Search

Objectives: To provide accurate forecasts of the age distribution of people with HIV (PWH) in Kenya from 2025 to 2040., Design: Development of a compartmental model of HIV in Kenya, calibrated to historical estimates of HIV epidemiology., Methods: We forecasted changes in population size and age distribution of new HIV infections and PWH under the status quo and under scale-up of HIV services., Results: Without scale-up, new HIV infections were forecasted to fall from 34 000 (28 000-41 000) in 2,025 to 29 000 (15 000-57 000) in 2,040; the percentage of new infections occurring among persons over 30 increased from 33% (20-50%) to 40% (24-62%). The median age of PWH increased from 39 years (38-40) in 2025 to 43 years (39-46) in 2040, and the percentage of PWH over age 50 increased from 26% (23-29%) to 34% (26-43%). Under the full intervention scenario, new infections were forecasted to fall to 6,000 (3,000-12 000) in 2,040. The percentage of new infections occurring in people over age 30 increased to 52% (34-71%) in 2,040, and there was an additional shift in the age structure of PWH [forecasted median age of 46 (43-48) and 40% (33-47%) over age 50]., Conclusion: PWH in Kenya are forecasted to age over the next 15 years; improvements to the HIV care continuum are expected to contribute to the growing proportion of older PWH., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: We aimed to evaluate safety of 3 months weekly isoniazid-rifapentine (3HP) for tuberculosis (TB) prevention when co-administered with dolutegravir-based antiretroviral therapy (TLD), and compare viral suppression among those initiating TLD + 3HP vs. TLD alone., Design/methods: We analyzed data from an ongoing Phase 3 randomized trial comparing TB screening strategies among adults with CD4 + ≤350 cells/μl initiating routine antiretroviral therapy (ART) in Kampala, Uganda. TB screen-negative participants without contraindications are referred for self-administered 3HP. HIV viral load is routinely measured at 6 and 12 months. Here, we included TB-negative participants who initiated TLD with or without 3HP. We determined the number who discontinued 3HP due to drug toxicity. In addition, we assessed viral suppression at 6 and 12 months and used log-binomial regression to assess risk of viremia at 6 months for participants who initiated TLD + 3HP vs. TLD alone., Results: Of 453 participants initiating TLD (287 [63.4%] female, median age 30 years [interquartile range (IQR) 25-37], median pre-ART CD4 + cell count 188 cells/μl [IQR 86-271]), 163 (36.0%) initiated 3HP. Of these, 154 (94.5%) completed 3HP and one (0.6%) had treatment permanently discontinued due to a possible 3HP-related adverse event. At 6 months, for participants who received TLD + 3HP, risk of viremia >50 copies/ml was 1.51 [95% confidence interval (CI) 1.07-2.14] times that of participants who received TLD alone. There was no difference in viral suppression between those who received TLD + 3HP vs. TLD alone at 12 months., Conclusions: Co-administration of TLD + 3HP was well tolerated. However, those who received TLD + 3HP were less likely to achieve viral suppression within six-months compared to those who received TLD alone., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Early infant diagnosis of HIV (EID) improves child survival through earlier initiation of antiretroviral therapy (ART). In many settings, ART initiation is hindered by delays in testing performed in centralized labs. Point-of-care (PoC) platforms offer opportunities to improve the timeliness of ART initiation., Methods: We used a mathematical model to estimate the costs and performance of on-site PoC testing using three platforms (m-PIMA, GeneXpert IV, and GeneXpert Edge) compared with the standard of care (SoC). Primary outcomes included ART initiation within 60 days of sample collection, HIV-related mortality before ART initiation, and incremental cost-effectiveness ratios (ICERs)., Results: PoC testing significantly increased ART initiation within 60 days (from 19% with SoC to 82-84% with PoC) and decreased HIV-related mortality (from 23% with SoC to 5% with PoC). ART initiation and mortality were similar across PoC platforms. When only used for EID and with high coverage of prevention of mother-to-child transmission (PMTCT) programs, ICERs for PoC testing compared with the SoC ranged from $430 to $1097 per additional infant on ART within 60 days and from $1527 to $3888 per death averted. PoC-based testing was more cost-effective in settings with lower PMTCT coverage, greater delays in the SoC, and when PoC instruments could be integrated with other disease programs., Conclusion: Our findings illustrate that PoC platforms can dramatically improve the timeliness of EID and linkage to HIV care. The cost-effectiveness of PoC platforms depends on the cost of PoC testing, existing access to diagnostic testing, and the ability to integrate PoC testing with non-EID programs., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Tuberculosis preventive therapy for people living with HIV is effective, widely recommended, and increasingly prescribed, but completion rates are less than ideal, and adherence is not typically monitored. We sought to quantify adherence to isoniazid preventive therapy using a urine metabolite assay., Design: Two cross-sectional surveys., Setting: Rio de Janeiro, Brazil, 2008-2009; and Northwest Province, South Africa, 2018-2019., Participants: Two hundred and three Brazilian and 93 South African patients attending HIV clinics with active prescriptions for isoniazid preventive therapy MAIN OUTCOME MEASURES:: Self-reported isoniazid adherence, paired with semiquantitative measurement of urine isoniazid metabolites., Results: By self-report, 90% of patients [95% confidence interval (CI) 86-93%] reported having taken a dose of isoniazid on the day of enrollment or the preceding day, and 91% (95% CI 87-94%) reported missing an average of one dose or fewer per week. By urine testing, only 65% (95% CI 59-70%) of all patients, and 69% (95% CI 63-74%) of those who reported having taken isoniazid on the current or preceding day, had detectable urine metabolites (expected in 95% of patients at 24 h). Longer time since starting preventive therapy was independently associated with a negative urine test for isoniazid metabolites (adjusted prevalence ratio 1.11 per month of isoniazid, 95% CI 1.05-1.18)., Conclusion: Adherence to isoniazid preventive therapy among patients with HIV in Brazil and South Africa is inadequate, is overestimated by self-report, and declines with time on treatment. Shorter regimens for TB preventive therapy may improve adherence and completion, but adherence support for all patients may be necessary.

Objective: Both isoniazid preventive therapy (IPT) and antiretroviral therapy (ART) reduce tuberculosis risk in individuals living with HIV. We sought to estimate the broader, population-wide impact of providing a pragmatically implemented 12-month IPT regimen to ART recipients in a high-burden community., Design: Dynamic transmission model of a tuberculosis (TB)-HIV epidemic, calibrated to site-specific, historical epidemiologic and clinical trial data from Khayelitsha, South Africa., Methods: We projected the 5-year impact of delivering a 12-month IPT regimen community-wide to 85% of new ART initiators and 15%/year of those already on ART, accounting for IPT-attributable reductions in TB infection, progression, and transmission. We also evaluated scenarios of continuously-delivered IPT, ongoing ART scale-up, and lower tuberculosis incidence., Results: Under historical (early 2010) ART coverage, this ART-linked IPT intervention prevented one tuberculosis case per 18 [95% credible interval (CrI) 11-29] people treated. It lowered TB incidence by a projected 23% (95% CrI 14-30%) among people receiving ART, and by 5.2% (95% CrI 2.9-8.7%) in the total population. Continuous IPT reduced the number needed to treat to prevent one case of TB to 10 (95% CrI 7-16), though it required 74% more person-years of therapy (95% CrI 64-94%) to prevent one TB case, relative to 12-month therapy. Under expanding ART coverage, the tuberculosis incidence reduction achieved by 12-month IPT grew to 7.6% (95% CrI 4.3-12.6%). Effect sizes were similar in a simulated setting of lower TB incidence., Conclusions: IPT in conjunction with ART reduces tuberculosis incidence among those who receive therapy and has additional impact on tuberculosis transmission in the population.

Objective: To determine the effectiveness of efavirenz versus nevirapine in initial antiretroviral therapy regimens for adults in sub-Saharan Africa., Design: Observational cohort study., Methods: Study participants were 2817 HIV-infected, highly active antiretroviral therapy-naive adults who began nevirapine-based or efavirenz-based highly active antiretroviral therapy between January 1998 and September 2004 via a private-sector HIV/AIDS program in nine countries of southern Africa. The primary outcome was time to virologic failure (two measurements of viral loads >or=400 copies/ml). Secondary outcomes included all-cause mortality, time to viral load less than 400 copies/ml, pharmacy-claim adherence, and discontinuation of nevirapine or efavirenz without virologic failure., Results: The median follow-up period was 2.0 years (interquartile range 1.2-2.6). Patients started on nevirapine were significantly less likely than those started on efavirenz to achieve high adherence, whether defined as 100% (30.2 versus 38.1%, P < 0.002) or more than 90% (44.8 versus 49.4%, P < 0.02) pharmacy-claim adherence. In a multivariate analysis, patients on nevirapine had greater risk of virologic failure [hazard ratio (HR 1.52; 95% confidence interval (CI) 1.24-1.86)], death (2.17; 1.31-3.60), and regimen discontinuation (1.67; 1.32-2.11). Switching from nevirapine to efavirenz had no significant virologic effect, whereas switching from efavirenz to nevirapine resulted in significantly slower time to suppression (hazard ratio 0.58, 95% confidence interval 0.35-0.93) and faster time to failure (hazard ratio 3.92; 95% confidence interval 1.61-9.55) than remaining on efavirenz., Conclusion: In initial highly active antiretroviral therapy regimens, efavirenz was associated with superior virologic and clinical outcomes than nevirapine, suggesting that efavirenz might be the preferred nonnucleoside reverse transcriptase inhibitor in resource-limited settings. However, its higher cost and potential teratogenicity are important barriers to implementation.

Objective: To evaluate the cost-effectiveness and potential impact of expanded female condom distribution., Design: Cost-effectiveness analysis assessing HIV infections averted annually and incremental cost per HIV infection averted for country-wide distribution of the nitrile female condom (FC2) among sexually active individuals, 15-49 years, with access to publicly distributed condoms in Brazil and South Africa., Results: In Brazil, expansion of FC2 distribution to 10% of current male condom use would avert an estimated 604 (5-95th percentiles, 412-831) HIV infections at 20,683 US dollars (5-95th percentiles, 13,497-29,521) per infection averted. In South Africa, 9577 (5-95th percentiles, 6539-13,270) infections could be averted, at 985 US dollars (5-95th percentiles, 633-1412) per infection averted. The estimated cost of treating one HIV-infected individual is 21,970 US dollars (5-95th percentiles, 18,369-25,719) in Brazil and 1503 US dollars (5-95th percentiles, 1245-1769) in South Africa, indicating potential cost savings. The incremental cost of expanded distribution would be reduced to 8930 US dollars (5-95th percentiles, 5864-13,163) per infection averted in Brazil and 374 US dollars (5-95th percentiles, 237-553) in South Africa by acquiring FC2s through a global purchasing mechanism and increasing distribution threefold. Sensitivity analyses show model estimates to be most sensitive to the estimated prevalence of sexually transmitted infections, total sexual activity, and fraction of FC2s properly used., Conclusions: Expanded distribution of FC2 in Brazil and South Africa could avert substantial numbers of HIV infections at little or no net cost to donor or government agencies. FC2 may be a useful and cost-effective supplement to the male condom for preventing HIV.

Objective: To explore the potential impact of enhanced tuberculosis (TB) diagnostic techniques as a TB control strategy in an adult population with high HIV prevalence., Design: A compartmental difference-equation model of TB/HIV was developed using parameter estimates from the literature., Methods: The impact of five TB control interventions (rapid molecular testing, mycobacterial culture, community-wide and HIV-targeted active case finding, and highly active antiretroviral therapy) on TB incidence, prevalence, and mortality was modeled in a steady-state population with an HIV prevalence of 17% and annual TB incidence of 409 per 100 000. Sensitivity analyses assessed the influence of each model parameter on the interventions' mortality impact., Results: Enhanced diagnostic techniques (rapid molecular testing or culture) are each projected to reduce TB prevalence and mortality by 20% or more, an impact similar to that of active case-finding in 33% of the general community and greater than the effect achievable by case-finding or antiretroviral treatment efforts in HIV-positive patients alone. The projected impact of enhanced diagnostics on TB incidence (< 10% reduction) is smaller. The impact of TB diagnostics is sensitive to the quality of existing diagnostic standards and the level of access to diagnostic services, but is robust across a wide range of population parameters including HIV and TB incidence., Conclusions: Enhanced TB diagnostic techniques may have substantial impact on TB morbidity and mortality in HIV-endemic regions. As TB rates continue to increase in these areas, enhanced diagnostic techniques merit further consideration as TB control strategies.