results. Efavirenz resistance according to metabolizer genotype was; 47% in slow, 34% in extensive and 28% in intermediate metabolizers, but the difference was not statistically significant due to the small sample size. Conclusions There was no statistically significant difference in EFV resistance between EFV metabolizer genotypes in women who started antiretroviral therapy during pregnancy and had high viremia in the postpartum period. However, a numerical trend was discovered, which calls for confirmation in a large, well-designed, statistically powered study.