Using viral sequence diversity to estimate time of HIV infection in infants.

Age at HIV acquisition may influence viral pathogenesis in infants, and yet infection timing (i.e. date of infection) is not always known. Adult studies have estimated infection timing using rates of HIV RNA diversification, however, it is unknown whether adult-trained models can provide accurate predictions when used for infants due to possible differences in viral dynamics. While rates of viral diversification have been well defined for adults, there are limited data characterizing these dynamics for infants. Here, we performed Illumina sequencing of gag and pol using longitudinal plasma samples from 22 Kenyan infants with well-characterized infection timing. We used these data to characterize viral diversity changes over time by designing an infant-trained Bayesian hierarchical regression model that predicts time since infection using viral diversity. We show that diversity accumulates with time for most infants (median rate within pol = 0.00079 diversity/month), and diversity accumulates much faster than in adults (compare previously-reported adult rate within pol = 0.00024 diversity/month [1]). We find that the infant rate of viral diversification varies by individual, gene region, and relative timing of infection, but not by set-point viral load or rate of CD4+ T cell decline. We compare the predictive performance of this infant-trained Bayesian hierarchical regression model with simple linear regression models trained using the same infant data, as well as existing adult-trained models [1]. Using an independent dataset from an additional 15 infants with frequent HIV testing to define infection timing, we demonstrate that infant-trained models more accurately estimate time since infection than existing adult-trained models. This work will be useful for timing HIV acquisition for infants with unknown infection timing and for refining our understanding of how viral diversity accumulates in infants, both of which may have broad implications for the future development of infant-specific therapeutic and preventive interventions.

Partner Characteristics and HIV Outcomes among Partners Reached by Phone vs. In-person for Assisted Partner Services in Western Kenya.

BACKGROUND: Assisted partner services (APS) is an effective strategy for testing people with undiagnosed HIV but there is limited information on the relative reach and effectiveness of phone versus in-person contact. METHODS: We analyzed data from 31 facilities in Western Kenya providing APS to female index clients newly HIV-diagnosed, their male partners, and female partners of men newly HIV-diagnosed. APS providers attempted contacting partners using phone first and, if unsuccessful, in-person in the community. Using log-linear mixed models, we estimated relative risks (RR) between phone being the final contact method and partner characteristics and HIV outcomes. RESULTS: From May 2018-March 2020, 2534 female index clients named 7614 male partners, of whom 772 (10.1%) tested positive and named an additional 4956 non-index female partners. Of 11,912 (94.7%) partners reached, 5179 (43.5%) were via phone and 6733 (56.5%) in-person. Of 8076 testing-eligible partners, 99.7% tested and 11.2% first-time tested. Of those tested, 13.1% were newly-diagnosed, of whom 87.0% linked to care. Newly-diagnosed partners were less likely to have been reached by phone vs. in-person (9.8% vs. 15.9%; adjusted RR:0.61, 95%CI:0.53-0.70). Being reached by phone was not significantly associated with testing, first-time testing, or linkage to care. CONCLUSIONS: In an APS program that reached 94% of elicited partners, fewer than half were successfully contacted by phone. A combined phone and in-person approach is likely essential for equitable, effective APS.

HIV testing services and HIV self-testing programming within emergency care in Kenya: a qualitative study of healthcare personnel to inform enhanced service delivery approaches.

In Kenya, persons insufficiently engaged in HIV Testing Services (HTS) are often treated in emergency departments (ED). There are limited data from healthcare workers on ED-HTS. A qualitative study was completed to understand challenges and facilitators for ED-HTS and HIV self-testing (HIVST). Data were collected via six focus groups of healthcare workers. Data were inductively analyzed and mapped to the Capability-Opportunity-Motivation Behavioral Model. Focus groups were completed with 49 healthcare workers: 18 nurses, 15 HIV counselors, 10 physicians and 6 administrators. HTS challenges included staff burdens, resources access, deficiencies in systems integration and illness severity. HTS facilitators included education of healthcare workers and patients, services coordination, and specific follow-up processes. HIVST challenges included accuracy concerns, follow-up barriers and psychosocial risks. HIVST facilitators were patient autonomy and confidentiality, resource utilization and ability to reach higher-risk persons. Mapping to the Capability-Opportunity-Motivation Behavioral Model interventions within the domains of knowledge, decision processes, environmental aspects, social influences and professional identities could support enhanced ED-HTS with integrated HIVST delivery. This study provided insights into challenges and facilitators on ED-HTS and identifies pragmatic approaches to improve healthcare workers' behaviors and abilities to provide services to persons already in contact with healthcare.

Characteristics associated with HIV and hepatitis C seroprevalence among sexual and injecting partners of HIV positive persons who inject drugs in Nairobi and coastal Kenya.

BACKGROUND: Persons who inject drugs (PWID) have higher HIV and hepatitis C virus (HCV) seroprevalence than the general population in many parts of sub-Saharan Africa (SSA). The seroprevalences of HIV and HCV are also higher in coastal Kenya than in Nairobi. Understanding drivers of regional HIV and HCV variation among PWID in Kenya may inform population-specific prevention interventions. METHODS: Using a cross-sectional study, we defined HIV and HCV seroprevalence among persons identified as sexual or injecting partners of HIV positive PWID in two regions of Kenya and used logistic regression to identify demographic and behavioral characteristics associated with higher seroprevalence. RESULTS: Among 2386 partners, 469 (19.7%) tested HIV positive and 297(12.4%) tested HCV antibody positive. Partners on the Coast were more likely to live with HIV (seroprevalences: Coast = 23.8%, Nairobi = 17.1%; p < 0.001) and be HCV antibody positive (seroprevalences: Coast = 17.0%, Nairobi = 8.6%; p < 0.001). After adjusting for sex, age, and years injecting and accounting for clustering by site, the higher prevalence of both diseases in the Coast remained significant for HIV (OR 1.68, 95% CI 1.13-2.51) but not for HCV (OR 1.72, 95% CI 0.84-3.74). Compared to those recruited in Nairobi, partners on the Coast were older (Coast = 35 years, Nairobi = 31 years; p < 0.001), more likely to be male (Coast = 77.6%, Nairobi = 61.7%; p < 0.001), to have paid (Coast = 59.2%, Nairobi = 32.8%; p < 0.001) or received (Coast = 44.2%, Nairobi 35.4%; p < 0.001) money for sex, or to have had sex with someone they knew to be HIV positive (Coast 22.0%, Nairobi 10.8%; p < 0.001). Partners who had injected for five or more years had 1.48 times greater odds (95% CI 1.20-1.82) of living with HIV compared to partners who injected less than 5 years and more than twice the odds of HCV (95% CI 1.84-4.11). CONCLUSION: HIV and HCV seroprevalence among sexual and injecting partners of PWID was, respectively, 5 times and > 12 times greater than is reported among the general population in Kenya (4% and < 1%, respectively). Providing resources and education will be crucial to reduce exposure and to maintain the lower needle and equipment sharing that we observed compared to other studies.

Cost of integrating assisted partner services in HIV testing services in Kisumu and Homa Bay counties, Kenya: a microcosting study.

BACKGROUND: HIV assisted partner services (aPS), or provider notification and testing for sexual and injecting partners of people diagnosed with HIV, is shown to be safe, effective, and cost-effective and was scaled up within the national HIV testing services (HTS) program in Kenya in 2016. We estimated the costs of integrating aPS into routine HTS within an ongoing aPS scale-up project in western Kenya. METHODS: We conducted microcosting using the payer perspective in 14 facilities offering aPS. Although aPS was offered to both males and females testing HIV-positive (index clients), we only collected data on female index clients and their male sex partners (MSP). We used activity-based costing to identify key aPS activities, inputs, resources, and estimated financial and economic costs of goods and services. We analyzed costs by start-up (August 2018), and recurrent costs one-year after aPS implementation (Kisumu: August 2019; Homa Bay: January 2020) and conducted time-and-motion observations of aPS activities. We estimated the incremental costs of aPS, average cost per MSP traced, tested, testing HIV-positive, and on antiretroviral therapy, cost shares, and costs disaggregated by facility. RESULTS: Overall, the number of MSPs traced, tested, testing HIV-positive, and on antiretroviral therapy was 1027, 869, 370, and 272 respectively. Average unit costs per MSP traced, tested, testing HIV-positive, and on antiretroviral therapy were $34.54, $42.50, $108.71 and $152.28, respectively, which varied by county and facility client volume. The weighted average incremental cost of integrating aPS was $7,485.97 per facility per year, with recurrent costs accounting for approximately 90% of costs. The largest cost drivers were personnel (49%) and transport (13%). Providers spent approximately 25% of the HTS visit obtaining MSP contact information (HIV-negative clients: 13 out of 54 min; HIV-positive clients: 20 out of 96 min), while the median time spent per MSP traced on phone and in-person was 6 min and 2.5 hours, respectively. CONCLUSION: Average facility costs will increase when integrating aPS to HTS with incremental costs largely driven by personnel and transport. Strategies to efficiently utilize healthcare personnel will be critical for effective, affordable, and sustainable aPS.

"It is a process" - a qualitative evaluation of provider acceptability of HIV assisted partner services in western Kenya: experiences, challenges, and facilitators.

BACKGROUND: Assisted partner service (APS) is effective for increasing HIV testing services (HTS) uptake among sexual partners of people diagnosed with HIV with rare social harm. The acceptability of APS to HTS providers is important for the quality and effectiveness of APS delivery. Within a larger ongoing implementation science study of APS in western Kenya, we qualitatively evaluated the provider acceptability of APS. METHODS: From May-June 2020, we conducted virtual, semi-structured in-depth interviews with 14 HTS providers recruited from 8 of 31 study health facilities in Homa Bay and Kisumu counties. Participants were selected using criteria-based purposive sampling to maximize variation on patient volume (assessed by the number of index clients tested for HIV) and APS performance (assessed by sexual partners elicitation and enrollment). Interviews inquired providers' experiences providing APS including challenges and facilitators and the impact of contextual factors. Data were analyzed using an inductive approach. RESULTS: Overall, HTS providers found APS acceptable. It was consistently reported that doing APS was a continuous process rather than a one-day job, which required building rapport and persistent efforts. Benefits of APS including efficiency in HIV case finding, expanded testing coverage in men, and increased HIV status awareness and linkage to care motivated the providers. Provider referral was perceived advantageous in terms of independent contact with partners on behalf of index clients and efficiency in partner tracing. Challenges of providing APS included protecting clients' confidentiality, difficulty obtaining partners' accurate contact information, logistic barriers of tracing, and clients' refusal due to fear of being judged for multiple sexual partners, fear of breach of confidentiality, and HIV stigma. Building rapport with clients, communicating with patience and nonjudgmental attitude and assuring confidentiality were examples of facilitators. Working in rural areas and bigger facilities, training, supportive supervision, and community awareness of APS promoted APS delivery while low salaries, lack of equipment, and high workload undermined it. CONCLUSIONS: HTS providers found APS acceptable. Delivering APS as a process was the key to success. Future scale-up of APS could consider encouraging provider referral instead of the other APS methods to improve efficiency and reduce potential harm to clients.

A High-throughput Bead-based Affinity Assay Enables Analysis of Genital Protein Signatures in Women At Risk of HIV Infection.

Women at high risk of HIV infection, including sex workers and those with active genital inflammation, have molecular signatures of immune activation and epithelial barrier remodeling in samples of their genital mucosa. These alterations in the local immunological milieu are likely to impact HIV susceptibility. We here analyze host genital protein signatures in HIV uninfected women, with high frequency of condom use, living in HIV-serodiscordant relationships. Cervicovaginal secretions from women living in HIV-serodiscordant relationships (n = 62) were collected at three time points over 12 months. Women living in HIV-negative seroconcordant relationships (controls, n = 25) were sampled at one time point. All study subjects were examined for demographic parameters associated with susceptibility to HIV infection. The cervicovaginal samples were analyzed using a high-throughput bead-based affinity assay. Proteins involved in epithelial barrier function and inflammation were increased in HIV-serodiscordant women. By combining several methods of analysis, a total of five proteins (CAPG, KLK10, SPRR3, elafin/PI3, CSTB) were consistently associated with this study group. Proteins analyzed using the affinity set-up were further validated by label-free tandem mass spectrometry in a partially overlapping cohort with concordant results. Women living in HIV-serodiscordant relationships thus had elevated levels of proteins involved in epithelial barrier function and inflammation despite low prevalence of sexually transmitted infections and a high frequency of safe sex practices. The identified proteins are important markers to follow during assessment of mucosal HIV susceptibility factors and a high-throughput bead-based affinity set-up could be a suitable method for such evaluation.

Women's Autonomy in Infant Feeding Decision-Making: A Qualitative Study in Nairobi, Kenya.

BACKGROUND: Exclusive breastfeeding (EBF) is the optimal way to feed young infants. Guidelines recommend that women living with HIV on antiretroviral therapy should EBF for 6 months and continue breastfeeding for up to 24 months or longer. Parents may face social or logistical barriers creating challenges to EBF. OBJECTIVES: To explore barriers, facilitators and community norms influencing EBF practices in Kenya. METHODS: This qualitative research was nested within a longitudinal study of intensive maternal counseling to increase EBF among HIV-positive mothers. HIV-negative and HIV-positive mothers were recruited from four public clinics in Nairobi. Women participated in focus group discussions (FGDs) that explored beliefs about and experiences with infant feeding. Conventional content analysis was used to describe and compare barriers and facilitators influencing HIV-positive and HIV-negative women's EBF experiences. RESULTS: We conducted 17 FGDs with 80 HIV-positive and 53 HIV-negative women between 2009 and 2012. Overall, women agreed that breastmilk is good for infants. However, early mixed feeding was a common cultural practice. HIV-positive women perceived that infant feeding methods and durations were their decision. In contrast, HIV-negative women reported less autonomy and more mixed feeding, citing peer pressure and lack of HIV transmission concerns. Autonomy in decision-making was facilitated by receiving EBF counseling and family support, especially from male partners. Low milk production was a barrier to EBF, regardless of HIV status, and perceived to represent poor maternal nutrition. CONCLUSIONS: Despite challenges, counseling empowered women living with HIV to advocate for EBF with spouses and family.

Human papillomavirus and abnormal cervical lesions among HIV-infected women in HIV-discordant couples from Kenya.

OBJECTIVE: HIV infection increases the risk of high-grade cervical neoplasia and invasive cervical carcinoma. The study addresses the limited data describing human papillomavirus (HPV) infection and cervical neoplasia among HIV-infected women in HIV-discordant relationships in sub-Saharan Africa, which is needed to inform screening strategies. METHODS: A cross-sectional study of HIV-infected women with HIV-uninfected partners was conducted to determine the distribution of type-specific HPV infection and cervical cytology. This study was nested in a prospective cohort recruited between September 2007 and December 2009 in Nairobi, Kenya. Cervical cells for HPV DNA testing and conventional cervical cytology were collected. HPV types were detected and genotyped by Roche Linear Array PCR assay. RESULTS: Among 283 women, the overall HPV prevalence was 62%, and 132 (47%) had ≥1 high-risk (HR)-HPV genotype. Of 268 women with cervical cytology results, 18 (7%) had high-grade cervical lesions or more severe by cytology, of whom 16 (89%) were HR-HPV-positive compared with 82 (41%) of 199 women with normal cytology (p<0.001). The most common HR-HPV types in women with a high-grade lesion or more severe by cytology were HPV-52 (44%), HPV-31 (22%), HPV-35 (22%), HPV-51 (22%) and HPV-58 (22%). HR-HPV genotypes HPV-16 or HPV-18 were found in 17% of women with high-grade lesions or more severe. HR-HPV screening applied in this population would detect 89% of those with a high-grade lesion or more severe, while 44% of women with normal or low-grade cytology would screen positive. CONCLUSION: HR-HPV prevalence was high in this population of HIV-infected women with an uninfected partner. Choice of screening for all HR genotypes versus a subset of HR genotypes in these HIV-infected women will strongly affect the performance of an HPV screening strategy relative to cytological screening. Regional and subpopulation differences in HR-HPV genotype distributions could affect screening test performance.

Birth size and early pneumonia predict linear growth among HIV-exposed uninfected infants.

Stunting remains a global health priority, particularly in sub-Saharan Africa. Identifying determinants of linear growth in HIV-exposed uninfected (HEU) infants can inform interventions to prevent stunting in this vulnerable population. HIV-infected mothers and their uninfected infants were followed monthly from pregnancy to 12-month post-partum in Nairobi, Kenya. Mixed-effects models estimated the change in length-for-age z-score (LAZ) from birth to 12 months by environmental, maternal, and infant characteristics. Multivariable models included factors univariately associated with LAZ. Among 372 HEU infants, mean LAZ decreased from -0.54 (95% confidence interval [CI] [-0.67, -0.41]) to -1.09 (95% CI [-1.23, -0.96]) between 0 and 12 months. Declines in LAZ were associated with crowding (≥2 persons per room; adjusted difference [AD] in 0-12 month change: -0.46; 95% CI [-0.87, -0.05]), use of a pit latrine versus a flush toilet (AD: -0.29; 95% CI [-0.57, -0.02]), and early infant pneumonia (AD: -1.14; 95% CI [-1.99, -0.29]). Infants with low birthweight (<2,500 g; AD: 1.08; 95% CI [0.40, 1.76]) and birth stunting (AD: 1.11; 95% CI [0.45, 1.78]) experienced improved linear growth. By 12 months of age, 46 infants were stunted, of whom 11 (24%) were stunted at birth. Of the 34 infants stunted at birth with an available 12-month LAZ, 68% were not stunted at 12 months. Some low birthweight and birth-stunted HEU infants had significant linear growth recovery. Early infant pneumonia and household environment predicted poor linear growth and may identify a subgroup of HEU infants for whom to provide growth-promoting interventions.

Genital Injury Signatures and Microbiome Alterations Associated With Depot Medroxyprogesterone Acetate Usage and Intravaginal Drying Practices.

Background: Increasing evidence suggests depot medroxyprogesterone acetate (DMPA) and intravaginal practices may be associated with human immunodeficiency virus (HIV-1) infection risk; however, the mechanisms are not fully understood. This study evaluated the effect of DMPA and intravaginal practices on the genital proteome and microbiome to gain mechanistic insights. Methods: Cervicovaginal secretions from 86 Kenyan women, including self-reported DMPA users (n = 23), nonhormonal contraceptive users (n = 63), and women who practice vaginal drying (n = 46), were analyzed using tandem-mass spectrometry. Results: We identified 473 human and 486 bacterial proteins from 18 different genera. Depot medroxyprogesterone acetate use associated with increased hemoglobin and immune activation (HBD, HBB, IL36G), and decreased epithelial repair proteins (TFF3, F11R). Vaginal drying associated with increased hemoglobin and decreased phagocytosis factors (AZU1, MYH9, PLAUR). Injury signatures were exacerbated in DMPA users who also practiced vaginal drying. More diverse (H index: 0.71 vs 0.45; P = .009) bacterial communities containing Gardnerella vaginalis associated with vaginal drying, whereas DMPA showed no significant association with community composition or diversity. Conclusions: These findings provide new insights into the impact of DMPA and vaginal drying on mucosal barriers. Future investigations are needed to confirm their relationship with HIV risk in women.

Low HDL-cholesterol among HIV-1 infected and HIV-1 uninfected individuals in Nairobi, Kenya.

BACKGROUND: Antiretroviral treatment (ART) is associated with dyslipidemia yet little is known about the burden of dyslipidemia in the absence of ART in sub-Saharan Africa. We compared the prevalence and risk factors for dyslipidemia among HIV-infected ART-naïve adults and their uninfected partners in Nairobi, Kenya. METHODS: Non-fasting total cholesterol (TC) and high density lipoprotein cholesterol (HDL) levels were measured by standard lipid spectrophotometry on thawed plasma samples obtained from HIV-infected participants and their uninfected partners. Dyslipidemia, defined by high TC (>200 mg/dl) or low HDL (<40 mg/dl) was compared between HIV-infected and uninfected men and women. RESULTS: Among 196 participants, median age was 32 years [IQR: 23-41]. Median CD4 count among the HIV-infected was 393 cells/ µl (IQR: 57-729) and 90% had a viral load >1000 copies/ml. Mean TC and HDL were comparable for HIV-infected and uninfected participants. Prevalence of dyslipidemia was 83.8% vs 78.4% (p = 0.27). Among the HIV-infected, those with a viral load >1000 copies/ml were 1.5-fold more likely to have dyslipidemia compared to those with ≤1000 copies/ml (adjusted prevalence ratio [aPR] 1.5, 95% CI: 1.22-30.99, p = 0.02). BMI, age, gender, blood pressure and smoking were not significantly associated with dyslipidemia. CONCLUSIONS: Among ART-naïve HIV-infected adults, high viral load and low CD4 cell count were independent predictors of dyslipidemia, underscoring the importance of early initiation of ART for viral suppression.

High rates of relationship dissolution among heterosexual HIV-serodiscordant couples in Kenya.

HIV-1 serodiscordant couples may experience increased risks of relationship dissolution; however, longitudinal stability of these relationships is poorly understood. We determined rates and correlates of separation among 469 serodiscordant couples in Nairobi and found that 113 (24 %) separated during 2 years of follow-up. Couples with a female HIV-1 infected partner (F+M-) and no income were more likely to separate than M+F- couples without income (HR = 5.0; 95 % CI 1.1-25.0), and F+M- and M+F- couples with income (HR = 2.4; 95 % CI 1.3-4.5 and HR = 2.3; 95 % CI 1.2-4.8, respectively). High separation rates may be important for couple support services and for conducting discordant couple studies.

Correlates and outcomes of preterm birth, low birth weight, and small for gestational age in HIV-exposed uninfected infants.

BACKGROUND: Preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA) contribute to neonatal mortality. Maternal HIV-1 infection has been associated with an increased risk of PTB, but mechanisms underlying this association are undefined. We describe correlates and outcomes of PTB, LBW, and SGA in HIV-exposed uninfected infants. METHODS: This was a retrospective analysis of cohort study. Between 1999-2002, pregnant, HIV-infected women were enrolled into an HIV-1 transmission study. Logistic regression was used to identify correlates of PTB, LBW and SGA in HIV-negative, spontaneous singleton deliveries. Associations between birth outcomes and mortality were measured using survival analyses. RESULTS: In multivariable models, maternal plasma (OR = 2.1, 95% CI = 1.1-3.8) and cervical HIV-1 RNA levels (OR = 1.6, 95% CI = 1.1-2.4), and CD4 < 15% (OR = 2.4, 95% CI = 1.0-5.6) were associated with increased odds of PTB. Abnormal vaginal discharge and cervical polymorphonuclear leukocytes were also associated with PTB. Cervical HIV-1 RNA level (OR = 2.4, 95% CI = 1.5-6.7) was associated with an increased odds of LBW, while increasing parity (OR = 0.46, 95% CI = 0.24-0.88) was associated with reduced odds. Higher maternal body mass index (OR = 0.75, 95% CI = 0.61-0.92) was associated with a reduced odds of SGA, while bacterial vaginosis was associated with >3-fold increased odds (OR = 3.2, 95% CI = 1.4-7.4). PTB, LBW, and SGA were each associated with a >6-fold increased risk of neonatal death, and a >2-fold increased rate of infant mortality within the first year. CONCLUSIONS: Maternal plasma and cervical HIV-1 RNA load, and genital infections may be important risk factors for PTB in HIV-exposed uninfected infants. PTB, LBW, and SGA are associated with increased neonatal and infant mortality in HIV-exposed uninfected infants.

Incident HSV-2 infections are common among HIV-1-discordant couples.

BACKGROUND: The synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) is well known, but lack of knowledge about the epidemiology of HSV-2 acquisition in HIV-1-discordant couples hampers development of HSV-2 prevention interventions that could reduce HIV-1 transmission. METHODS: HIV-1-discordant couples were enrolled in Nairobi, Kenya, and followed for up to 2 years. HSV-2 status was determined using HerpeSelect HSV-2 ELISA. Correlates of prevalence and incidence were assessed. RESULTS.: Of 469 HIV-1-discordant couples, at baseline, 353 (75.3%) were affected by HSV-2, of which 189 (53.5%) were concordantly HSV-2 seropositive and 164 (46.5%) were HSV-2-discordant. Prevalence was lowest among HIV-1-uninfected men (39.9%) compared to HIV-1-infected women (64.8%), HIV-1-infected men (66.7%), and HIV-1-uninfected women (68.5%). During follow-up, HSV-2 seroincidence was 14.9 per 100 person-years. Incidence was 1.6-fold higher among females compared to males (95% confidence interval [CI], 1.00-2.48) and 2.5-fold higher in HIV-1-infected compared to uninfected women (95% CI, 1.12-5.74). At least 30% of incident HSV-2 infections originated from an outside partner. CONCLUSIONS: The high HSV-2 prevalence and incidence in HIV-1-discordant couples in sub-Saharan Africa suggest HSV-2 treatment and prevention could be an effective targeted strategy to reduce HSV-2 and HIV-1 transmission in this high-risk population.

Cost and Cost-Effectiveness of Distributing HIV Self-Tests within Assisted Partner Services in Western Kenya.

Background: Assisted partner services (APS) is a recommended public health approach to promote HIV testing for sexual partners of individuals diagnosed with HIV. We evaluated the cost and cost-effectiveness of integrating oral HIV self-testing (HIVST) into existing APS programs. Methods: Within the APS-HIVST study conducted in western Kenya (2021-2022), we conducted micro-costing, time-and-motion, and provider surveys to determine incremental HIVST distribution cost (2022 USD). Using a decision tree model, we estimated the incremental cost per new diagnosis (ICND) for HIVST incorporated into APS, compared to APS with provider-delivered testing only. Scenario, parameter and probabilistic sensitivity analyses were conducted to explore influential assumptions. Results: The cost per HIVST distributed within APS was USD 8.97, largest component costs were testing supplies (38%) and personnel (30%). Under conditions of a facility-based testing uptake of <91%, or HIVST utilization rates of <27%, HIVST integration into APS is potentially cost-effective. At a willing-to-pay threshold of USD 1000, the net monetary benefit was sensitive to the effectiveness of HIVST in increasing testing rates, phone call rates, HIVST sensitivity, HIV prevalence, cost of HIVST, space allocation at facilities, and personnel time during facility-based testing. In a best-case scenario, the HIVST option was cheaper by USD 3037 and diagnosed 11 more cases (ICND = 265.82). Conclusions: Implementers and policy makers should ensure that HIVST programs are implemented under conditions that guarantee efficiency by focusing on facilities with low uptake for provider-delivered facility-based testing, while deliberately targeting HIVST utilization among the few likely to benefit from remote testing. Additional measures should focus on minimizing costs relating to personnel and testing supplies.

Implementation and Assessment of the HIV Enhanced Access Testing in the Emergency Department (HEATED) Program in Nairobi, Kenya: A Quasi-Experimental Prospective Study.

Background: Persons seeking emergency injury care are often from underserved key populations (KPs) and priority populations (PPs) for HIV programming. While facility-based HIV Testing Services (HTS) in Kenya are effective, emergency department (ED) delivery is limited, despite the potential to reach underserved persons. Methods: This quasi-experimental prospective study evaluated implementation of the HIV Enhanced Access Testing in Emergency Departments (HEATED) at Kenyatta National Hospital ED in Nairobi, Kenya. The HEATED program was designed using setting specific data and utilizes resource reorganization, services integration and HIV sensitization to promote ED-HTS. KPs included sex workers, gay men, men who have sex with men, transgender persons and persons who inject drugs. PPs included young persons (18-24 years), victims of interpersonal violence, persons with hazardous alcohol use and those never previously HIV tested. Data were obtained from systems-level records, enrolled injured patient participants and healthcare providers. Systems and patient-level data were collected during a pre-implementation period (6 March - 16 April 2023) and post-implementation (period 1, 1 May - 26 June 2023). Additional, systems-level data were collected during a second post-implementation (period 2, 27 June - 20 August 2023). Evaluation analyses were completed across reach, effectiveness, adoption, implementation and maintenance framework domains. Results: All 151 clinical staff were reached through trainings and sensitizations on the HEATED program. Systems-level ED-HTS increased from 16.7% pre-implementation to 23.0% post-implementation periods 1 and 2 (RR=1.31, 95% CI:1.21-1.43; p<0.001) with a 62.9% relative increase in HIV self-test kit provision. Among 605 patient participants, facilities-based HTS increased from 5.7% pre-implementation to 62.3% post-implementation period 1 (RR=11.2, 95%CI:6.9-18.1; p<0.001). There were 440 (72.7%) patient participants identified as KPs (5.6%) and/or PPs (65.3%). For enrolled KPs/PPs, HTS increased from 4.6% pre-implementation to 72.3% post-implementation period 1 (RR=13.8, 95%CI:5.5-28.7, p<0.001). Systems and participant level data demonstrated successful adoption and implementation of the HEATED program. Through 16-weeks post-implementation a significant increase in ED-HTS delivery was maintained as compared to pre-implementation. Conclusions: The HEATED program increased ED-HTS and augmented delivery to KPs/PPs, suggesting that broader implementation could improve HIV services for underserved persons, already in contact with health systems.

Assessment of the HIV Enhanced Access Testing in the Emergency Department (HEATED) program in Nairobi, Kenya: a quasi-experimental prospective study.

BACKGROUND: Persons seeking emergency injury care are often from higher-risk and underserved key populations (KPs) and priority populations (PPs) for HIV programming. While facility-based HIV Testing Services (HTS) in Kenya are effective, emergency department (ED) delivery is limited, despite the potential to reach underserved persons. METHODS: This quasi-experimental prospective study evaluated implementation of the HIV Enhanced Access Testing in Emergency Departments (HEATED) at Kenyatta National Hospital ED in Nairobi, Kenya. The HEATED program was designed as a multi-component intervention employing setting appropriate strategies for HIV care sensitization and integration, task shifting, resource reorganization, linkage advocacy, skills development and education to promote ED-HTS with a focus on higher-risk persons. KPs included sex workers, gay men, men who have sex with men, transgender persons and persons who inject drugs. PPs included young persons (18-24 years), victims of interpersonal violence, persons with hazardous alcohol use and persons never HIV tested. Data were obtained from systems-level records, enrolled injured patient participants and healthcare providers. Systems and patient-level data were collected during a pre-implementation period (6 March - 16 April 2023) and post-implementation (period 1, 1 May - 26 June 2023). Additional, systems-level data were collected during a second post-implementation (period 2, 27 June - 20 August 2023). HTS data were evaluated as facility-based HIV testing (completed in the ED) and distribution of HIV self-tests independently, and aggregated as ED-HTS. Evaluation analyses were completed across reach, effectiveness, adoption, implementation and maintenance framework domains. RESULTS: All 151 clinical staff were reached through trainings and sensitizations on the HEATED program. Systems-level ED-HTS among all presenting patients increased from 16.7% pre-implementation to 23.0% post-implementation periods 1 and 2 (RR = 1.31, 95% CI: 1.21-1.43; p < 0.001). Among 605 enrolled patient participants, facilities-based HTS increased from 5.7% pre-implementation to 62.3% post-implementation period 1 (RR = 11.2, 95%CI: 6.9-18.1; p < 0.001). There were 440 (72.7%) patient participants identified as KPs (5.6%) and/or PPs (65.3%). For enrolled KPs/PPs, facilities-based HTS increased from 4.6% pre-implementation to 72.3% post-implementation period 1 (RR = 13.8, 95%CI: 5.5-28.7, p < 0.001). Systems and participant level data demonstrated successful adoption and implementation of the HEATED program. Through 16 wk post-implementation a significant increase in ED-HTS delivery was maintained as compared to pre-implementation. CONCLUSIONS: The HEATED program increased overall ED-HTS and augmented delivery to KPs/PPs, suggesting that broader implementation could improve HIV services for underserved persons already in contact with health systems.

Effectiveness of HIV self-testing when offered within assisted partner services in Western Kenya (APS-HIVST Study): a cluster randomized controlled trial.

INTRODUCTION: Assisted partner services (APS) is an effective strategy for increasing HIV testing, new diagnosis, and linkage to care among sexual partners of people living with HIV (PLWH). APS can be resource intensive as it requires community tracing to locate each partner named and offer them testing. There is limited evidence for the effectiveness of offering HIV self-testing (HIVST) as an option for partner testing within APS. METHODS: We conducted a cluster randomized controlled trial comparing provider-delivered HIV testing (Standard APS) versus offering partners the option of provider-delivered testing or HIVST (APS+HIVST) at 24 health facilities in Western Kenya. Facilities were randomized 1:1 and we conducted intent-to-treat analyses using Poisson generalized linear mixed models to estimate intervention impact on HIV testing, new HIV diagnoses, and linkage to care. All models accounted for clustering at the clinic level and new diagnoses and linkage models were adjusted for individual-level age, sex, and income a priori. RESULTS: From March to December 2021, 755 index clients received APS and named 5054 unique partners. Among these, 1408 partners reporting a prior HIV diagnosis were not eligible for HIV testing and were excluded from analyses. Of the remaining 3646 partners, 96.9% were successfully contacted for APS and tested for HIV: 2111 (97.9%) of 2157 in the APS+HIVST arm and 1422 (95.5%) of 1489 in the Standard APS arm. In the APS+HIVST arm, 84.6% (1785/2111) tested via HIVST and 15.4% (326/2111) received provider-delivered testing. Overall, 16.7% of the 3533 who tested were newly diagnosed with HIV (APS+HIVST = 357/2111 [16.9%]; Standard APS = 232/1422 [16.3%]). Of the 589 partners who were newly diagnosed, 90.7% were linked to care (APS+HIVST = 309/357 [86.6%]; Standard APS = 225/232 [97.0%]). There were no significant differences between the two arms in HIV testing (relative risk [RR]: 1.02, 95% CI: 0.96-1.10), new HIV diagnoses (adjusted RR [aRR]: 1.03, 95% CI: 0.76-1.39) or linkage to care (aRR: 0.88, 95% CI: 0.74-1.06). CONCLUSIONS: There were no differences between APS+HIVST and Standard APS, demonstrating that integrating HIVST into APS continues to be an effective strategy for identifying PLWH by successfully reaching and HIV testing >95% of elicited partners, newly diagnosing with HIV one in six of those tested, >90% of whom were linked to care. CLINICAL TRIAL NUMBER: NCT04774835.

Providing HIV-assisted partner services to partners of partners in western Kenya: an implementation science study.

INTRODUCTION: Assisted partner services (APS), or exposure notification and HIV testing for sexual partners of persons diagnosed HIV positive (index clients), is recommended by the World Health Organization. Most APS literature focuses on outcomes among index clients and their partners. There is little data on the benefits of providing APS to partners of partners diagnosed with HIV. METHODS: We utilized data from a large-scale APS implementation project across 31 facilities in western Kenya from 2018 to 2022. Females testing HIV positive at facilities were offered APS; those who consented provided contact information for all male sexual partners in the last 3 years. Male partners were notified of their potential HIV exposure and offered HIV testing services (HTS). Males newly testing positive were also offered APS and asked to provide contact information for their female partners in the last 3 years. Female partners of male partners (FPPs) were provided exposure notification and HTS. All participants with HIV were followed up at 12 months post-enrolment to assess linkage-to antiretroviral treatment (ART) and viral suppression. We compared HIV positivity, demographics and linkage outcomes among female index clients and FPPs. RESULTS: Overall, 5708 FPPs were elicited from male partners, of whom 4951 received HTS through APS (87% coverage); 291 FPPs newly tested HIV positive (6% yield), an additional 1743 (35.2%) reported a prior HIV diagnosis, of whom 99% were on ART at baseline. At 12 months follow-up, most FPPs were taking ART (92%) with very few adverse events: <1% reported intimate partner violence or reported relationship dissolution. FPPs were more likely than female index clients to report HIV risk behaviours including no condom use at last sex (45% vs. 30%) and multiple partners (38% vs. 19%). CONCLUSIONS: Providing HIV testing via APS to FPP is a safe and effective strategy to identify newly diagnosed females and achieve high linkage and retention to ART and can be an efficient means of identifying HIV cases in the era of declining HIV incidence. The high proportion of FPPs reporting HIV risk behaviours suggests APS may help interrupt community HIV transmission via increased knowledge of HIV status and linkage to treatment.