Roger Ying

Systematic review and meta-analysis of community and facility-based HIV testing to address linkage to care gaps in sub-Saharan Africa

HIV testing and counselling is the first crucial step for linkage to HIV treatment and prevention. However, despite high HIV burden in sub-Saharan Africa, testing coverage is low, particularly among young adults and men. Community-based HIV testing and counselling (testing outside of health facilities) has the potential to reduce coverage gaps, but the relative impact of different modalities is not well assessed. We conducted a systematic review of HIV testing modalities, characterizing community (home, mobile, index, key populations, campaign, workplace and self-testing) and facility approaches by population reached, HIV positivity, CD4 count at diagnosis and linkage. Of 2,520 abstracts screened, 126 met eligibility criteria. Community HIV testing and counselling had high coverage and uptake and identified HIV-positive people at higher CD4 counts than facility testing. Mobile HIV testing reached the highest proportion of men of all modalities examined (50%, 95% confidence interval (CI) = 47–54%) and home with self-testing reached the highest proportion of young adults (66%, 95% CI = 65–67%). Few studies evaluated HIV testing for key populations (commercial sex workers and men who have sex with men), but these interventions yielded high HIV positivity (38%, 95% CI = 19–62%) combined with the highest proportion of first-time testers (78%, 95% CI = 63–88%), indicating service gaps. Community testing with facilitated linkage (for example, counsellor follow-up to support linkage) achieved high linkage to care (95%, 95% CI = 87–98%) and antiretroviral initiation (75%, 95% CI = 68–82%). Expanding home and mobile testing, self-testing and outreach to key populations with facilitated linkage can increase the proportion of men, young adults and high-risk individuals linked to HIV treatment and prevention, and decrease HIV burden.This article has not been written or reviewed by Nature editors. Nature accepts no responsibility for the accuracy of the information provided.

Cost-effectiveness of pre-exposure prophylaxis targeted to high-risk serodiscordant couples as a bridge to sustained ART use in Kampala, Uganda

Despite scale‐up of antiretroviral therapy (ART) for treating HIV‐positive persons, HIV incidence remains elevated among those at high risk such as persons in serodiscordant partnerships. Antiretrovirals taken by HIV‐negative persons as pre‐exposure prophylaxis (PrEP) has the potential to avert infections in individuals in serodiscordant partnerships. Evaluating the cost‐effectiveness of implementing time‐limited PrEP as a short‐term bridge during the first six months of ART for the HIV‐positive partner to prevent HIV transmission compared to increasing ART coverage is crucial to informing policy‐makers considering PrEP implementation.

Home testing and counselling to reduce HIV incidence in a generalised epidemic setting: a mathematical modelling analysis

Summary Background Home HIV testing and counseling (HTC) achieves high levels of HIV testing and linkage to care. Periodic home HTC, particularly targeted to those with high HIV viral load, may facilitate expanding antiretroviral therapy (ART) coverage. We used a mathematical model to assess the impact of periodic home HTC programs on HIV incidence in KwaZulu-Natal, South Africa. Methods We developed a dynamic HIV transmission model with parameters, primary cost data, and measures of viral suppression collected from a prospective study of home HTC in KwaZulu-Natal. We assumed five-yearly home HTC with ART initiation for persons with CD4≤350 cells/µL. For individuals with CD4>350 cells/µL, we compared increasing ART coverage for those who have CD4 counts 350–500 cells/µL with those who have viral loads >10,000 copies/mL. Findings Maintaining the current level of 36% viral suppression among HIV-positive persons, HIV incidence decreases by 34% over 10 years. Five-yearly home HTC and linkage to care with ART initiation at CD4≤350 cells/µL reduces HIV incidence by 57% over 10 years. Expanding ART to persons with CD4>350 cells/µL who also have VL>10,000 copies/mL decreases HIV incidence by 68%, and was the most cost-effective strategy for preventing HIV infections at

CD4 Cell Count: Declining Value for Antiretroviral Therapy Eligibility

2,960 per infection averted. Expanding ART eligibility to persons with CD4 350–500 cells/µL is cost-effective at

Use of HIV viral-load suppression to estimate the effect of community-wide home-based HIV counselling and testing and linkage to antiretroviral therapy on HIV incidence in South Africa: a mathematical modelling analysis

900 per QALY gained. Following health economic guidelines, expanding ART use to those who have VL>10,000 copies/mL among those with CD4>350 cells/µL was cost-effective to reduce HIV-related morbidity. Interpretation In KwaZulu-Natal, five-yearly province-wide home HTC can cost-effectively increase ART coverage and reduce HIV burden. ART initiation criteria based on VL>10,000 copies/mL for those with CD4>350 cells/µL is also an efficient strategy for HIV prevention.

Estimating PMTCT's Impact on Heterosexual HIV Transmission: A Mathematical Modeling Analysis

Antiretroviral therapy (ART) policy for people living with human immunodeficiency virus (HIV) has historically been based on clinical indications, such as opportunistic infections and CD4 cell counts. Studies suggest that CD4 counts early in HIV infection do not predict relevant public health outcomes such as disease progression, mortality, and HIV transmission in people living with HIV. CD4 counts also vary widely within individuals and among populations, leading to imprecise measurements and arbitrary ART initiation. To capture the clinical and preventive benefits of treatment, the global HIV response now focuses on increasing HIV diagnosis and ART coverage. CD4 counts for ART initiation were necessary when medications were expensive and had severe side effects, and when the impact of early ART initiation was unclear. However, current evidence suggests that although CD4 counts may still play a role in guiding clinical care to start prophylaxis for opportunistic infections, CD4 counts should cease to be required for ART initiation.

Modeling HIV disease progression and transmission at population-level: The potential impact of modifying disease progression in HIV treatment programs

Abstract Background High coverage of HIV counselling and testing (HCT) through community campaigns, which link most HIV-positive people to care, has the potential to decrease HIV incidence if most eligible people initiate antiretroviral therapy (ART) and are virally suppressed. The aim of our analysis was to use transmission models of HIV to estimate the effect of home-based HCT on HIV incidence in South Africa. Methods We did an observational cohort study of community-wide home-based HCT in KwaZulu-Natal, South Africa, from September, 2011 to May, 2013. Resident adults within a geographically defined community were offered HCT. HIV-positive people received point-of-care CD4 cell count results, counselling about HIV and ART, referral for HIV care, and follow-up visits at months 1, 3, 6, 9, and 12. We assessed risk behaviour and adherence for HIV-positive people on ART. HIV viral load was measured among all HIV-positive people at baseline, 6 months, and 12 months. Using baseline HCT data and estimates from the literature, we developed a compartmental, deterministic model of HIV incidence in KwaZulu-Natal, incorporating sexual behaviour and ART use. The model population was stratified by sex, age, sexual activity, circumcision status, and condom use. We assumed that viral suppression on ART decreases HIV transmission by 90%, ART dropout was 5% annually, and the transmission probability in acute HIV was 26-fold higher than in chronic infection. Model output for HIV prevalence and incidence was validated with independent HIV survey data. We modelled the effect of home-based HCT every 5 years on HIV incidence at 5, 10, and 20 years. Findings Of 1296 adults, 1273 (98%) were tested for HIV, of whom 404 (32%) were positive. At baseline, 158 (39%) participants were on ART and 127 (32%) were eligible for ART according to national guidelines (CD4 count ≤350 cells per μL). The median CD4 cell count among ART-naive individuals was high (472 cells per μL). By month 6, 359 (88%) participants of the HIV-positive group identified at baseline had visited an HIV clinic, and by month 12, 111 had initiated ART. At month 12, HIV viral load was suppressed among 233 (58%) of all HIV-positive people and among 170 (71%) of HIV-positive people on ART (n=241). With use of the proportion of all HIV-positive participants with viral suppression to indicate ART coverage and adherence, modelling estimated that: HCT every 5 years with ART initiated at CD4 count of 350 cells per μL or less would decrease HIV incidence over 5, 10, and 20 years by 31·3%, 32·9%, and 33·1%, respectively; and ART initiation at the new WHO guideline level of CD4 count of 500 cells per μL or fewer would decrease incidence by 41·0%, 44·6%, and 45·3%, respectively. With each round of HCT (assuming ART initiation at CD4 count ≤350 cells per μL), the proportion of incident cases from acute infection increased from 26% to 31%, 37%, and 40% over 5, 10, and 20 years, respectively. Interpretation Achievable rates of HCT to ensure community-wide HIV testing and ART initiation at levels recommended by current South African guidelines could substantially decrease HIV incidence, if the majority of HIV-positive people achieve viral suppression. The effect will be limited by transmission from acutely infected, untreated individuals who are highly infectious. Funding We acknowledge the support of the NIH Directors Award, RC4 AI092552.

Assisted partner notification services are cost-effective for decreasing HIV burden in western Kenya: A mathematical modeling analysis

Introduction Prevention of mother-to-child HIV transmission (PMTCT) strategies include combined short-course antiretrovirals during pregnancy (Option A), triple-drug antiretroviral treament (ART) during pregnancy and breastfeeding (Option B), or lifelong ART (Option B+). The WHO also recommends ART for HIV treatment and prevention of sexual transmission of HIV. The impact of PMTCT strategies on prevention of sexual HIV transmission of HIV is not known. We estimated the population-level impact of PMTCT interventions on heterosexual HIV transmission in southwestern Uganda and KwaZulu-Natal, South Africa, two regions with different HIV prevalence and fertility rates. Materials and Methods We constructed and validated dynamic, stochastic, network-based HIV transmission models for each region. PMTCT Options A, B, and B+ were simulated over ten years under three scenarios: 1) current ART and PMTCT coverage, 2) current ART and high PMTCT coverage, and 3) high ART and PMTCT coverage. We compared adult HIV incidence after ten years of each intervention to Option A (and current ART) at current coverage. Results At current coverage, Options B and B+ reduced heterosexual HIV incidence by about 5% and 15%, respectively, in both countries. With current ART and high PMTCT coverage, Option B+ reduced HIV incidence by 35% in Uganda and 19% in South Africa, while Option B had smaller, but meaningful, reductions. The greatest reductions in HIV incidence were achieved with high ART and PMTCT coverage. In this scenario, all PMTCT strategies yielded similar results. Discussion Implementation of Options B/B+ reduces adult HIV incidence, with greater effect (relative to Option A at current levels) in Uganda than South Africa. These results are likely driven by Uganda’s higher fertility rates.

Estimating PMTCT's impact on heterosexual HIV transmission

INTRODUCTION Mathematical models that incorporate HIV disease progression dynamics can estimate the potential impact of strategies that delay HIV disease progression and reduce infectiousness for persons not on antiretroviral therapy (ART). Suppressive treatment of HIV-positive persons co-infected with herpes simplex virus-2 (HSV-2) with valacyclovir, an HSV-2 antiviral, can lower HIV viral load, but the impact of partially-suppressive valacyclovir relative to fully-suppressive ART on population HIV transmission has not been estimated. METHODS We modeled HIV disease progression as a function of changes in viral load and CD4 count over time among ART naïve persons. The disease progression Markov model was nested within a dynamic model of HIV transmission at population level. We assumed that valacyclovir reduced HIV viral load by 1.23 log copies/μL, and that persons treated with valacyclovir initiated ART more rapidly when their CD4 fell below 500 due to retention in HIV care. We estimated the potential impact of valacyclovir on onward transmission of HIV in three scenarios of different ART and valacyclovir population coverage. RESULTS The average duration of HIV infection was 9.5 years. The duration of disease before reaching CD4 200cells/μL was 2.53 years longer for females than males. Relative to a baseline of ART initiation at CD4≤500cells/μL, the valacyclovir scenario resulted in 167,000 fewer HIV infections over ten years, with an incremental cost-effectiveness ratio (ICER) of

Estimating PMTCT's impact on heterosexual HIV transmission: A mathematical modeling analysis - eScholarship

5276 per HIV infection averted. A Test and Treat scenario with 70% ART coverage and no valacyclovir resulted in 350,000 fewer HIV infections at an ICER of