SARS-CoV-2 incidence, testing rates, and severe COVID-19 outcomes among people with and without HIV.

To assess SARS-CoV-2 outcomes, we matched a municipal COVID-19 registry and clinic rosters from a municipal primary care network containing a large HIV clinic and assessed clinical outcomes by HIV status. The risk of severe COVID-19 was higher among people with HIV (PWH, adjusted relative risk = 1.84, 95% confidence interval = 1.05-3.25), while SARS-CoV-2 incidence was lower despite higher testing rates. SARS-CoV-2 vaccination campaigns should prioritize PWH to prevent severe COVID-19 disease given potentially higher risk.

SARS-CoV-2 seroprevalence, and IgG concentration and pseudovirus neutralising antibody titres after infection, compared by HIV status: a matched case-control observational study.

BACKGROUND: Most cohorts show similar or lower COVID-19 incidence among people living with HIV compared with the general population. However, incidence might be affected by lower testing rates among vulnerable populations. We aimed to compare SARS-CoV-2 IgG seroprevalence, disease severity, and neutralising antibody activity after infection among people with and without HIV receiving care in a county hospital system over a 3-month period. METHODS: In this matched case-control observational study, remnant serum samples were collected between Aug 1 and Oct 31, 2020, from all people living with HIV who underwent routine outpatient laboratory testing in a municipal health-care system (San Francisco General Hospital, CA, USA). Samples from people living with HIV were date of collection-matched (same day) and age-matched (±5 years) to samples from randomly selected adults (aged 18 years or older) without HIV receiving care for chronic conditions at the same hospital. We compared seroprevalence by HIV status via mixed-effects logistic regression models, accounting for the matched structure of the data (random effects for the matched group), adjusting for age, sex, race or ethnicity, and clinical factors (ie, history of cardiovascular or pulmonary disease, and type 2 diabetes). Severe COVID-19 was assessed in participants with past SARS-CoV-2 (IgG or PCR) infection by chart review and compared with multivariable mixed-effects logistic regression, adjusting for age and sex. SARS-CoV-2 IgG, neutralising antibody titres, and antibody avidity were measured in serum of participants with previous positive PCR tests and compared with multivariable mixed-effects models, adjusting for age, sex, and time since PCR-confirmed SARS-CoV-2 infection. FINDINGS: 1138 samples from 955 people living with HIV and 1118 samples from 1062 people without HIV were tested. SARS-CoV-2 IgG seroprevalence was 3·7% (95% CI 2·4 to 5·0) among people with HIV compared with 7·4% (5·7 to 9·2) among people without HIV (adjusted odds ratio 0·50, 95% CI 0·30 to 0·83). Among 31 people with HIV and 70 people without HIV who had evidence of past infection, the odds of severe COVID-19 were 5·52 (95% CI 1·01 to 64·48) times higher among people living with HIV. Adjusting for time since PCR-confirmed infection, SARS-CoV-2 IgG concentrations were lower (percentage change -53%, 95% CI -4 to -76), pseudovirus neutralising antibody titres were lower (-67%, -25 to -86), and avidity was similar (7%, -73 to 87) among people living with HIV compared with those without HIV. INTERPRETATION: Although fewer infections were detected by SARS-CoV-2 IgG testing among people living with HIV than among those without HIV, people with HIV had more cases of severe COVID-19. Among people living with HIV with past SARS-CoV-2 infection, lower IgG concentrations and pseudovirus neutralising antibody titres might reflect a diminished serological response to infection, and the similar avidity could be driven by similar time since infection. FUNDING: US National Institute of Allergy and Infectious Diseases, US National Institutes of Health.

Costs of integrating hypertension care into HIV care in rural East African clinics.

OBJECTIVE: Sub-Saharan Africa faces twin epidemics of HIV and noncommunicable diseases including hypertension. Integrating hypertension care into chronic HIV care is a global priority, but cost estimates are lacking. In the SEARCH Study, we performed population-level HIV/hypertension testing, and offered integrated streamlined chronic care. Here, we estimate costs for integrated hypertension/HIV care for HIV-positive individuals, and costs for hypertension care for HIV-negative individuals in the same clinics. DESIGN: Microcosting analysis of healthcare expenditures within Ugandan HIV clinics. METHODS: SEARCH (NCT: 01864603) conducted community health campaigns for diagnosis and linkage to care for both HIV and hypertension. HIV-positive patients received hypertension/HIV care jointly including blood pressure monitoring and medications; HIV-negative patients received hypertension care at the same clinics. Within 10 Ugandan study communities during 2015-2016, we estimated incremental annual per-patient hypertension care costs using micro-costing techniques, time-and-motion personnel studies, and administrative/clinical records review. RESULTS: Overall, 70 HIV-positive and 2355 HIV-negative participants received hypertension care. For HIV-positive participants, average incremental cost of hypertension care was $6.29 per person per year, a 2.1% marginal increase over prior estimates for HIV care alone. For HIV-negative participants, hypertension care cost $11.39 per person per year, a 3.8% marginal increase over HIV care costs. Key costs for HIV-positive patients included hypertension medications ($6.19 per patient per year; 98% of total) and laboratory testing ($0.10 per patient per year; 2%). Key costs for HIV-negative patients included medications ($5.09 per patient per year; 45%) and clinic staff salaries ($3.66 per patient per year; 32%). CONCLUSION: For only 2-4% estimated additional costs, hypertension care was added to HIV care, and also expanded to all HIV-negative patients in prototypic Ugandan clinics, demonstrating substantial synergy. Our results should encourage accelerated scale-up of hypertension care into existing clinics.

HIV incidence after pre-exposure prophylaxis initiation among women and men at elevated HIV risk: A population-based study in rural Kenya and Uganda.

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, but data are limited on HIV incidence among PrEP users in generalized epidemic settings, particularly outside of selected risk groups. We performed a population-based PrEP study in rural Kenya and Uganda and sought to evaluate both changes in HIV incidence and clinical and virologic outcomes following seroconversion on PrEP. METHODS AND FINDINGS: During population-level HIV testing of individuals ≥15 years in 16 communities in the Sustainable East Africa Research in Community Health (SEARCH) study (NCT01864603), we offered universal access to PrEP with enhanced counseling for persons at elevated HIV risk (based on serodifferent partnership, machine learning-based risk score, or self-identified HIV risk). We offered rapid or same-day PrEP initiation and flexible service delivery with follow-up visits at facilities or community-based sites at 4, 12, and every 12 weeks up to week 144. Among participants with incident HIV infection after PrEP initiation, we offered same-day antiretroviral therapy (ART) initiation and analyzed HIV RNA, tenofovir hair concentrations, drug resistance, and viral suppression (<1,000 c/ml based on available assays) after ART start. Using Poisson regression with cluster-robust standard errors, we compared HIV incidence among PrEP initiators to incidence among propensity score-matched recent historical controls (from the year before PrEP availability) in 8 of the 16 communities, adjusted for risk group. Among 74,541 individuals who tested negative for HIV, 15,632/74,541 (21%) were assessed to be at elevated HIV risk; 5,447/15,632 (35%) initiated PrEP (49% female; 29% 15-24 years; 19% in serodifferent partnerships), of whom 79% engaged in ≥1 follow-up visit and 61% self-reported PrEP adherence at ≥1 visit. Over 7,150 person-years of follow-up, HIV incidence was 0.35 per 100 person-years (95% confidence interval [CI] 0.22-0.49) among PrEP initiators. Among matched controls, HIV incidence was 0.92 per 100 person-years (95% CI 0.49-1.41), corresponding to 74% lower incidence among PrEP initiators compared to matched controls (adjusted incidence rate ratio [aIRR] 0.26, 95% CI 0.09-0.75; p = 0.013). Among women, HIV incidence was 76% lower among PrEP initiators versus matched controls (aIRR 0.24, 95% CI 0.07-0.79; p = 0.019); among men, HIV incidence was 40% lower, but not significantly so (aIRR 0.60, 95% CI 0.12-3.05; p = 0.54). Of 25 participants with incident HIV infection (68% women), 7/25 (28%) reported taking PrEP ≤30 days before HIV diagnosis, and 24/25 (96%) started ART. Of those with repeat HIV RNA after ART start, 18/19 (95%) had <1,000 c/ml. One participant with viral non-suppression was found to have transmitted viral resistance, as well as emtricitabine resistance possibly related to PrEP use. Limitations include the lack of contemporaneous controls to assess HIV incidence without PrEP and that plasma samples were not archived to assess for baseline acute infection. CONCLUSIONS: Population-level offer of PrEP with rapid start and flexible service delivery was associated with 74% lower HIV incidence among PrEP initiators compared to matched recent controls prior to PrEP availability. HIV infections were significantly lower among women who started PrEP. Universal HIV testing with linkage to treatment and prevention, including PrEP, is a promising approach to accelerate reductions in new infections in generalized epidemic settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT01864603.

The interplay between HIV and COVID-19: summary of the data and responses to date.

PURPOSE OF REVIEW: We examine the interplay between the HIV and COVID-19 epidemics, including the impact of HIV on COVID-19 susceptibility and severe disease, the effect of the COVID-19 epidemic on HIV prevention and treatment, and the influence of the HIV epidemic on responses to COVID-19. RECENT FINDINGS: Evidence to date does not suggest that people living with HIV (PLWH) have a markedly higher susceptibility to SARS-CoV-2 infection, with disparities in the social determinants of health and comorbidities likely having a greater influence. The majority of literature has not supported a higher risk for severe disease among PLWH in Europe and the United States, although a large, population-based study in South Africa reported a higher rate of death due to COVID-19. Higher rates of comorbidities associated with COVID-19 disease severity among PLWH is an urgent concern. COVID-19 is leading to decreased access to HIV prevention services and HIV testing, and worsening HIV treatment access and virologic suppression, which could lead to worsening HIV epidemic control. CONCLUSION: COVID-19 is threatening gains against the HIV epidemic, including the U.S. Ending the HIV Epidemic goals. The ongoing collision of these two global pandemics will continue to need both study and interventions to mitigate the effects of COVID-19 on HIV efforts worldwide.

Management and Outcomes of Critically-III Patients with COVID-19 Pneumonia at a Safety-net Hospital in San Francisco, a Region with Early Public Health Interventions: A Case Series.

Background: Following early implementation of public health measures, San Francisco has experienced a slow rise and a low peak level of coronavirus disease 2019 (COVID-19) cases and deaths. Methods and Findings: We included all patients with COVID-19 pneumonia admitted to the intensive care unit (ICU) at the safety net hospital for San Francisco through April 8, 2020. Each patient had ≥15 days of follow-up. Among 26 patients, the median age was 54 years (interquartile range, 43 to 62), 65% were men, and 77% were Latinx. Mechanical ventilation was initiated for 11 (42%) patients within 24 hours of ICU admission and 20 patients (77%) overall. The median duration of mechanical ventilation was 13.5 days (interquartile range, 5 to 20). Patients were managed with lung protective ventilation (tidal volume ≤8 ml/kg of ideal body weight and plateau pressure ≤30 cmH2O on 98% and 78% of ventilator days, respectively). Prone positioning was used for 13 of 20 (65%) ventilated patients for a median of 5 days (interquartile range, 2 to 10). Seventeen (65%) patients were discharged home, 1 (4%) was discharged to nursing home, 3 (12%) were discharged from the ICU, and 2 (8%) remain intubated in the ICU at the time of this report. Three (12%) patients have died. Conclusions: Good outcomes were achieved in critically ill patients with COVID-19 by using standard therapies for acute respiratory distress syndrome (ARDS) such as lung protective ventilation and prone positioning. Ensuring hospitals can deliver sustained high-quality and evidence-based critical care to patients with ARDS should remain a priority.

Uptake, engagement, and adherence to pre-exposure prophylaxis offered after population HIV testing in rural Kenya and Uganda: 72-week interim analysis of observational data from the SEARCH study.

BACKGROUND: Optimal strategies for pre-exposure prophylaxis (PrEP) engagement in generalised HIV epidemics are unknown. We aimed to assess PrEP uptake and engagement after population-level HIV testing and universal PrEP access to characterise gaps in the PrEP cascade in rural Kenya and Uganda. METHODS: We did a 72-week interim analysis of observational data from the ongoing SEARCH (Sustainable East Africa Research in Community Health) study. Following community sensitisation and PrEP education, we did HIV testing and offered PrEP at health fairs and facilities in 16 rural communities in western Kenya, eastern Uganda, and western Uganda. We provided enhanced PrEP counselling to individuals 15 years and older who were assessed as having an elevated HIV risk on the basis of serodifferent partnership or empirical risk score, or who otherwise self-identified as being at high risk but were not in serodifferent partnerships or identified by the risk score. PrEP follow-up visits were done at facilities, homes, or community locations. We assessed PrEP uptake within 90 days of HIV testing, programme engagement (follow-up visit attendance at week 4, week 12, and every 12 weeks thereafter), refills, self-reported adherence up to 72 weeks, and concentrations of tenofovir in hair samples from individuals reporting HIV risk and adherence during follow-up, and analysed factors associated with uptake and adherence. This study is registered with ClinicalTrials.gov, NCT01864603. FINDINGS: Between June 6, 2016, and June 23, 2017, 70 379 community residents 15 years or older who had not previously been diagnosed with HIV were tested during population-level HIV testing. Of these individuals, 69 121 tested HIV-negative, 12 935 of whom had elevated HIV risk (1353 [10%] serodifferent partnership, 6938 [54%] risk score, 4644 [36%] otherwise self-identified risk). 3489 (27%) initiated PrEP, 2865 (82%) of whom did so on the same day as HIV testing and 1733 (50%) of whom were men. PrEP uptake was lower among individuals aged 15-24 years (adjusted odds ratio 0·55, 95% CI 0·45-0·68) and mobile individuals (0·61, 0·41-0·91). At week 4, among 3466 individuals who initiated PrEP and did not withdraw or die before the first visit, 2215 (64%) were engaged in the programme, 1701 (49%) received medication refills, and 1388 (40%) self-reported adherence. At week 72, 1832 (56%) of 3274 were engaged, 1070 (33%) received a refill, and 900 (27%) self-reported adherence. Among participants reporting HIV risk at weeks 4-72, refills (89-93%) and self-reported adherence (70-76%) were high. Among sampled participants self-reporting adherence at week 24, the proportion with tenofovir concentrations in the hair reflecting at least four doses taken per week was 66%, and reflecting seven doses per week was 44%. Participants who stopped PrEP accepted HIV testing at 4274 (83%) of 5140 subsequent visits; half of these participants later restarted PrEP. 29 participants of 3489 who initiated PrEP had serious adverse events, including seven deaths. Five adverse events (all grade 3) were assessed as being possibly related to the study drug. INTERPRETATION: During population-level HIV testing, inclusive risk assessment (combining serodifferent partnership, an empirical risk score, and self-identification of HIV risk) was feasible and identified individuals who could benefit from PrEP. The biggest gap in the PrEP cascade was PrEP uptake, particularly for young and mobile individuals. Participants who initiated PrEP and had perceived HIV risk during follow-up reported taking PrEP, but one-third had drug concentrations consistent with poor adherence, highlighting the need for novel approaches and long-acting formulations as PrEP roll-out expands. FUNDING: National Institutes of Health, President's Emergency Plan for AIDS Relief, Bill & Melinda Gates Foundation, and Gilead Sciences.

The Influence of Social Networks on Antiretroviral Therapy Initiation Among HIV-Infected Antiretroviral Therapy-Naive Youth in Rural Kenya and Uganda.

BACKGROUND: HIV-infected youth in sub-Saharan Africa are less likely to initiate antiretroviral therapy (ART) than older adults. SETTING AND METHODS: Adult (≥15 years) residents enumerated during a census in 32 communities in rural Kenya and Uganda named social contacts in 5 domains: health, money, emotional support, food, and free time. Named contacts were matched to other enumerated residents to build social networks among 150,395 adults; 90% were tested for HIV at baseline. Among youth (15-24 years) who were ART naive at baseline (2013-2014), we evaluated whether having ≥1 network contact who was HIV infected predicted ART initiation within 3 years and modification of this association by age and strength of contact, using logistic regression with robust standard errors. RESULTS: Among 1120 HIV-infected youth who were ART naive at baseline, 805 remained alive and community residents after 3 years. Of these, 270 (33.5%) named at least one baseline HIV-infected contact; 70% (569/805) subsequently initiated ART. Youth with ≥1 HIV-infected same-age baseline contact were more likely to initiate ART [adjusted odds ratio (aOR), 2.95; 95% confidence interval (CI): 1.49 to 5.86] than those with no HIV-infected contact, particularly if the contact was a strong tie (named in >1 domain; aOR, 5.33; 95% CI: 3.34 to 8.52). When nonhousehold contacts were excluded, having an HIV-infected same age contact who was a strong tie remained associated with ART initiation (aOR, 2.81; 95% CI: 1.76 to 4.49). CONCLUSIONS: Interventions that increase and strengthen existing social connections to other HIV-infected peers at the time of HIV diagnosis may increase ART initiation among HIV-infected youth.

Hypertension control in integrated HIV and chronic disease clinics in Uganda in the SEARCH study.

BACKGROUND: There is an increasing burden of hypertension (HTN) across sub-Saharan Africa where HIV prevalence is the highest in the world, but current care models are inadequate to address the dual epidemics. HIV treatment infrastructure could be leveraged for the care of other chronic diseases, including HTN. However, little data exist on the effectiveness of integrated HIV and chronic disease care delivery systems on blood pressure control over time. METHODS: Population screening for HIV and HTN, among other diseases, was conducted in ten communities in rural Uganda as part of the SEARCH study (NCT01864603). Individuals with either HIV, HTN, or both were referred to an integrated chronic disease clinic. Based on Uganda treatment guidelines, follow-up visits were scheduled every 4 weeks when blood pressure was uncontrolled, and either every 3 months, or in the case of drug stock-outs more frequently, when blood pressure was controlled. We describe demographic and clinical variables among all patients and used multilevel mixed-effects logistic regression to evaluate predictors of HTN control. RESULTS: Following population screening (2013-2014) of 34,704 adults age ≥ 18 years, 4554 individuals with HTN alone or both HIV and HTN were referred to an integrated chronic disease clinic. Within 1 year 2038 participants with HTN linked to care and contributed 15,653 follow-up visits over 3 years. HTN was controlled at 15% of baseline visits and at 46% (95% CI: 44-48%) of post-baseline follow-up visits. Scheduled visit interval more frequent than clinical indication among patients with controlled HTN was associated with lower HTN control at the subsequent visit (aOR = 0.89; 95% CI 0.79-0.99). Hypertension control at follow-up visits was higher among HIV-infected patients than uninfected patients to have controlled blood pressure at follow-up visits (48% vs 46%; aOR 1.28; 95% CI 0.95-1.71). CONCLUSIONS: Improved HTN control was achieved in an integrated HIV and chronic care model. Similar to HIV care, visit frequency determined by drug supply chain rather than clinical indication is associated with worse HTN control. TRIAL REGISTRATION: The SEARCH Trial was prospectively registered with ClinicalTrials.gov : NCT01864603.

A Patient-Centered Multicomponent Strategy for Accelerated Linkage to Care Following Community-Wide HIV Testing in Rural Uganda and Kenya.

INTRODUCTION: As countries move toward universal HIV treatment, many individuals fail to link to care after diagnosis of HIV. Efficient and effective linkage strategies are needed. METHODS: We implemented a patient-centered, multicomponent linkage strategy in the SEARCH "test-and-treat" trial (NCT 01864603) in Kenya and Uganda. After population-based, community-wide HIV testing, eligible participants were (1) introduced to clinic staff after testing, (2) provided a telephone "hot-line" for enquiries, (3) provided an appointment reminder phone call, (4) given transport reimbursement on linkage, and (5) tracked if linkage appointment was missed. We estimated the proportion linked to care within 1 year and evaluated factors associated with linkage at 7, 30, and 365 days after diagnosis. RESULTS: Among 71,308 adults tested, 6811 (9.6%) were HIV-infected; of these, 4760 (69.9%) were already in HIV care, and 30.1% were not. Among 2051 not in care, 58% were female, median age was 32 (interquartile range 26-40) years, and median CD4 count was 493 (interquartile range 331-683) cells/µL. Half (49.7%) linked within 1 week, and 73.4% linked within 1 year. Individuals who were younger [15-34 vs. >35 years, adjusted Risk Ratio (aRR) 0.83, 95% confidence interval (CI): 0.74 to 0.94], tested at home vs. community campaign (aRR = 0.87, 95% CI: 0.81 to 0.94), had a high HIV-risk vs. low-risk occupation (aRR = 0.81, 95% CI: 0.75 to 0.88), and were wealthier (aRR 0.90, 95% CI: 0.83 to 0.97) were less likely to link. Linkage did not differ by marital status, stable residence, level of education, or having a phone contact. CONCLUSIONS: Using a multicomponent linkage strategy, high proportions of people living with HIV but not in care linked rapidly after HIV testing.

Factors predictive of successful retention in care among HIV-infected men in a universal test-and-treat setting in Uganda and Kenya: A mixed methods analysis.

BACKGROUND: Previous research indicates clinical outcomes among HIV-infected men in sub-Saharan Africa are sub-optimal. The SEARCH test and treat trial (NCT01864603) intervention included antiretroviral care delivery designed to address known barriers to HIV-care among men by decreasing clinic visit frequency and providing flexible, patient-centered care with retention support. We sought to understand facilitators and barriers to retention in care in this universal treatment setting through quantitative and qualitative data analysis. METHODS: We used a convergent mixed methods study design to evaluate retention in HIV care among adults (age > = 15) during the first year of the SEARCH (NCT01864603) test and treat trial. Cox proportional hazards regression was used to evaluate predictors of retention in care. Longitudinal qualitative data from n = 190 in-depth interviews with HIV-positive individuals and health care providers were analyzed to identify facilitators and barriers to HIV care engagement. RESULTS: There were 1,863 men and 3,820 women who linked to care following baseline testing. Retention in care was 89.7% (95% CI 87.0-91.8%) among men and 89.0% (86.8-90.9%) among women at one year. In both men and women older age was associated with higher rates of retention in care at one year. Additionally, among men higher CD4+ at ART initiation and decreased time between testing and ART initiation was associated with higher rates of retention. Maintaining physical health, a patient-centered treatment environment, supportive partnerships, few negative consequences to disclosure, and the ability to seek care in facilities outside of their community of residence were found to promote retention in care. CONCLUSIONS: Features of the ART delivery system in the SEARCH intervention and social and structural advantages emerged as facilitators to retention in HIV care among men. Messaging around the health benefits of early ART start, decreasing logistical barriers to HIV care, support of flexible treatment environments, and accelerated linkage to care, are important to men's success in ART treatment programs. Men already benefit from increased social support following disclosure of their HIV-status. Future efforts to shift gender norms towards greater equity are a potential strategy to support high levels of engagement in care for both men and women.

Costs of streamlined HIV care delivery in rural Ugandan and Kenyan clinics in the SEARCH Studys.

OBJECTIVES/DESIGN: As antiretroviral therapy (ART) rapidly expands in sub-Saharan Africa using new efficient care models, data on costs of these approaches are lacking. We examined costs of a streamlined HIV care delivery model within a large HIV test-and-treat study in Uganda and Kenya. METHODS: We calculated observed per-person-per-year (ppy) costs of streamlined care in 17 health facilities in SEARCH Study intervention communities (NCT: 01864603) via micro-costing techniques, time-and-motion studies, staff interviews, and administrative records. Cost categories included salaries, ART, viral load testing, recurring goods/services, and fixed capital/facility costs. We then modeled costs under three increasingly efficient scale-up scenarios: lowest-cost ART, centralized viral load testing, and governmental healthcare worker salaries. We assessed the relationship between community-specific ART delivery costs, retention in care, and viral suppression. RESULTS: Estimated streamlined HIV care delivery costs were $291/ppy. ART ($117/ppy for TDF/3TC/EFV [40%]) and viral load testing ($110/ppy for 2 tests/year [39%]) dominated costs versus salaries ($51/ppy), recurring costs ($5/ppy), and fixed costs ($7/ppy). Optimized ART scale-up with lowest-cost ART ($100/ppy), annual viral load testing ($24/ppy), and governmental healthcare salaries ($27/ppy), lowered streamlined care cost to $163/ppy. We found clinic-to-clinic heterogeneity in retention and viral suppression levels versus streamlined care delivery costs, but no correlation between cost and either retention or viral suppression. CONCLUSIONS: In the SEARCH Study, streamlined HIV care delivery costs were similar to or lower than prior estimates despite including viral load testing; further optimizations could substantially reduce costs further. These data can inform global strategies for financing ART expansion to achieve UNAIDS 90-90-90 targets.

High levels of retention in care with streamlined care and universal test and treat in East Africa.

OBJECTIVE: We sought to measure retention in care and identify predictors of nonretention among patients receiving antiretroviral therapy (ART) with streamlined delivery during the first year of the ongoing Sustainable East Africa Research on Community Health (SEARCH) 'test-and-treat' trial (NCT 01864603) in rural Uganda and Kenya. DESIGN: Prospective cohort of patients in the intervention arm of the SEARCH study. METHODS: We measured retention in care at 12 months among HIV-infected adults who linked to care and were offered ART regardless of CD4 cell count, following community-wide HIV-testing. Kaplan-Meier estimates and Cox proportional hazards modeling were used to calculate the probability of retention at 1 year and identify predictors of nonretention. RESULTS: Among 5683 adults (age ≥15) who linked to care, 95.5% [95% confidence interval (CI): 92.9-98.1%] were retained in care at 12 months. The overall probability of retention at 1 year was 89.3% (95% CI: 87.6-90.7%) among patients newly linking to care and 96.4% (95% CI: 95.8-97.0%) among patients previously in care. Younger age and pre-ART CD4 cell count below country treatment initiation guidelines were predictors of nonretention among all patients. Among those newly linking, taking more than 30 days to link to care after HIV diagnosis was additionally associated with nonretention at 1 year. HIV viral load suppression at 12 months was observed in 4227 of 4736 (89%) of patients retained with valid viral load results. CONCLUSION: High retention in care and viral suppression after 1 year were achieved in a streamlined HIV care delivery system in the context of a universal test-and-treat intervention.

Cost-effectiveness of provider-based HIV partner notification in urban Malawi.

Provider-initiated partner notification for HIV effectively identifies new cases of HIV in sub-Saharan Africa, but is not widely implemented. Our objective was to determine whether provider-based HIV partner notification strategies are cost-effective for preventing HIV transmission compared with passive referral. We conducted a cost-effectiveness analysis using a decision-analytic model from the health system perspective during a 1-year period. Costs and outcomes of all strategies were estimated with a decision-tree model. The study setting was an urban sexually transmitted infection clinic in Lilongwe, Malawi, using a hypothetical cohort of 5000 sex partners of 3500 HIV-positive index cases. We evaluated three partner notification strategies: provider notification (provider attempts to notify indexes' locatable partners), contract notification (index given 1 week to notify partners then provider attempts notification) and passive referral (index is encouraged to notify partners, standard of care). Our main outcomes included cost (US dollars) per transmission averted, cost per new case identified and cost per partner tested. Based on estimated transmissions in a 5000-person cohort, provider and contract notification averted 27.9 and 27.5 new infections, respectively, compared with passive referral. The incremental cost-effectiveness ratio (ICER) was $3560 per HIV transmission averted for contract notification compared with passive referral. Provider notification was more expensive and slightly more effective than contract notification, yielding an ICER of $51 421 per transmission averted. ICERs were sensitive to the proportion of partners not contacted, but likely HIV positive and the probability of transmission if not on antiretroviral therapy. The costs per new case identified were $36 (provider), $18 (contract) and $8 (passive). The costs per partner tested were $19 (provider), $9 (contract) and $4 (passive). We conclude that, in this population, provider-based notification strategies are potentially cost-effective for identifying new cases of HIV. These strategies offer a simple, effective and easily implementable opportunity to control HIV transmission.

The feasibility of an intensive case management program for injection drug users on antiretroviral therapy in St. Petersburg, Russia.

BACKGROUND: The majority of HIV-infected individuals requiring antiretroviral therapy (ART) in Russia are Injection Drug Users (IDU). Substitution therapy used as part of a comprehensive harm reduction program is unavailable in Russia. Past data shows that only 16% of IDU receiving substance abuse treatment completed the course without relapse, and only 40% of IDU on ART remained on treatment at 6 months. Our goal was to determine if it was feasible to improve these historic outcomes by adding intensive case management (ICM) to the substance abuse and ART treatment programs for IDU. METHODS: IDU starting ART and able to involve a "supporter" who would assist in their treatment plan were enrolled. ICM included opiate detoxification, bi-monthly contact and counseling with the case, weekly group sessions, monthly contact with the "supporter" and home visits as needed. Full follow- up (FFU) was 8 months. Stata v10 (College Station, TX) was used for all analysis. Descriptive statistics were calculated for all baseline demographic variables, baseline and follow-up CD4 count, and viral load. Median baseline and follow-up CD4 counts and RNA levels were compared using the Kruskal-Wallis test. The proportion of participants with RNA < 1000 copies mL at baseline and follow-up was compared using Fisher's Exact test. McNemar's test for paired proportions was used to compare the change in proportion of participants with RNA < 1000 copies mL from baseline to follow-up. RESULTS: Between November 2007 and December 2008, 60 IDU were enrolled. 34 (56.7%) were male. 54/60 (90.0%) remained in FFU. Overall, 31/60 (52%) were active IDU at enrollment and 27 (45%) were active at their last follow-up visit. 40/60 (66.7%) attended all of their ART clinic visits, 13/60 (21.7%) missed one or more visit but remained on ART, and 7/60 (11.7%) stopped ART before the end of FFU. Overall, 39/53 (74%) had a final 6-8 month HIV RNA viral load (VL) < 1000 copies/mL. CONCLUSIONS: Despite no substitution therapy to assist IDU in substance abuse and ART treatment programs, ICM was feasible, and the retention and adherence of IDU on ART in St. Petersburg could be greatly enhanced by adding ICM to the existing treatment programs.

Predicting partner HIV testing and counseling following a partner notification intervention.

Provider-assisted methods of partner notification increase testing and counseling among sexual partners of patients diagnosed with HIV, however they are resource-intensive. The sexual partners of individuals enrolled in a clinical trial comparing different methods of HIV partner notification were analyzed to identify who was unlikely to seek testing on their own. Unconditional logistic regression was used to identify partnership characteristics, which were assigned a score based on their coefficient in the final model, and a risk score was calculated for each participant. The risk score included male partner sex, relationship duration 6-24 months, and index education > primary. A risk score of ≥ 2 had a sensitivity of 68% and specificity of 78% in identifying partners unlikely to seek testing on their own. A risk score to target partner notification can reduce the resources required to locate all partners in the community while increasing the testing yield compared to patient-referral.

Detection of acute HIV infection: a field evaluation of the determine® HIV-1/2 Ag/Ab combo test.

BACKGROUND: Most human immunodeficiency virus (HIV) point-of-care tests detect antibodies (Ab) but not p24 antigen (Ag) or RNA. In the absence of antibodies, p24 antigen and RNA typically indicate acute HIV infection. We conducted a field evaluation of the Determine® HIV-1/2 Ag/Ab Combo rapid test (Combo RT). METHODS: The antigen portion of the Combo RT (for acute HIV infection) was compared with a Roche Monitor HIV RNA polymerase chain reaction assay. The antibody portion of Combo RT (for established HIV infection) was compared with rapid test algorithms. Participants were enrolled at a sexually transmitted infection clinic and HIV testing and counseling center in Lilongwe, Malawi. Rapid testing was conducted with parallel testing in the clinic and serial testing in the center. The Combo RT was performed in clinic participants with negative or discordant antibody results and in all center participants. RESULTS: Of the participants 838 were HIV negative, 163 had established HIV infection, and 8 had acute HIV infection. For detecting acute HIV infection, the antigen portion had a sensitivity of 0.000 and a specificity of 0.983. For detecting established HIV infection, the antibody portion had a sensitivity of 0.994 and a specificity of 0.992. CONCLUSIONS: Combo RT displayed excellent performance for detecting established HIV infection and poor performance for detecting acute HIV infection. In this setting, Combo RT is no more useful than current algorithms.

HIV partner notification is effective and feasible in sub-Saharan Africa: opportunities for HIV treatment and prevention.

BACKGROUND: Sexual partners of persons with newly diagnosed HIV infection require HIV counseling, testing and, if necessary, evaluation for therapy. However, many African countries do not have a standardized protocol for partner notification, and the effectiveness of partner notification has not been evaluated in developing countries . METHODS: Individuals with newly diagnosed HIV infection presenting to sexually transmitted infection clinics in Lilongwe, Malawi, were randomized to 1 of 3 methods of partner notification: passive referral, contract referral, or provider referral. The passive referral group was responsible for notifying their partners themselves. The contract referral group was given seven days to notify their partners, after which a health care provider contacted partners who had not reported for counseling and testing. In the provider referral group, a health care provider notified partners directly. RESULTS: Two hundred forty-five index patients named 302 sexual partners and provided locator information for 252. Among locatable partners, 107 returned for HIV counseling and testing; 20 of 82 [24%; 95% confidence interval (CI): 15% to 34%] partners returned in the passive referral arm, 45 of 88 (51%; 95% CI: 41% to 62%) in the contract referral arm, and 42 of 82 (51%; 95% CI: 40% to 62%) in the provider referral arm (P < 0.001). Among returning partners (n = 107), 67 (64%) of were HIV infected with 54 (81%) newly diagnosed. DISCUSSION: This study provides the first evidence of the effectiveness of partner notification in sub-Saharan Africa. Active partner notification was feasible, acceptable, and effective among sexually transmitted infections clinic patients. Partner notification will increase early referral to care and facilitate risk reduction among high-risk uninfected partners.

Accelerating worldwide syphilis screening through rapid testing: a systematic review.

Syphilis is a persistent public health issue in many low-income countries that have limited capacity for testing, which traditionally relies on a sensitive non-treponemal test and then a specific treponemal test. However, the development of a new rapid treponemal test provides an opportunity to scale up syphilis screening in many settings where traditional tests are unavailable. This systematic review of immunochromatographic strip (ICS) syphilis tests describes the sensitivity and specificity in two important clinical settings: sexually transmitted infection (STI) clinics and antenatal clinics. Clinical data from more than 22 000 whole blood, plasma, or fingerstick ICS tests obtained at STI or antenatal clinics were retrieved from 15 studies. ICS syphilis tests have a high sensitivity (median 0.86, interquartile range 0.75-0.94) and a higher specificity (0.99, 0.98-0.99), both comparable with non-treponemal screening test characteristics. Further research evaluating ICS syphilis tests among primary syphilis cases and among patients infected with HIV will be essential for the effective roll-out of syphilis screening programmes.