Evaluation of a novel university-based testing platform to increase access to SARS-CoV-2 testing during the COVID-19 pandemic in a cohort study.

OBJECTIVE: We aimed to evaluate the feasibility and utility of an unsupervised testing mechanism, in which participants pick up a swab kit, self-test (unsupervised) and return the kit to an on-campus drop box, as compared with supervised self-testing at staffed locations. DESIGN: University SARS-CoV-2 testing cohort. SETTING: Husky Coronavirus Testing provided voluntary SARS-CoV-2 testing at a university in Seattle, USA. OUTCOME MEASURES: We computed descriptive statistics to describe the characteristics of the study sample. Adjusted logistic regression implemented via generalised estimating equations was used to estimate the odds of a self-swab being conducted through unsupervised versus supervised testing mechanisms by participant characteristics, including year of study enrolment, pre-Omicron versus post-Omicron time period, age, sex, race, ethnicity, affiliation and symptom status. RESULTS: From September 2021 to July 2022, we received 92 499 supervised and 26 800 unsupervised self-swabs. Among swabs received by the laboratory, the overall error rate for supervised versus unsupervised swabs was 0.3% vs 4%, although this declined to 2% for unsupervised swabs by the spring of the academic year. Results were returned for 92 407 supervised (5% positive) and 25 836 unsupervised (4%) swabs from 26 359 participants. The majority were students (79%), 61% were female and most identified as white (49%) or Asian (34%). The use of unsupervised testing increased during the Omicron wave when testing demand was high and stayed constant in spring 2022 even when testing demand fell. We estimated the odds of using unsupervised versus supervised testing to be significantly greater among those <25 years of age (p<0.001), for Hispanic versus non-Hispanic individuals (OR 1.2, 95% CI 1.0 to 1.3, p=0.01) and lower among individuals symptomatic versus asymptomatic or presymptomatic (0.9, 95% CI 0.8 to 0.9, p<0.001). CONCLUSIONS: Unsupervised swab collection permitted increased testing when demand was high, allowed for access to a broader proportion of the university community and was not associated with a substantial increase in testing errors.

Utilizing a university testing program to estimate relative effectiveness of monovalent COVID-19 mRNA booster vaccine versus two-dose primary series against symptomatic SARS-CoV-2 infection.

Vaccine effectiveness (VE) studies utilizing the test-negative design are typically conducted in clinical settings, rather than community populations, leading to bias in VE estimates against mild disease and limited information on VE in healthy young adults. In a community-based university population, we utilized data from a large SARS-CoV-2 testing program to estimate relative VE of COVID-19 mRNA vaccine primary series and monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection from September 2021 to July 2022. We used the test-negative design and logistic regression implemented via generalized estimating equations adjusted for age, calendar time, prior SARS-CoV-2 infection, and testing frequency (proxy for test-seeking behavior) to estimate relative VE. Analyses included 2,218 test-positive cases (59 % received monovalent booster dose) and 9,615 test-negative controls (62 %) from 9,066 individuals, with median age of 21 years, mostly students (71 %), White (56 %) or Asian (28 %), and with few comorbidities (3 %). More cases (23 %) than controls (6 %) had COVID-19-like illness. Estimated adjusted relative VE of primary series and monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection was 40 % (95 % CI: 33-47 %) during the overall analysis period and 46 % (39-52 %) during the period of Omicron circulation. Relative VE was greater for those without versus those with prior SARS-CoV-2 infection (41 %, 34-48 % versus 33 %, 9 %-52 %, P < 0.001). Relative VE was also greater in the six months after receiving a booster dose (41 %, 33-47 %) compared to more than six months (27 %, 8-42 %), but this difference was not statistically significant (P = 0.06). In this relatively young and healthy adult population, an mRNA monovalent booster dose provided increased protection against symptomatic SARS-CoV-2 infection, overall and with the Omicron variant. University testing programs may be utilized for estimating VE in healthy young adults, a population that is not well-represented by routine VE studies.

Antiviral Activity of Lenacapavir Against HIV-2 Isolates and Drug-resistant HIV-2 Mutants.

The activity of lenacapavir against HIV-1 has been extensively evaluated in vitro, but comparable data for HIV-2 are scarce. We determined the anti-HIV-2 activity of lenacapavir using single-cycle infections of MAGIC-5A cells and multicycle infections of a T cell line. Lenacapavir exhibited low-nanomolar activity against HIV-2, but was 11- to 14-fold less potent against HIV-2 in comparison to HIV-1. Mutations in HIV-2 that confer resistance to other antiretrovirals did not confer cross-resistance to lenacapavir. Although lenacapavir-containing regimens might be considered for appropriate patients with HIV-2, more frequent viral load and/or CD4 testing may be needed to assess clinical response.

Duration of viral infectiousness and correlation with symptoms and diagnostic testing in non-hospitalized adults during acute SARS-CoV-2 infection: A longitudinal cohort study.

BACKGROUND: Guidelines for SARS-CoV-2 have relied on limited data on duration of viral infectiousness and correlation with COVID-19 symptoms and diagnostic testing. METHODS: We enrolled ambulatory adults with acute SARS-CoV-2 infection and performed serial measurements of COVID-19 symptoms, nasal swab viral RNA, nucleocapsid (N) and spike (S) antigens, and replication-competent SARS-CoV-2 by viral growth in culture. We determined average time from symptom onset to a first negative test result and estimated risk of infectiousness, as defined by positive viral growth in culture. RESULTS: Among 95 adults, median [interquartile range] time from symptom onset to first negative test result was 9 [5] days, 13 [6] days, 11 [4] days, and >19 days for S antigen, N antigen, culture growth, and viral RNA by RT-PCR, respectively. Beyond two weeks, virus growth and N antigen titers were rarely positive, while viral RNA remained detectable among half (26/51) of participants tested 21-30 days after symptom onset. Between 6-10 days from symptom onset, N antigen was strongly associated with culture positivity (relative risk=7.61, 95% CI: 3.01-19.22), whereas neither viral RNA nor symptoms were associated with culture positivity. During the 14 days following symptom onset, the presence of N antigen remained strongly associated (adjusted relative risk=7.66, 95% CI: 3.96-14.82) with culture positivity, regardless of COVID-19 symptoms. CONCLUSIONS: Most adults have replication-competent SARS-CoV-2 for 10-14 after symptom onset. N antigen testing is a strong predictor of viral infectiousness and may be a more suitable biomarker, rather than absence of symptoms or viral RNA, to discontinue isolation within two weeks from symptom onset.

Intrinsic resistance of HIV-2 and SIV to the maturation inhibitor GSK2838232.

GSK2838232 (GSK232) is a novel maturation inhibitor that blocks the proteolytic cleavage of HIV-1 Gag at the junction of capsid and spacer peptide 1 (CA/SP1), rendering newly-formed virions non-infectious. To our knowledge, GSK232 has not been tested against HIV-2, and there are limited data regarding the susceptibility of HIV-2 to other HIV-1 maturation inhibitors. To assess the potential utility of GSK232 as an option for HIV-2 treatment, we determined the activity of the compound against a panel of HIV-1, HIV-2, and SIV isolates in culture. GSK232 was highly active against HIV-1 isolates from group M subtypes A, B, C, D, F, and group O, with IC50 values ranging from 0.25-0.92 nM in spreading (multi-cycle) assays and 1.5-2.8 nM in a single cycle of infection. In contrast, HIV-2 isolates from groups A, B, and CRF01_AB, and SIV isolates SIVmac239, SIVmac251, and SIVagm.sab-2, were highly resistant to GSK232. To determine the role of CA/SP1 in the observed phenotypes, we constructed a mutant of HIV-2ROD9 in which the sequence of CA/SP1 was modified to match the corresponding sequence found in HIV-1. The resulting variant was fully susceptible to GSK232 in the single-cycle assay (IC50 = 1.8 nM). Collectively, our data indicate that the HIV-2 and SIV isolates tested in our study are intrinsically resistant to GSK232, and that the determinants of resistance map to CA/SP1. The molecular mechanism(s) responsible for the differential susceptibility of HIV-1 and HIV-2/SIV to GSK232 require further investigation.

Effect of Human Immunodeficiency Virus Infection on Human Papillomavirus Clearance Among Women in Senegal, West Africa.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HPV) is associated with development of invasive cervical cancer. METHODS: Longitudinal data was collected from 174 Senegalese women. We employed marginal Cox proportional hazards models to examine the effect of human immunodeficiency virus (HIV) status (HIV positive vs HIV negative) and HIV type (HIV-1 vs HIV-2 vs dual HIV-1/HIV-2) on clearance of type-specific HPV infection. Analyses were stratified by incident versus prevalent HPV infection. RESULTS: Incident HPV infections in HIV-positive women were less likely to clear than those in HIV-negative women (adjusted hazard ratio [HR] = 0.60; 95% confidence interval [CI], .38-.94). Among HIV-positive women, HIV-2-infected women and HIV-1/2 dually infected women were more likely to clear HPV incident infections than HIV-1-infected women (HR = 1.66; 95% CI, .95-2.92 and HR = 2.17; 95% CI, 1.12-4.22, respectively). Incident HPV infections in HIV-positive women with CD4 cell count ≤500 cells/µL were less likely to clear than those in HIV-positive women with CD4 cell count >500 cells/µL (HR = 0.65; 95% CI, .42-1.01). No significant associations were observed for prevalent HPV infections. CONCLUSIONS: HIV infection reduced the likelihood of clearance of incident HPV infection. Furthermore, among HIV-positive women, low CD4 cell count and dual HIV infection were each associated with reduced likelihood of clearance.

Why does age at HIV infection correlate with set point viral load? An evolutionary hypothesis.

BACKGROUND: Set-point viral load (SPVL) correlates with the age at which people acquire HIV. Although immunosenescence may seem like a parsimonious explanation for this, it does not easily explain the observation that the relationship between age and SPVL attenuates when accounting for source partner SPVL. Here we propose an alternative explanation that encompasses this latter finding: that decreasing risk of acquisition with older age generates a selection bottleneck that selects for more virulent strains with age. METHODS: We adapted a previously published model of HIV transmission and evolution (EvoNetHIV), parameterized here for men who have sex with men (MSM). We conducted a series of simulation experiments that vary seven behavioral or clinical parameters that affect exposure risk as people age. We conducted regressions to determine the mean increase in SPVL per 10-year increase in seroconversion age, with and without source SPVL in the model. RESULTS: All runs generated significant relationships between seroconversion age and SPVL when not including source SPVL. All saw attenuated relationships, most to near 0, with source SPVL included. Four of our behavioral measures (relational duration, age-related homophily, coital frequency, and mean age at relationship formation) had clear effects on this relationship, all in the hypothesized direction. Combining multiple forms of behavioral heterogeneity yielded an increase of 0.056 log10 copies/mL SPVL per 10-year increase in seroconversion age, nearly as large as that seen in two empirical studies of age-SPVL correlations in MSM. CONCLUSION: The higher virulence of HIV among those infected later in life may be partly explained by a combination of selective bottlenecks and behavioral heterogeneity by age. Variation in the strength of this effect across populations may be in part due to different behavioral, epidemiological and clinical conditions, and not require assumptions about differences in patterns of immunosenescence among populations.

Genomic surveillance of SARS-CoV-2 Omicron variants on a university campus.

Novel variants continue to emerge in the SARS-CoV-2 pandemic. University testing programs may provide timely epidemiologic and genomic surveillance data to inform public health responses. We conducted testing from September 2021 to February 2022 in a university population under vaccination and indoor mask mandates. A total of 3,048 of 24,393 individuals tested positive for SARS-CoV-2 by RT-PCR; whole genome sequencing identified 209 Delta and 1,730 Omicron genomes of the 1,939 total sequenced. Compared to Delta, Omicron had a shorter median serial interval between genetically identical, symptomatic infections within households (2 versus 6 days, P = 0.021). Omicron also demonstrated a greater peak reproductive number (2.4 versus 1.8), and a 1.07 (95% confidence interval: 0.58, 1.57; P < 0.0001) higher mean cycle threshold value. Despite near universal vaccination and stringent mitigation measures, Omicron rapidly displaced the Delta variant to become the predominant viral strain and led to a surge in cases in a university population.

Spectrum of Activity of Raltegravir and Dolutegravir Against Novel Treatment-Associated Mutations in HIV-2 Integrase: A Phenotypic Analysis Using an Expanded Panel of Site-Directed Mutants.

BACKGROUND: Integrase inhibitors (INIs) are a key component of antiretroviral therapy for human immunodeficiency virus-1 (HIV-1) and HIV-2 infection. Although INI resistance pathways are well-defined for HIV-1, mutations that emerge in HIV-2 in response to INIs are incompletely characterized. METHODS: We performed systematic searches of GenBank and HIV-2 drug resistance literature to identify treatment-associated mutations for phenotypic evaluation. We then constructed a library of 95 mutants of HIV-2ROD9 that contained single or multiple amino acid changes in the integrase protein. Each variant was tested for susceptibility to raltegravir and dolutegravir using a single-cycle indicator cell assay. RESULTS: We observed extensive cross-resistance between raltegravir and dolutegravir in HIV-2ROD9. HIV-2-specific integrase mutations Q91R, E92A, A153G, and H157Q/S, which have not been previously characterized, significantly increased the half maximum effective concentration (EC50) for raltegravir when introduced into 1 or more mutational backgrounds; mutations E92A/Q, T97A, and G140A/S conferred similar enhancements of dolutegravir resistance. HIV-2ROD9 variants encoding G118R alone, or insertions of residues SREGK or SREGR at position 231, were resistant to both INIs. CONCLUSIONS: Our analysis demonstrates the contributions of novel INI-associated mutations to raltegravir and dolutegravir resistance in HIV-2. These findings should help to improve algorithms for genotypic drug resistance testing in HIV-2-infected individuals.

Food insecurity predicts loss to follow-up among people living with HIV in Senegal, West Africa.

The goals of this study were to assess retention on antiretroviral therapy (ART) and to identify predictors of loss to follow-up (LTFU) among people living with HIV (PLHIV) in Senegal. HIV-positive individuals presenting for initiation of ART in Dakar and Ziguinchor were enrolled and followed for 12 months. Data were collected using interviews, clinical evaluations, laboratory analyses, chart review, and active patient tracing. Of the 207 individuals enrolled, 70% were female, 32% had no formal education, and 28% were severely food insecure. At the end of the follow-up period, 58% were retained on ART, 15% were deceased, 4% had transferred care, 5% had migrated, and 16% were lost to follow-up. Enrollment in Ziguinchor (OR 2.71 [1.01-7.22]) and severe food insecurity (OR 2.55 [1.09-5.96]) were predictive of LTFU. Sex, age, CD4 count, BMI <18.5, country of birth, marital status, number of children, household size, education, consultation with traditional healers, transportation time, and transportation cost were not associated with LTFU. The strongest predictor of severe food insecurity was lack of formal education (OR 2.75 [1.30-5.80]). Addressing the upstream drivers of food insecurity and implementing strategies to enhance food security for PLHIV may be effective approaches to reduce LTFU and strengthen the HIV care cascade in the region.

Resource and infrastructure challenges on the RESIST-2 Trial: an implementation study of drug resistance genotype-based algorithmic ART switches in HIV-2-infected adults in Senegal.

BACKGROUND: Second-line treatment of HIV-2 in resource-limited settings (RLS) is complicated by a lack of controlled trial data, limited availability of HIV-2-active antiretroviral drugs, and inadequate access to drug resistance testing. We conducted an implementation trial of a dried blood spot- (DBS) based, drug resistance genotype-informed antiretroviral therapy (ART) switching algorithm for HIV-2-infected patients in Senegal. METHODS: HIV-2-infected adults initiating or receiving ART through the Senegalese national AIDS program were invited to participate in this single-arm trial. DBS from participants with virologic failure (defined as viral load (VL) > 250 copies/mL after > 6 months on the current ART regimen) were shipped to Seattle for genotypic drug resistance testing. Participants with evidence of drug resistance in protease or reverse transcriptase were switched to new regimens according to a pre-specified algorithm. Participant clinical and immuno-virologic outcomes were assessed, as were implementation challenges. RESULTS: We enrolled 152 participants. Ten were initiating ART. The remainder were ART-experienced, with 91.0% virologically suppressed (< 50 copies/mL). Problems with viral load testing capability resulted in obtaining VL results for only 227 of 613 (37.0%) participant-visits. Six of 115 participants (5.2%) with VL available after > 6 months on current ART regimen experienced virologic failure, with per-protocol genotypic testing attempted. One additional test was performed for a participant with a VL of 222 copies/mL. Genotypes from three participants showed no evidence of major drug resistance mutations, two showed nucleoside reverse transcriptase inhibitor (NRTI) resistance, one showed both NRTI and protease inhibitor resistance, and one test failed. No integrase inhibitor resistance was observed. Five of six successfully-tested participants switched to the correct regimen or received additional adherence counseling according to the algorithm; the sixth was lost to follow-up. Follow-up VL testing was available for two participants; both of these were virally suppressed (< 10 copies/mL). The trial was terminated early due to the COVID-19 pandemic (which prevented further VL and genotypic testing), planned rollout of dolutegravir-based 1st-line ART, and funding. CONCLUSIONS: The RESIST-2 trial demonstrated that a DBS-based genotypic test can be used to help inform second-line ART decisions as part of a programmatic algorithm in RLS, albeit with significant implementation challenges. TRIAL REGISTRATION: ClinicalTrials.gov NCT03394196 . Registered on January 9, 2018.

SARS-CoV-2 Epidemiology on a Public University Campus in Washington State.

BACKGROUND: We aimed to evaluate a testing program to facilitate control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission at a large university and measure spread in the university community using viral genome sequencing. METHODS: Our prospective longitudinal study used remote contactless enrollment, daily mobile symptom and exposure tracking, and self-swab sample collection. Individuals were tested if the participant was exposed to a known SARS-CoV-2-infected person, developed new symptoms, or reported high-risk behavior (such as attending an indoor gathering without masking or social distancing), if a member of a group experiencing an outbreak, or at enrollment. Study participants included students, staff, and faculty at an urban public university during the Autumn quarter of 2020. RESULTS: We enrolled 16 476 individuals, performed 29 783 SARS-CoV-2 tests, and detected 236 infections. Seventy-five percent of positive cases reported at least 1 of the following: symptoms (60.8%), exposure (34.7%), or high-risk behaviors (21.5%). Greek community affiliation was the strongest risk factor for testing positive, and molecular epidemiology results suggest that specific large gatherings were responsible for several outbreaks. CONCLUSIONS: A testing program focused on individuals with symptoms and unvaccinated persons who participate in large campus gatherings may be effective as part of a comprehensive university-wide mitigation strategy to control the spread of SARS-CoV-2.

Impact of Traditional Healers on the HIV Care Cascade in Senegal, West Africa: A Longitudinal Study.

Consultation with traditional healers (THs) is common among people living with HIV in sub-Saharan Africa. We conducted a prospective longitudinal study to determine the association between consultation with THs and HIV outcomes following 12 months of antiretroviral therapy (ART). HIV-infected individuals presenting for care and initiation of ART in Dakar and Ziguinchor, Senegal were eligible for enrollment. Data were collected using interviews, clinical evaluations, laboratory analyses, and chart reviews at enrollment, 6 months after ART initiation, and 12 months after ART initiation. Among the 186 participants, 35.5% consulted a TH. The most common reason for consulting a TH was "mystical" concerns (18%). Those who consulted a TH before ART initiation were more likely to present with a CD4 count < 200 cells/mm3 (44% versus 28%; P = 0.04) and WHO stage 3 or 4 disease (64% versus 46%; P = 0.03), and they were less likely to disclose their HIV status (44% versus 65%; P = 0.04). Those who consulted a TH more than 6 months after ART initiation were more likely to report poor adherence to ART (57% versus 4%; P < 0.01). The strongest predictor of virologic failure was consulting a TH more than 6 months after ART initiation (odd ratio [OR], 7.43; 95% CI, 1.22-45.24). The strongest predictors of mortality were consulting a TH before ART initiation (OR, 3.53; 95% CI, 1.25-9.94) and baseline CD4 count < 200 cells/mm3 (OR, 3.15; 95% CI, 1.12-8.89). Our findings reveal multiple opportunities to strengthen the HIV care cascade through partnerships between THs and biomedical providers. Future studies to evaluate the impact of these strategies on HIV outcomes are warranted.

Risk compensation after HIV-1 vaccination may accelerate viral adaptation and reduce cost-effectiveness: a modeling study.

Pathogen populations can evolve in response to selective pressure from vaccine-induced immune responses. For HIV, models predict that viral adaptation, either via strain replacement or selection on de novo mutation, may rapidly reduce the effectiveness of an HIV vaccine. We hypothesized that behavioral risk compensation after vaccination may accelerate the transmission of vaccine resistant strains, increasing the rate of viral adaptation and leading to a more rapid decline in vaccine effectiveness. To test our hypothesis, we modeled: (a) the impact of risk compensation on rates of HIV adaptation via strain replacement in response to a partially effective vaccine; and (b) the combined impact of risk compensation and viral adaptation on vaccine-mediated epidemic control. We used an agent-based epidemic model that was calibrated to HIV-1 trends in South Africa, and includes demographics, sexual network structure and behavior, and within-host disease dynamics. Our model predicts that risk compensation can increase the rate of HIV viral adaptation in response to a vaccine. In combination, risk compensation and viral adaptation can, under certain scenarios, reverse initial declines in prevalence due to vaccination, and result in HIV prevalence at 15 years equal to or greater than prevalence without a vaccine.

The impact of food insecurity on HIV outcomes in Senegal, West Africa: a prospective longitudinal study.

BACKGROUND: Understanding the impact of food insecurity on HIV outcomes is critical for the development and implementation of effective, evidence-based interventions to address food insecurity and improve the HIV care cascade. We conducted a prospective, longitudinal study to determine the impact of food insecurity on HIV outcomes in Senegal, West Africa. METHODS: HIV-infected individuals presenting for care and initiation of ART through the Senegalese National AIDS program in Dakar and Ziguinchor were eligible for enrollment. Data were collected using interviews, clinical evaluations, laboratory analyses, and chart review at enrollment, month 6, and month 12. Logistic regression was used to determine the association between food insecurity and HIV outcomes. RESULTS: Among the 207 participants in this study, 70% were female and the median age was 37 years. The majority (69%) were food insecure at enrollment, 29% were severely food insecure, and 38% were undernourished. Nearly a third (32%) had no formal education, 23% practiced agriculture, and 40% owned livestock. The median daily food expenditure per person was $0.58. The median round trip transportation time to clinic was 90 min (IQR 30-240). The median cost of transportation to clinic was $1.74. At month 12, 69% were food insecure, 23% were severely food insecure, and 14% were undernourished. At month 12, 43% had not disclosed their HIV status; food insecurity was associated with non-disclosure of HIV-status due to fear of stigmatization and feelings of shame. Severe food insecurity was a strong predictor of loss to follow-up (OR 3.13 [1.08-9.06]) and persistent severe food insecurity was associated with virologic failure (OR 5.14 [1.01-26.29]) and poor adherence to ART 8.00 [1.11-57.57]. Poor nutritional status was associated with poor immunologic recovery (OR 4.24 [1.56-11.47]), virologic failure (OR 3.39 [1.13-10.21]), and death (OR 3.35 [1.40-8.03]). CONCLUSION: Severity and duration of food insecurity are important factors in understanding the relationship between food insecurity and HIV outcomes. Our findings highlight the importance of nutritional status, socioeconomic opportunity, and self-stigmatization in the complex pathway between food insecurity and HIV outcomes. Interdisciplinary, multisectoral efforts are needed to develop and implement effective interventions to address food insecurity among people living with HIV.

Long-term Experience and Outcomes of Programmatic Antiretroviral Therapy for Human Immunodeficiency Virus Type 2 Infection in Senegal, West Africa.

BACKGROUND: Programmatic treatment outcome data for people living with human immunodeficiency virus type 2 (HIV-2) in West Africa, where the virus is most prevalent, are scarce. METHODS: Adults with HIV-2 initiating or receiving antiretroviral therapy (ART) through the Senegalese national AIDS program were invited to participate in this prospective, longitudinal observational cohort study. We analyzed HIV-2 viral loads, CD4 cell counts, antiretroviral drug resistance, loss to follow-up, and mortality. We also examined changes in treatment guidelines over time and assessed progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets for HIV-2. RESULTS: We enrolled 291 participants at 2 sites for 926.0 person-years of follow-up over 13 years. Median follow-up time was 2.2 years per participant. There were 21 deaths reported (7.2%), and 117 individuals (40.2%) were lost to follow-up, including 43 (14.7%) who had an initial visit but never returned for follow-up. CD4 counts and HIV-2 viral suppression (< 50 copies/mL) at enrollment increased over calendar time. Over the study period, 76.7% of plasma viral loads for participants receiving ART were suppressed, and median CD4 gain was 84 cells/µL in participants' first 2 years on study. Since the UNAIDS 90-90-90 strategy was published, 88.1% of viral loads were suppressed. Fifteen percent of patients experienced virologic failure with no known resistance mutations, while 56% had evidence of multiclass drug resistance. CONCLUSIONS: Participants in the Senegalese national AIDS program are initiating ART earlier in the course of disease, and more modern therapeutic regimens have improved outcomes among those receiving therapy. Despite these achievements, HIV-2 treatment remains suboptimal, and significant challenges to improving care remain.

Test-and-treat coverage and HIV virulence evolution among men who have sex with men.

HIV set point viral load (SPVL), the viral load established shortly after initial infection, is a proxy for HIV virulence: higher SPVLs lead to higher risk of transmission and faster disease progression. Three models of test-and-treat scenarios, mainly in heterosexual populations, found that increasing treatment coverage selected for more virulent viruses. We modeled virulence evolution in a population of men who have sex with men (MSM) with increasing test-and-treat coverage. We extended a stochastic, dynamic network model (EvoNetHIV). We varied relationship patterns (MSM vs. heterosexual), HIV transmission models (increasing vs. plateauing probability of transmission at very high viral loads), and treatment roll-out (with explicit testing or fixed intervals between infection and treatment). In scenarios most similar to previous models (longer relational durations and the plateauing transmission function), we replicated trends previously found: increasing treatment coverage led to increased virulence (0.12 log10 increase in mean population SPVL between 20% and 100% treatment coverage). In scenarios reflecting MSM behavioral data using the increasing transmission function, increasing treatment coverage selected for viruses with lower virulence (0.16 log10 decrease in mean population SPVL between 20% and 100% treatment coverage). These findings emphasize the impact of sexual network conditions and transmission function details on predicted epidemiological and evolutionary outcomes. Varying these features creates very different evolutionary environments, which in turn lead to opposite effects in mean population SPVL evolution. Our results suggest that, under some realistic conditions, effective test-and-treat strategies may not face the previously reported tradeoff in which increasing coverage leads to evolution of greater virulence. This suggests instead that a virtuous cycle of increasing treatment coverage and diminishing virulence is possible.

HIV-2 Drug Resistance Genotyping from Dried Blood Spots.

The treatment of HIV-2 in resource-limited settings (RLS) is complicated by the limited availability of HIV-2-active antiretroviral drugs and inadequate access to HIV-2 viral load and drug resistance testing. Dried blood spots (DBS)-based drug resistance testing, widely studied for HIV-1, has not been reported for HIV-2 and could present an opportunity to improve care for HIV-2-infected individuals. We selected 150 DBS specimens from ongoing studies of antiretroviral therapy (ART) for HIV-2 infection in Senegal and subjected them to genotypic drug resistance testing. Total nucleic acid was extracted from DBS, reverse transcribed, PCR amplified, and analyzed by population-based Sanger sequencing, and major drug resistance-associated mutations (RAM) were identified. Parallel samples from plasma and peripheral blood mononuclear cells (PBMC) were also genotyped. We obtained 58 protease/reverse transcriptase genotypes. Plasma viral load was significantly correlated with genotyping success (P < 0.001); DBS samples with corresponding plasma viral load >250 copies/ml had a success rate of 86.8%. In paired DBS-plasma genotypes, 83.8% of RAM found in plasma were also found in DBS, and replicate DBS genotyping revealed that a single test detected 86.7% of known RAM. These findings demonstrate that DBS-based genotypic drug resistance testing for HIV-2 is feasible and can be deployed in RLS with limited infrastructure.

Uptake, retention, and outcomes in a demonstration project of pre-exposure prophylaxis among female sex workers in public health centers in Senegal.

The Senegal pre-exposure prophylaxis (PrEP) Demonstration Project was an open-label cohort study assessing the delivery of daily oral PrEP to HIV-negative female sex workers (FSWs) in four Ministry of Health (MoH)-run clinics in Dakar, Senegal. We assessed uptake, retention in care, and adherence over up to 12 months of follow-up as well as HIV infection rates. Between July and November 2015, 350 individuals were approached and 324 (92.6%) were preliminarily eligible. Uptake was high, with 82.4% of eligible participants choosing to enroll and take PrEP. The mean age of those enrolled was 37.7 years (SD = 8.7), and approximately half had not attended school (41.2%). Among the 267 participants who were prescribed PrEP, 79.9 and 73.4% were retained in PrEP care at 6 and 12 months, respectively. Older age among FSWs was found to be the only significant predictor of lower discontinuation. We did not find significant differences in retention by site, education, condom use, or HIV risk perception. There were no new HIV infections at follow-up. Our results showed evidence of high interest in PrEP and very good PrEP retention rates among FSWs at 12-month follow-up when offered in MoH-run clinics, with older age as the only significant predictor of higher PrEP retention. This highlights the role that these clinics can play in expanding PrEP access nationwide.