Cumulative HIV Research Articles

The Potential Epidemiological Impact of COVID-19 on the HIV/AIDS Epidemic and the Cost-Effectiveness of Linked, Opt-Out HIV Testing: A Modeling Study in Six US Cities

Background: Widespread viral and serological testing for SARS-CoV-2 may present a unique opportunity to also test for HIV infection. We estimated the potential impact of adding linked, opt-out HIV testing alongside SARS-CoV-2 testing on HIV incidence and the cost-effectiveness of this strategy in six US cities.Methods: We calibrated a dynamic compartmental HIV transmission model to match the epidemiological characteristics of six US cities (Atlanta, Baltimore, Los Angeles, Miami, New York City, Seattle). For each city, we constructed three sets of scenarios: (1) sustained current levels of HIV-related treatment and prevention services (status quo); (2) temporary disruptions in health services and changes in sexual and injection risk behaviours at discrete levels between 0%-50%; and (3) linked HIV and SARS-CoV-2 testing offered to 10%-90% of the adult population in addition to scenario (2). We estimated cumulative HIV infections between 2020-2025, as well as incremental costs, quality-adjusted life years, and incremental cost-effectiveness ratios of linked HIV testing over 20 years.Findings: In the absence of linked, opt-out HIV testing, we estimated a best-case scenario (50% reduction in risk behaviours and no service disruptions) of 6,733 fewer HIV infections between 2020-2025 (16.5% decrease), and a worst-case scenario (no behavioural change and 50% reduction in service access) of 3,669 additional HIV infections (9.0% increase) across cities. If HIV testing could be offered to 10%-90% of the adult population, we estimated that a total of 576-7,225 (1.6%-17.2%) new infections could be averted. The intervention would require an initial investment of $20M-$218M across cities; however, the intervention would ultimately result in savings in health care costs in each city.Interpretation: Although COVID-19-related disruptions in HIV-related services may increase or decrease HIV incidence, a campaign in which HIV testing is linked with SARS-CoV-2 testing could substantially reduce HIV incidence and reduce direct and indirect health care costs attributable to HIV.Funding Statement: US NIH-NIDA Grant No. R01-DA041747Declaration of Interests: XZ, EK, SC, MP, WSA, CNB, CDR, DJF, BDLM, SHM, JM, LRM, BRS, SAS and BN declare no competing interests.

Comparison of 6-week PMTCT outcomes for HIV-exposed and HIV-unexposed infants in the era of lifelong ART: Results from an observational prospective cohort study.

Lifelong antiretroviral therapy (ART) reduces mother-to-child HIV transmission (MTCT) and improves maternal health. Data on the outcomes of HIV-exposed infants (HEI) compared to their unexposed counterparts in the era of universal ART is limited. We compared birth and 6-week outcomes among infants born to HIV-positive and HIV-negative women in Lesotho. 941 HIV-negative and 653 HIV-positive pregnant women were enrolled in an observational cohort to evaluate the effectiveness of prevention of mother-to-child HIV transmission (PMTCT) program after implementation of universal maternal ART in 14 health facilities. Pregnancy, delivery, birth, and 6-week data were collected through participant interviews and medical record review. DNA PCR testing for HEI was conducted within 2 weeks of birth and at around 6 weeks of age. Data were analysed to estimate the distribution of birth outcomes, mortality, HIV transmission and HIV-free survival at 6 weeks. HIV-positive women were older (mean age of 28.7 vs. 24.4 years) and presented for antenatal care earlier (mean gestational age of 23.0 weeks vs 25.3 weeks) than HIV-negative women. Prematurity was more frequent among HEI, 7.8% vs. 3.6%. There was no difference in rates of congenital anomalies between HEI (1.0%) and HIV-unexposed infants (HUI) (0.6%). Cumulative HIV transmission was 0.9% (N = 4/431) (95% CI:0.25-2.36) at birth and 1.0% (N = 6/583) (95% CI:0.38-2.23) at 6 weeks. Overall mortality, including stillbirths, was 5.2% and 6.0% by 6 weeks for HUI and HEI respectively. Among liveborn infants, 6-week HIV-free survival for HEI was 95.6% (95% CI:93.7-97.1) compared to 96.8% (95% CI:95.4-97.9) survival for HUI. Implementation of universal maternal ART lowers MTCT at 6 weeks of age with no differences in congenital anomalies or early mortality between HIV exposed Infants and HIV unexposed infants. However, HIV exposed infants continue to have high rates of prematurity despite improved maternal health on ART.

Temporal trends of population viral suppression in the context of Universal Test and Treat: the ANRS 12249 TasP trial in rural South Africa.

IntroductionThe universal test‐and‐treat (UTT) strategy aims to maximize population viral suppression (PVS), that is, the proportion of all people living with HIV (PLHIV) on antiretroviral treatment (ART) and virally suppressed, with the goal of reducing HIV transmission at the population level. This article explores the extent to which temporal changes in PVS explain the observed lack of association between universal treatment and cumulative HIV incidence seen in the ANRS 12249 TasP trial conducted in rural South Africa.MethodsThe TasP cluster‐randomized trial (2012 to 2016) implemented six‐monthly repeat home‐based HIV counselling and testing (RHBCT) and referral of PLHIV to local HIV clinics in 2 × 11 clusters opened sequentially. ART was initiated according to national guidelines in control clusters and regardless of CD4 count in intervention clusters. We measured residency status, HIV status, and HIV care status for each participant on a daily basis. PVS was computed per cluster among all resident PLHIV (≥16, including those not in care) at cluster opening and daily thereafter. We used a mixed linear model to explore time patterns in PVS, adjusting for sociodemographic changes at the cluster level.Results8563 PLHIV were followed. During the course of the trial, PVS increased significantly in both arms (23.5% to 46.2% in intervention, +22.8, p < 0.001; 26.0% to 44.6% in control, +18.6, p < 0.001). That increase was similar in both arms (p = 0.514). In the final adjusted model, PVS increase was most associated with increased RHBCT and the implementation of local trial clinics (measured by time since cluster opening). Contextual changes (measured by calendar time) also contributed slightly. The effect of universal ART (trial arm) was positive but limited.ConclusionsPVS was improved significantly but similarly in both trial arms, explaining partly the null effect observed in terms of cumulative HIV incidence between arms. The PVS gains due to changes in ART‐initiation guidelines alone are relatively small compared to gains obtained by strategies to maximize testing and linkage to care. The achievement of the 90‐90‐90 targets will not be met if the operational and implementational challenges limiting access to care and treatment, often context‐specific, are not properly addressed. Clinical trial number: NCT01509508 (clinicalTrials.gov)/DOH‐27‐0512‐3974 (South African National Clinical Trials Register).

Dapivirine vaginal ring for HIV prevention: modelling health outcomes, drug resistance and cost-effectiveness.

IntroductionA vaginal ring containing dapivirine is effective for HIV prevention as pre‐exposure prophylaxis (PrEP). We evaluated the potential epidemiological impact and cost‐effectiveness of dapivirine vaginal ring PrEP among 22‐ to 45‐year‐old women in KwaZulu‐Natal, South Africa.MethodsUsing mathematical modelling, we studied dapivirine vaginal ring PrEP implementation, either unprioritized, or prioritized based on HIV incidence (≥3% per year), age (22 to 29 years) or female sex worker status, alongside the implementation of voluntary medical male circumcision and antiretroviral therapy scaled‐up to UNAIDS Fast‐Track targets. Outcomes over the intervention (2019 to 2030) and lifetime horizons included cumulative HIV infections, life‐years lived, costs and cost‐effectiveness. We assessed the incremental cost‐effectiveness ratios against the revealed willingness to pay ($500) and the standard (2017 per capita gross domestic product; $6161) cost‐effectiveness thresholds for South Africa.ResultsCompared to a reference scenario without PrEP, implementation of dapivirine vaginal ring PrEP, assuming 56% effectiveness and covering 50% of 22 to 29‐year‐old or high‐incidence women, prevented 10% or 11% of infections by 2030 respectively. Equivalent, unprioritized coverage (30%) prevented fewer infections (7%), whereas 50% coverage of female sex workers had the least impact (4%). Drug resistance attributable to PrEP was modest (2% to 4% of people living with drug‐resistant HIV). Over the lifetime horizon, dapivirine PrEP implementation among female sex workers was cost‐saving, whereas incidence‐based PrEP cost $1898 per life‐year gained, relative to PrEP among female sex workers and $989 versus the reference scenario. In a scenario of 37% PrEP effectiveness, PrEP had less impact, but prioritization to female sex workers remained cost‐saving. In uncertainty analysis, female sex worker PrEP was consistently cost‐saving; and over the lifetime horizon, PrEP cost less than $6161 per life‐year gained in over 99% of simulations, whereas incidence‐ and age‐based PrEP cost below $500 per life‐year gained in 61% and 49% of simulations respectively. PrEP adherence and efficacy, and the effectiveness of antiretroviral therapy for HIV prevention, were the principal drivers of uncertainty in the cost‐effectiveness of PrEP.ConclusionsDapivirine vaginal ring PrEP would be cost‐saving in KwaZulu‐Natal if prioritized to female sex workers. PrEP's impact on HIV prevention would be increased, with potential affordability, if prioritized to women by age or incidence.

The Impact of "Churn" on Plasma HIV Burden Within a Population Under Care.

BackgroundCross-sectional reporting of viral suppression rates within a population underestimates the community viral load (VL) burden. Longitudinal approaches, while addressing cumulative effects, may still underestimate viral burden if “churn” (movement in and out of care) is not incorporated. We examined the impact of churn on the cumulative community HIV viral burden.MethodsAll HIV+ patients followed in 2016–2017 at the Southern Alberta Clinic (Calgary, Canada) were categorized as follows: (1) in continuous care, (2) newly diagnosed, (3) diagnosed elsewhere transferring care, (4) returning to care, (5) lost-to-follow-up, (6) moved care elsewhere, or (7) died. Patient days were classified by VL as suppressed (≤200copies/ml), unsuppressed (>200 copies/ml), and transmittable (>1500 copies/ml).ResultsOf 1934 patients, 78.4% had suppressed VL; 21.4% had ≥1 unsuppressed VL, and 18.7% ≥1 transmittable VL. Of 1 276 507 total patient days in care, 92.1% were spent suppressed, 7.9% unsuppressed (101 459 days), and 6.4% (81 847 days) transmittable. 88.7% of category 1 patients had suppressed VL, 11.3% ≥1 unsuppressed VL, and 8.9% ever a transmittable VL. Of category 2 patients, 90% became suppressed on treatment (mean – 62 days). 38.5% of category 3 patients presented with a transmittable VL. Category 4 and 5 patients combined had high rates of unsuppressed (54.5%) and transmittable (51.2%) VL and, while representing only 6.2% of all patients, they accounted for 37.1% of unsuppressed and 41.5% of all transmittable days.ConclusionFocus on VL of patients continuously in care misses those with unsuppressed and transmittable VL in a community. Patients moving in and out of care pose an underappreciated risk for HIV transmissions.

HIV prevalence, spatial distribution and risk factors for HIV infection in the Kenyan fishing communities of Lake Victoria.

IntroductionGlobal efforts to end HIV by 2030 focus on reducing and eventually eliminating new infections in priority populations. Identifying these populations and characterizing their vulnerability factors helps in guiding investment of scarce HIV prevention resources to achieve maximum impact. We sought to establish HIV prevalence, spatial distribution and risk factors for HIV infection in the Kenyan fishing communities of Lake Victoria.MethodsWe conducted a cross-sectional survey of 2637 people from all the 308 fish-landing beaches on the Kenyan shore of Lake Victoria. The number of participants enrolled at each beach were weighted based on the size of the beach, determined by the number of functional registered boats. We used simple random sampling to select those to be approached for study participation. Consenting participants were privately interviewed about their socio-economic and demographic characteristics and sexual behavior, and were invited for HIV test using the Kenya rapid HIV testing protocol. We used descriptive statistics and multivariate logistic and linear regression for analysis.ResultsWe found high HIV prevalence of 32% with significant differences between men (29%) and women (38%). Among men, having an HIV negative sexual partner, being circumcised, increasing number of condom protected sex acts in the preceding month, being younger and being a resident of Homa Bay, Kisumu, Siaya and Busia counties compared to Migori County reduced the risk of HIV infection. For women, being married, having more children with the current spouse, having an HIV negative sexual partner and being a resident of Busia compared to Migori County reduced the risk of HIV infection. We also found that longer distance from the beaches to the nearest public health facilities was associated with increasing cumulative HIV prevalence at the beaches.ConclusionFishing communities have high HIV prevalence and may greatly benefit from interventions such as wider ART coverage, couple HIV risk reduction counseling, PrEP use for HIV negative partner at substantial continuous risk, alongside other HIV prevention services that the Kenyan government is currently rolling out. This will additionally require adequate plans to synchronize the provision of these services with the population’s routine schedules for all these options to be reasonably accessible to them.

HIV Viremia During Pregnancy and Neurodevelopment of HIV-Exposed Uninfected Children in the Context of Universal Antiretroviral Therapy and Breastfeeding

Elevated HIV viral load (VL) in pregnancy has been linked to increased risk of mortality, immunologic abnormalities, infectious morbidity and restricted growth among HIV-exposed uninfected (HEU) children, but little is known about effects on child development. HIV-infected women initiating lifelong antiretroviral therapy (ART; tenofovir + emtricitabine + efavirenz) antenatally were followed from first antenatal visit through delivery and with their breastfed infants postpartum. Cognitive, motor and expressive language development (Bayley Scales of Infant and Toddler Development-Third Edition; delay defined as score <85) were assessed on a subset of HEU infants. HIV VL was measured at ART initiation, in third trimester and around delivery. Cumulative viremia in pregnancy was expressed as log10 VL copies × year/mL [viremia copy-years (VCY)]. Relationships between VCY and development were examined after adjusting for socioeconomic, behavioral and psychosocial confounders. Women (median pre-ART log10 VL 4.1, CD4 349 cells/mm) commonly reported adverse social circumstances (44% informal housing, 63% unemployed, 29% risky drinking). Among 214 infants (median age, 13 months; 53% male; 13% born <37 weeks' gestation), viremia predicted lower motor and expressive language, but not cognitive, scores in crude and adjusted analysis [per log10 VCY increase, αβ (95% confidence interval [CI]): motor, -2.94 (-5.77 to -0.11); language, -3.71 (-6.73 to -0.69) and cognitive -2.19 (-5.02 to 0.65)]. Increasing VCY also predicted higher relative odds of motor delay [adjusted odds ratio (aOR): 3.32; 95% CI: 1.36-8.14) and expressive language delay (aOR: 2.79; 95% CI: 1.57-4.94), but not cognitive delay (aOR: 1.68; 95% CI: 0.84-3.34). Cumulative maternal HIV viremia in pregnancy may have adverse implications for HEU child development.

Cumulative Human Immunodeficiency Viremia, Antiretroviral Therapy, and Incident Myocardial Infarction.

People living with HIV are at risk of increased myocardial infarction (MI). Cumulative HIV viral load (VL) has been proposed as a better measure of HIV inflammation than other measures of VL, like baseline VL, but its associations with MI are not known. The multisite Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort includes clinical data and centrally adjudicated MI with distinction between atheroembolic MI (type 1) and MI related to supply-demand mismatch (type 2). We examined CNICS participants who were not on antiretroviral therapy (ART) at enrollment. Cumulative VL (copy-days of virus) from 6 months after enrollment was estimated with a time-weighted sum using the trapezoidal rule. We modeled associations of cumulative and baseline VL with MI by type using marginal structural Cox models. We contrasted the 75% percentile of the VL distribution with the 25% percentile. Among 11,324 participants, 218 MIs occurred between 1996 and 2016. Higher cumulative VL was associated with risk of all MI (hazard ratio [HR] = 1.72; 95% confidence interval [CI] = 1.26, 2.36), type 1 MI (HR = 1.23; 95% CI = 0.78, 1.96), and type 2 MI (HR = 2.52; 95% CI = 1.74, 3.66). While off ART, cumulative VL had a stronger association with type 1 MI (HR = 2.13; 95% CI = 1.15, 3.94) than type 2 MI (HR = 1.25; 95% CI = 0.70, 2.25). Baseline VL was associated with all MI (HR = 1.60; 95% CI = 1.28, 2.01), type 1 MI (HR = 1.73; 95% CI = 1.26, 2.38), and type 2 MI (HR = 1.51; 95% CI = 1.10, 2.08). Higher cumulative and baseline VL is associated with all MI, with a particularly strong association between cumulative VL and type 2 MI.

Dynamics of the HIV outbreak and response in Scott County, IN, USA, 2011–15: a modelling study

In November, 2014, a cluster of HIV infections was detected among people who inject drugs in Scott County, IN, USA, with 215 HIV infections eventually attributed to the outbreak. This study examines whether earlier implementation of a public health response could have reduced the scale of the outbreak. In this modelling study, we derived weekly case data from the HIV outbreak in Scott County, IN, and on the uptake of HIV testing, treatment, and prevention services from publicly available reports from the US Centers for Disease Control and Prevention (CDC) and researchers from Indiana. Our primary objective was to determine if an earlier response to the outbreak could have had an effect on the number of people infected. We computed upper and lower bounds for cumulative HIV incidence by digitally extracting data from published images from a CDC study using Bio-Rad avidity incidence testing to estimate the recency of each transmission event. We constructed a generalisation of the susceptible-infectious-removed model to capture the transmission dynamics of the HIV outbreak. We computed non-parametric interval estimates of the number of individuals with an undiagnosed HIV infection, the case-finding rate per undiagnosed HIV infection, and model-based bounds for the HIV transmission rate throughout the epidemic. We used these models to assess the potential effect if the same intervention had begun at two key timepoints earlier than the actual date of the initiation of efforts to control the outbreak. The upper bound for undiagnosed HIV infections in Scott County peaked at 126 around Jan 10, 2015, over 2 months before the Governor of Indiana declared a public health emergency on March 26, 2015. Applying the observed case-finding rate scale-up to earlier intervention times suggests that an earlier public health response could have substantially reduced the total number of HIV infections (estimated to have been 183-184 infections by Aug 11, 2015). Initiation of a response on Jan 1, 2013, could have suppressed the number of infections to 56 or fewer, averting at least 127 infections; whereas an intervention on April 1, 2011, could have reduced the number of infections to ten or fewer, averting at least 173 infections. Early and robust surveillance efforts and case finding alone could reduce nascent epidemics. Ensuring access to HIV services and harm-reduction interventions could further reduce the likelihood of outbreaks, and substantially mitigate their severity and scope. US National Institute on Drug Abuse, US National Institutes of Mental Health, US National Institutes of Health Big Data to Knowledge programme, and the US National Institutes of Health.

Cumulative plasma HIV burden disparities among adults in HIV care: implications for HIV transmission in the era of treatment as prevention.

To characterize disparities in cumulative plasma HIV burden in a sample of adults accessing HIV care in San Francisco, California. Observational cohort and supplemental HIV surveillance data. Data from the San Francisco Medical Monitoring Project 2012-2014 cycles and HIV surveillance data were used to create an analytic cohort followed for 2 years. Matched HIV viral load test results from HIV surveillance were used to create five viral outcome measures: any unsuppressed viral load (>200 copies/ml), any transmittable viral load (>1500 copies/ml), person-time spent unsuppressed, person-time spent transmittable, and 2-year viremia copy-years, a measure of cumulative plasma HIV burden. Rao-Scott chi-squares and analysis of variance examined differences in durable suppression and mean percentage time spent unsuppressed and transmittable. Weighted linear regression was used to describe differences in cumulative HIV burden. Adults receiving HIV care spent approximately 12% of the 2-year time period with an unsuppressed viral load and approximately 7% of the time at a transmittable viral level. Factors independently associated with higher cumulative HIV viremia in an adjusted model included trans women identity, younger age, lower CD4 cell count, and a history of homelessness, incarceration, not taking ART, and nonadherence to ART. Although 95% of the cohort of adults in HIV care in San Francisco self-reported ART use during MMP interview, they spent on average almost 1 month per year at a transmittable viral level. We identified characteristics of those who were more likely to have higher viral burden, highlighting priorities for resource allocation to reduce onward HIV transmission.

Brief Report: Cutaneous Melanoma Risk Among People With HIV in the United States and Canada.

Cutaneous melanoma incidence may be modestly elevated in people with HIV (PWH) vs. people without HIV. However, little is known about the relationship of immunosuppression, HIV replication, and antiretroviral therapy (ART) with melanoma risk. PWH of white race in the North American AIDS Cohort Collaboration on Research and Design were included. A standardized incidence ratio was calculated comparing risk with the white general population, standardizing by age, sex, and calendar period. Associations between melanoma incidence and current, lagged, and cumulative measures of CD4 count, HIV RNA level, and ART use were estimated with Cox regression, adjusting for established risk factors such as age and annual residential ultraviolet B (UVB) exposure. Eighty melanomas were diagnosed among 33,934 white PWH (incidence = 40.75 per 100,000 person-years). Incidence was not elevated compared with the general population [standardized incidence ratio = 1.15, 95% confidence interval (95% CI) = 0.91 to 1.43]. Higher melanoma incidence was associated with older age [adjusted hazard ratio (aHR) per decade increase = 1.50, 95% CI = 1.20 to 1.89] and higher UVB exposure (aHR for exposure ≥35 vs. <35 mW/m = 1.62, 95% CI = 0.99 to 2.65). Current, lagged, and cumulative CD4 and HIV RNA were not associated with melanoma incidence. Melanoma incidence was higher among people ART-treated for a larger proportion of time in the previous 720 days (aHR per 10% increase = 1.16, 95% CI = 1.03 to 1.30). These results suggest that HIV-induced immune dysfunction does not influence melanoma development. The association between ART and melanoma risk may be due to increased skin surveillance among PWH engaged in clinical care. Associations with age and UVB confirmed those established in the general population.

Impact of Improved HIV Care and Treatment on PrEP Effectiveness in the United States, 2016-2020.

The effect of improving diagnosis, care, and treatment of persons living with HIV (PLWH) on pre-exposure prophylaxis (PrEP) effectiveness in the United States has not been well established. We used a dynamic, compartmental model that simulates the sexually active US population. We investigated the change in cumulative HIV incidence from 2016 to 2020 for 3 HIV care-continuum levels and the marginal benefit of PrEP compared with each. We also explored the marginal benefit of PrEP for individual risk groups, and as PrEP adherence, coverage and dropout rates varied. Delivering PrEP in 2016 to persons at high risk of acquiring HIV resulted in an 18.1% reduction in new HIV infections from 2016 to 2020 under current care-continuum levels. Achieving HIV national goals of 90% of PLWH with diagnosed infection, 85% of newly diagnosed PLWH linked to care at diagnosis, and 80% of diagnosed PLWH virally suppressed reduced cumulative incidence by 34.4%. Delivery of PrEP in addition to this scenario resulted in a marginal benefit of 11.1% additional infections prevented. When national goals were reached, PrEP prevented an additional 15.2% cases among men who have sex with men, 3.9% among heterosexuals, and 3.8% among persons who inject drugs. The marginal benefit of PrEP was larger when current HIV-care-continuum percentages were maintained but continued to be substantial even when national care goals were met. The high-risk men who have sex with men population was the chief beneficiary of PrEP.

Clinical Benefits and Cost-Effectiveness of Laboratory Monitoring Strategies to Guide Antiretroviral Treatment Switching in India.

Current Indian guidelines recommend twice-annual CD4 testing to monitor first-line antiretroviral therapy (ART), with a plasma HIV RNA test to confirm failure if CD4 declines, which would prompt a switch to second-line ART. We used a mathematical model to assess the clinical benefits and cost-effectiveness of alternative laboratory monitoring strategies in India. We simulated a cohort of HIV-infected patients initiating first-line ART and compared 11 strategies with combinations of CD4 and HIV RNA testing at varying frequencies. We included adaptive strategies that reduce the frequency of tests after 1 year from 6 to 12 months for virologically suppressed patients. We projected life expectancy, time on failed first-line ART, cumulative 10-year HIV transmissions, lifetime cost (2014 US dollars), and incremental cost-effectiveness ratios (ICERs). We defined strategies as cost-effective if their ICER was <1 × the Indian per capita gross domestic product (GDP, $1,600). We found that the current Indian guidelines resulted in a per person life expectancy (from mean age 37) of 150.2 months and a per person cost of $2,680. Adding annual HIV RNA testing increased survival by ∼8 months; adaptive strategies were less expensive than similar nonadaptive strategies with similar life expectancy. The most effective strategy with an ICER <1 × GDP was the adaptive HIV RNA strategy (ICER $840/year). Cumulative 10-year transmissions decreased from 27.2/1,000 person-years with standard-of-care to 20.9/1,000 person-years with adaptive HIV RNA testing. In India, routine HIV RNA monitoring of patients on first-line ART would increase life expectancy, decrease transmissions, be cost-effective, and should be implemented.

How should HIV resources be allocated? Lessons learnt from applying Optima HIV in 23 countries.

IntroductionWith limited funds available, meeting global health targets requires countries to both mobilize and prioritize their health spending. Within this context, countries have recognized the importance of allocating funds for HIV as efficiently as possible to maximize impact. Over the past six years, the governments of 23 countries in Africa, Asia, Eastern Europe and Latin America have used the Optima HIV tool to estimate the optimal allocation of HIV resources.MethodsEach study commenced with a request by the national government for technical assistance in conducting an HIV allocative efficiency study using Optima HIV. Each study team validated the required data, calibrated the Optima HIV epidemic model to produce HIV epidemic projections, agreed on cost functions for interventions, and used the model to calculate the optimal allocation of available funds to best address national strategic plan targets. From a review and analysis of these 23 country studies, we extract common themes around the optimal allocation of HIV funding in different epidemiological contexts.Results and discussionThe optimal distribution of HIV resources depends on the amount of funding available and the characteristics of each country's epidemic, response and targets. Universally, the modelling results indicated that scaling up treatment coverage is an efficient use of resources. There is scope for efficiency gains by targeting the HIV response towards the populations and geographical regions where HIV incidence is highest. Across a range of countries, the model results indicate that a more efficient allocation of HIV resources could reduce cumulative new HIV infections by an average of 18% over the years to 2020 and 25% over the years to 2030, along with an approximately 25% reduction in deaths for both timelines. However, in most countries this would still not be sufficient to meet the targets of the national strategic plan, with modelling results indicating that budget increases of up to 185% would be required.ConclusionsGreater epidemiological impact would be possible through better targeting of existing resources, but additional resources would still be required to meet targets. Allocative efficiency models have proven valuable in improving the HIV planning and budgeting process.

The impact of pre-exposure prophylaxis (PrEP) and screening on the dynamics of HIV

We analyse the impact of pre-exposure prophylaxis (PrEP) and screening effects on HIV dynamics in infected patients. Our model incorporates condom use, the number of sexual partners, and treatment for HIV. Numerical simulations are performed and the model is fitted to data on the cumulative HIV and AIDS cases in Portugal. Moreover, critical epidemiological parameters are also varied. Inferences are made concerning the epidemiological consequences of the model’s predictions on public HIV/AIDS planning. The order of the fractional derivative is suggested to have a powerful role in the drama of HIV epidemics. • A non-integer order model is derived to assess the impact of PrEP and HCT on the dynamics of HIV infection. • The screening efficacy, rather than the screening rate, provides better outcomes, with respect to HIV transmission. • Fractional models may be powerful tools to analyze HIV dynamics. • Biologically, non-integer order derivatives may help distinguish patients’ sexual behaviours.

The Cost-Effectiveness of Human Immunodeficiency Virus Testing and Treatment Engagement Initiatives in British Columbia, Canada: 2011-2013.

Recognition of the secondary preventive benefits of antiretroviral therapy (ART) has mobilized global efforts to "seek, test, treat, and retain" people living with human immunodeficiency virus [HIV]/AIDS (PLHIV) in HIV care. We aimed to determine the cost-effectiveness of a set of HIV testing and treatment engagement interventions initiated in British Columbia, Canada, in 2011-2013. Using a previously validated dynamic HIV transmission model, linked individual-level health administrative data for PLHIV, and aggregate-level HIV testing data, we estimated the cost-effectiveness of primary care testing (hospital, emergency department [ED], outpatient), ART initiation, and ART retention initiatives vs a counterfactual scenario that approximated the status quo. HIV incidence, mortality, costs (in 2015$CDN), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios were estimated. Analyses were executed over 5- to 25-year time horizons from a government-payer perspective. ED testing was the best value at $30216 per QALY gained and had the greatest impact on incidence and mortality among PLHIV, while ART initiation provided the greatest QALY gains. The ART retention initiative was not cost-effective. Delivered in combination at the observed scale and sustained throughout the study period, we estimated a 12.8% reduction in cumulative HIV incidence and a 4.7% reduction in deaths among PLHIV at $55258 per QALY gained. Results were most sensitive to uncertainty in the number of undiagnosed PLHIV. HIV testing and ART initiation interventions were cost-effective, while the ART retention intervention was not. Developing strategies to reengage PLHIV lost to care is a priority moving forward.

Information Communication Technology (ICT) use among PLHIV in China: A promising but underutilized venue for HIV prevention and care

In this paper, we report the use of information and communication technology (ICT) among people living with HIV (PLHIV) in Guangxi, China. A total 2987 participants were recruited from 12 sites with the highest number of cumulative HIV incidence, including 2 cities and 10 counties. A questionnaire survey was conducted to collect data on the participants’ social demographic characteristics, clinical outcomes, infections and coinfections, pattern of ICT use, and use and intention of using ICT in HIV and AIDS management. The data was analyzed using SPSS, version 24. The results showed 78.7% (n=2347) never used a computer, 86.9% (n=2587) had a cellphone, 32.7% (n=207) owned an email account, and 85.4% (n=544) owned a social media account. Less than half of the participants reported ever using ICTs for HIV management. Only 26.2% (n=266) were willing to join a web-based HIV prevention program. Findings of this study suggest that there was an imbalance in the participants’ ICT device ownership and choices of media platform. Social media appeared to be a potential platform for health intervention among this group. There was a low penetration of computer use among rural participants and a large disparity between the urban and rural participants, which indicated a need to expand the current infrastructure related to ICTs and increase people’s health literacy. Future research also needs to pay attention to security and trustworthiness of the intervention program to better promote ICTs as an efficient and reliable platform for HIV prevention and care.

Expanded antiretroviral treatment, sexual networks, and condom use: Treatment as prevention unlikely to succeed without partner reduction among men who have sex with men in China.

BackgroundTo project the impact of partner reduction on preventing new HIV infections among men who have sex with men (MSM) under varying conditions of enhanced HIV testing and treatment (T&T) and condom use in Beijing, China.Methods and findingsA complex network model was fitted to predict the number of new HIV infections averted from 2014 to 2023 under four scenarios of sexual behavior risk reduction (S)—S1: Male sexual partners decrease (reduced by a random value m from 1–50) while condom use increases (risk constant p is a random value between 0.2 and 1]); S2: Both sexual partners and condom use decrease (m 1, 50; p 1, 1.8); S3: Sexual partners reduce (m 1, 10) while condom use increases or decreases (p 0.2, 1.8); S4: Only MSM with ≥100 male sexual partners reduce their partners (m 1, 50) while condom use increases (p 0.2, 1).HIV prevalence will reach 23.2% by 2023 among Beijing MSM if T&T remains at the 2013 level. The three most influential factors are: T&T coverage; partner reduction (m); and the background risk (p). Under scenarios 1–4 of sexual behavioral changes with enhanced T&T interventions, the cumulative HIV new infections prevented over the 10 years will be 46.8% for S1 (interquartile range [IQR] 32.4%, 60.1%); 29.7% for S2 (IQR 18.0%, 41.4%), 23.2% for S3 (IQR 12.2%, 37.0%) and 11.6% for S4 (IQR 4.0%, 26.6%), respectively. The reproduction number R0 could drop below 1 if there were a substantial reduction of male sexual partners and/or expanded condom use.ConclusionPartner reduction is a vital factor within HIV combination interventions to reduce HIV incidence among Beijing MSM, with substantial additional benefits derived from condom use. T&T without substantial partner reduction and increased condom use is less promising unless its implementation were extremely (and improbably) efficient.

Using a network-based approach and targeted maximum likelihood estimation to evaluate the effect of adding pre-exposure prophylaxis to an ongoing test-and-treat trial.

Several cluster-randomized trials are underway to investigate the implementation and effectiveness of a universal test-and-treat strategy on the HIV epidemic in sub-Saharan Africa. We consider nesting studies of pre-exposure prophylaxis within these trials. Pre-exposure prophylaxis is a general strategy where high-risk HIV- persons take antiretrovirals daily to reduce their risk of infection from exposure to HIV. We address how to target pre-exposure prophylaxis to high-risk groups and how to maximize power to detect the individual and combined effects of universal test-and-treat and pre-exposure prophylaxis strategies. We simulated 1000 trials, each consisting of 32 villages with 200 individuals per village. At baseline, we randomized the universal test-and-treat strategy. Then, after 3 years of follow-up, we considered four strategies for targeting pre-exposure prophylaxis: (1) all HIV- individuals who self-identify as high risk, (2) all HIV- individuals who are identified by their HIV+ partner (serodiscordant couples), (3) highly connected HIV- individuals, and (4) the HIV- contacts of a newly diagnosed HIV+ individual (a ring-based strategy). We explored two possible trial designs, and all villages were followed for a total of 7 years. For each village in a trial, we used a stochastic block model to generate bipartite (male-female) networks and simulated an agent-based epidemic process on these networks. We estimated the individual and combined intervention effects with a novel targeted maximum likelihood estimator, which used cross-validation to data-adaptively select from a pre-specified library the candidate estimator that maximized the efficiency of the analysis. The universal test-and-treat strategy reduced the 3-year cumulative HIV incidence by 4.0% on average. The impact of each pre-exposure prophylaxis strategy on the 4-year cumulative HIV incidence varied by the coverage of the universal test-and-treat strategy with lower coverage resulting in a larger impact of pre-exposure prophylaxis. Offering pre-exposure prophylaxis to serodiscordant couples resulted in the largest reductions in HIV incidence (2% reduction), and the ring-based strategy had little impact (0% reduction). The joint effect was larger than either individual effect with reductions in the 7-year incidence ranging from 4.5% to 8.8%. Targeted maximum likelihood estimation, data-adaptively adjusting for baseline covariates, substantially improved power over the unadjusted analysis, while maintaining nominal confidence interval coverage. Our simulation study suggests that nesting a pre-exposure prophylaxis study within an ongoing trial can lead to combined intervention effects greater than those of universal test-and-treat alone and can provide information about the efficacy of pre-exposure prophylaxis in the presence of high coverage of treatment for HIV+ persons.

Substance Use and Psychosocial Status among People Living with HIV/AIDS Who Encountered HIV Stigma in China: Stratified Analyses by Socio-Economic Status.

This study examined whether the impact of HIV stigma on psychosocial status and substance use among people living with HIV/AIDS (PLWHA) differed by their socio-economic status (SES) in a Chinese setting. A total of 2,987 PLWHA were recruited from 12 sites with the highest number of cumulative HIV incidence in Guangxi, China. Participants were asked to provide information regarding their psychosocial status (e.g., depression, anxiety), history of substance use (e.g., tobacco, alcohol and drug) and SES (e.g., education, monthly income, residence type, and job category). By employing stratified multivariate regression analyses, we assessed stratum-specific impacts of HIV stigma on PLWHA’s psychosocial status and behaviors of substance use based upon participants’ SES. The impact of HIV stigma differed significantly on psychosocial status across SES gradients. Psychosocial status among people with higher education was more sensitive to HIV stigma compared with PLWHA who were less educated. The odds of substance use behaviors were higher among people with better monthly income than their low-income peers. Our study is the first paper to document the paucity of SES stratified analyses between HIV stigma and psychosocial status and substance use among PLWHA in China. We call for tailored intervention programs to target PLWHA with different backgrounds and characteristics in order to help them to better manage their seropositivity.