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.

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.

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.

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.

[HIV-2 infection in Senegal: virological failures and resistance to antiretroviral drugs (ARVs)]. / Infection à VIH-2 au Sénégal: échecs virologiques et résistances aux antirétroviraux (ARV).

INTRODUCTION: HIV-2, endemic in West Africa, has a natural resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) which makes it difficult to treat it in developing countries. METHODS: We conducted a descriptive, longitudinal, prospective study over the period November 2005-June 2017. Virologic failure has been defined as any viral load greater than 50 copies/ml after 6 months of ARV treatment administered twice. Assays for detecting drug-resistance mutations was performed in the protease-coding region and in the reverse transcriptase-coding region. RESULTS: Data from a total of 110 patients were collected. The patients had a median age of 46 years (ranging from 18 to 67) with a sex-ratio F/M of 2.54. At inclusion, viral load could be assessed in 44% of cases with a median of 935cp/ml (ranging from 17 to 144038). Antiretroviral regimen consisted of a combination of 2 NRTIs and 1IP in 94% of cases. The median follow-up was 1200 days (ranging from 1 to 3840); 94 then 76 patients completed their 12-month and 24-month assessments respectively. At 24-month follow-up, 39 patients had virologic failure, reflecting a prevalence of 39% estimated at 33% at 12-month follow-up and at 11% at 24-month follow-up; NRTIs resistance was observed in 45% of patients, IP resistance in 41% of patients while multi-NRTIs resistance and multi-IP resistance in 30% of patients. CONCLUSION: Currently, there is an urgent need to make available the new therapeutic classes of ARV for second line ART for patients living with HIV-2 with therapeutic failure in resource-limited settings.

Nutrition support for HIV-TB co-infected adults in Senegal, West Africa: A randomized pilot implementation study.

BACKGROUND: Food insecurity can contribute to poor adherence to both tuberculosis treatment and HIV antiretroviral therapy (ART). Interventions that target food insecurity have the potential to increase treatment adherence, improve clinical outcomes, and decrease mortality. The goals of this study were to compare the feasibility, acceptability, and potential impact of implementing two different forms of nutrition support for HIV-TB co-infected adults in the Casamance region of Senegal. METHODS: We conducted a randomized pilot implementation study among HIV-TB co-infected adults initiating treatment for TB (ClinicalTrials.gov Identifier: NCT03711721). Subjects received nutrition support in the form of a local food basket or Ready-to-Use Therapeutic Food (RUTF), distributed on a monthly basis for six months. RESULTS: A total of 178 monthly study encounters were completed by 26 HIV-TB co-infected adults; 14 received food baskets and 12 received RUTF. For both the food basket and RUTF, 100% of subjects obtained the supplement at every study encounter, transferred the supplement from the clinic to their household, and consumed the supplement. The food basket had greater acceptability and was more likely to be shared with members of the household. Adherence to TB treatment and ART exceeded 95%, and all outcomes, including CD4 cell count, hemoglobin, nutritional status, and food security, improved over the study period. All subjects completed TB treatment and were smear negative at treatment completion. The total cost of the local food basket was approximately $0.68 per day versus $0.99 for the RUTF. CONCLUSION: The implementation of nutrition support for HIV-TB co-infected adults in Senegal is feasible and may provide an effective strategy to improve adherence, treatment completion, and clinical outcomes for less than 1 USD per day. Further studies to determine the impact of nutrition support among a larger population of HIV-TB co-infected individuals are indicated.

Traditional healers, HIV outcomes, and mortality among people living with HIV in Senegal, West Africa.

OBJECTIVES: The goals of this study were to determine the frequency of traditional healer use among people living with HIV in Senegal, to identify predictors of traditional healer use, and to determine if traditional healer use is associated with HIV outcomes. DESIGN: Prospective longitudinal study. METHODS: Participants were enrolled from April 2017 to April 2018 in Dakar and Ziguinchor, Senegal. Interviews, clinical evaluations, laboratory analyses, and chart review were conducted. Logistic regression was used to identify sociodemographic predictors of traditional healer use and to determine the associations between HIV-outcomes and use of a traditional healer. Survival analysis was conducted using the Kaplan-Meier method. RESULTS: Data from 157 HIV-positive individuals were included; 34% reported seeking care from a traditional healer. Median follow-up was 224 days (interquartile range 118-339.5). Predictors of traditional healer use included age greater than or equal to 35 years and residence in the Casamance region. HIV-1-infected participants who sought care from a traditional healer had lower baseline CD4 cell counts compared with those who did not (104 versus 208; P = 0.02), and a greater percentage presented with advanced disease (85% versus 62%; P = 0.01). A greater percentage of those who sought care from a traditional healer died (13.2 versus 2.9%; P = 0.03). HIV-1-infected individuals with advanced disease [odds ratio (OR) 3.58, 95% confidence interval (CI) 1.18-10.82], those who were malnourished (OR 3.79, 95% CI 1.63-8.83), and those who died during follow-up (OR 7.26, 95% CI 1.34-39.37) were more likely to have sought care from a traditional healer. CONCLUSION: Traditional healer use is common among people living with HIV in Senegal and is associated with advanced disease and increased mortality. Partnering with traditional healers may be an effective strategy to improve the HIV care cascade and decrease mortality in the region.

Prevalence, predictors, and management of advanced HIV disease among individuals initiating ART in Senegal, West Africa.

BACKGROUND: The WHO guidelines for the management of advanced HIV disease recommend a package of care consisting of rapid initiation of antiretroviral therapy (ART), enhanced screening and diagnosis of tuberculosis (TB) and cryptococcal meningitis, co-trimoxazole prophylaxis, isoniazid preventive therapy (IPT), fluconazole pre-emptive therapy, and adherence support. The goals of this study were to determine the prevalence of advanced HIV disease among individuals initiating ART in Senegal, to identify predictors of advanced disease, and to evaluate adherence to the WHO guidelines. METHODS: This study was conducted among HIV-positive individuals initiating ART in Dakar and Ziguinchor, Senegal. Clinical evaluations, laboratory analyses, questionnaires and chart review were conducted. Logistic regression was used to identify predictors of advanced disease. RESULTS: A total of 198 subjects were enrolled; 70% were female. The majority of subjects (71%) had advanced HIV disease, defined by the WHO as a CD4 count < 200 cells/mm3 or clinical stage 3 or 4. The median CD4 count was 185 cells/mm3. The strongest predictors of advanced disease were age ≥ 35 (OR 5.80, 95%CI 2.35-14.30) and having sought care from a traditional healer (OR 3.86, 95%CI 1.17-12.78). Approximately one third of subjects initiated ART within 7 days of diagnosis. Co-trimoxazole prophylaxis was provided to 65% of subjects with CD4 counts ≤350 cells/mm3 or stage 3 or 4 disease. TB symptom screening was available for 166 subjects; 54% reported TB symptoms. Among those with TB symptoms, 39% underwent diagnostic evaluation. Among those eligible for IPT, one subject received isoniazid. No subjects underwent CrAg screening or received fluconazole to prevent cryptococcal meningitis. CONCLUSIONS: This is the first study to report an association between seeking care from a traditional healer and presentation with WHO defined advanced disease in sub-Saharan Africa. Given the widespread use of traditional healers in sub-Saharan Africa, future studies to further explore this finding are indicated. Although the majority of individuals in this study presented with advanced disease and warranted management according to WHO guidelines, there were numerous missed opportunities to prevent HIV-associated morbidity and mortality. Programmatic evaluation is needed to identify barriers to implementation of the WHO guidelines and enhanced funding for operational research is indicated.

A Trial of a Single-tablet Regimen of Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate for the Initial Treatment of Human Immunodeficiency Virus Type 2 Infection in a Resource-limited Setting: 48-Week Results From Senegal, West Africa.

Background: There is an urgent need for safe and effective antiretroviral therapy (ART) for human immunodeficiency virus type 2 (HIV-2) infection. We undertook the first clinical trial of a single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (E/C/F/TDF) to assess its effectiveness in HIV-2-infected individuals in Senegal, West Africa. Methods: HIV-2-infected, ART-naive adults with World Health Organization stage 3-4 disease or CD4 count <750 cells/µL were eligible for this 48-week, open-label trial. We analyzed HIV-2 viral loads (VL), CD4 counts, clinical and adverse events, mortality, and loss to follow-up. Results: We enrolled 30 subjects who initiated E/C/F/TDF. Twenty-nine subjects completed 48 weeks of follow-up. The majority were female (80%). There were no deaths, no new AIDS-associated clinical events, and 1 loss to follow-up. The median baseline CD4 count was 408 (range, 34-747) cells/µL, which increased by a median 161 (range, 27-547) cells/µL at week 48. Twenty-five subjects had baseline HIV-2 VL of <50 copies/mL of plasma. In those with detectable HIV-2 VL, the median was 41 (range, 10-6135) copies/mL. Using a modified intent-to-treat analysis (US Food and Drug Administration Snapshot method), 28 of 30 (93.3%; 95% confidence interval, 77.9%-99.2%) had viral suppression at 48 weeks. The 1 subject with virologic failure had multidrug-resistant HIV-2 (reverse transcriptase mutation: K65R; integrase mutations: G140S and Q148R) detected at week 48. There were 8 grade 3-4 adverse events; none were deemed study related. Adherence and acceptability were good. Conclusions: Our data suggest that E/C/F/TDF, a once-daily, single-tablet-regimen, is safe, effective, and well tolerated. Our findings support the use of integrase inhibitor-based regimens for HIV-2 treatment. Clinical Trials Registration: NCT02180438.