Toward a New Paradigm of North-South and South-South Partnerships for Pandemic Preparedness: Lessons Learned from COVID-19 and Other Outbreaks.

COVID-19 underscores the need to reimagine North-South partnerships and redefine best practices for building public health and research capacity to address emergent health threats and pandemic preparedness in low- and-middle income countries (LMICs). Historically, outbreak and emergency responses have failed to ensure that the Global South has the autonomy and capacity to respond to public health threats in a timely and equitable manner. The COVID-19 response, however, has demonstrated that innovations and solutions in the Global South can not only fill resource and capacity gaps in LMICs but can also provide solutions to challenges globally. These innovations offer valuable lessons about strengthening local manufacturing capacity to produce essential diagnostic, treatment, and prevention tools; implementing high-quality research studies; expanding laboratory and research capacity; and promoting effective cooperation and governance. We discuss specific examples of capacity-building from Rwanda, South Africa, and Senegal. To fulfill promises made to the Global South during the COVID-19 pandemic, restore and resume health service delivery, and effectively prevent and respond to the next health threat, we need to prioritize equitable access to local manufacturing of basic health tools while building health systems capacities in the Global South.

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.

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.

Medicine donation programmes supporting the global drive to end the burden of neglected tropical diseases.

Neglected tropical diseases (NTDs) are targeted for global control or elimination. Recognising that the populations most in need of medicines to target NTDs are those least able to support and sustain them financially, the pharmaceutical industry created mechanisms for donating medicines and expertise to affected countries through partnerships with the WHO, development agencies, non-governmental organisations and philanthropic donors. In the last 30 y, companies have established programmes to donate 17 different medicines to overcome the burden of NTDs. Billions of tablets, capsules, intravenous and oral solutions have been donated, along with the manufacturing, supply chains and research necessary to support these efforts. Industry engagement has stimulated other donors to support NTDs with funds and oversight so that the 'heath benefit' return on investment in these programmes is truly a 'best value in public health'. Many current donations are 'open-ended', promising support as long as necessary to achieve defined health targets. Extraordinary global health advances have been made in filariasis, onchocerciasis, trachoma, trypanosomiasis, leishmaniasis, schistosomiasis, intestinal parasites and others; and these advances are taking place in the context of strengthening health systems and meeting the global development goals espoused by the WHO. The pharmaceutical manufacturers, already strong collaborators in initiating or supporting these disease-targeted programmes, have committed to continuing their partnership roles in striving to meet the targets of the WHO's new NTD roadmap to 2030.

Pathology of Senegalese breast cancers.

INTRODUCTION: Breast cancer is among the most common cancers among women in most of Africa. However, features of histologically confirmed breast cancers presenting in specific regional populations is limited. Our study describes the clinic-pathologic features of invasive breast cancer diagnosed in women undergoing biopsy for a clinically apparent mass in Senegal, West Africa. METHODS: A prospective cohort of 522 Senegalese women presenting consecutively to Dantec Hospital (University of Dakar Tumor Institute) with a breast mass were included in the study cohort. Demographic data was collected by survey and 197 (37.7%) core needle biopsy-confirmed invasive breast cancers available for review were subsequently centrally reviewed at the University of Washington in Seattle to further to characterize the pathologic features and to perform immunohistochemistry for ER/PR and HER2. RESULTS: Seventy six (76.1%) of the 522 Senegalese women presenting for biopsy of a clinically apparent breast mass were diagnosed with invasive breast cancer. The average age of a woman with invasive cancer was 46 years old, and most (83%) presented with Stage III or IV disease. The predominant histologic subtype among the 197 biopsy-confirmed cancers was invasive ductal carcinoma (98%), with few cases of invasive lobular carcinoma (2%). Cancers were classified into four clinically relevant treatment IHC groups by combined ER/PR status and HER2 status as follows: ER-/PR-, HER2- (n=92; 46.7%), ER-/PR-, HER2+ (n=20; 10.1%), ER+/PR+, HER2- (n=76; 38.6%) and ER+/PR+, HER2+ (n=9; 4.6%). Age at time of diagnosis was similar between these four subgroups although more HER2 positive cases were pre-menopausal (p=0.05). Stage of disease at presentation differed by IHC group (p=0.008), with HER2+ cancers significantly more likely to present with stage IV disease than other IHC groups, including ER-/PR-, HER2-. There were no significant differences between groups by age group, ethnicity, place of residence or birth, or parity. CONCLUSION: Our analysis of breast cancer cases in Senegal shows a distribution of clinically relevant IHC groups like that seen in the few prior studies of breast cancer in West Africa, with higher frequencies of triple negative cancers than in most United States and European populations. Mean age at presentation, delayed presentation, and genetic/regional risk factors likely influence these differences. A better understanding of the frequencies of the pathologic features of breast cancers in the West African population may help guide future genetic studies as well as appropriate clinical management of breast cancer in these populations.

[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.

Correction: Increasing prevalence of hypertension among HIV-positive and negative adults in Senegal, West Africa, 1994-2015.

[This corrects the article DOI: 10.1371/journal.pone.0208635.].

Female genital mutilation and noninvasive cervical abnormalities and invasive cervical cancer in Senegal, West Africa: A retrospective study.

Female genital mutilation or cutting (FGM/C) is a traditional practice that affects a significant portion of women in sub-Saharan Africa, Egypt, areas of the Middle East and some countries in Asia. While clinical and epidemiological studies have established a close association between inflammation and carcinogenesis, particularly in epithelial cancers, the relationship between FGM/C and cervical cancer is not well known. We performed a secondary analysis using combined data from six research studies conducted in and around Dakar, Senegal from 1994 to 2012. Study subjects included both asymptomatic women who presented to outpatient clinics but were screened for cervical cancer, and women with cancer symptoms who were referred for cervical cancer treatment. We used unconditional logistic regression to estimate adjusted pooled odds ratios (ORs) and 95% confidence intervals (CI) for associations between FGM/C and (1) Invasive cervical cancer (ICC) and (2) noninvasive cervical abnormalities. After adjusting for confounding, women with ICC were 2.50 times more likely to have undergone FGM/C than women without cervical abnormalities (95% CI, 1.28-4.91). Restricting to HPV-positive women increased the strength of the association (OR = 4.23; 95% CI 1.73-10.32). No significant associations between FGM/C and noninvasive cervical abnormalities were observed, except in commercial sex workers with FGM/C (OR = 2.01; 95% CI 1.19-3.40). The potential increased risk for ICC suggested by our study warrants further examination. Study results may impact cancer prevention efforts in populations where FGM/C is practiced and draw awareness to the additional health risks associated with FGM/C.

ART initiation in an outpatient treatment center in Dakar, Senegal: A retrospective cohort analysis (1998-2015).

OBJECTIVE: To examine how patient characteristics combined with ART eligibility expansions affect the initiation of antiretroviral therapy (ART) among eligible patients attending a referral center in Senegal from 1998 to 2015. METHODS: This is a retrospective observational study carried out at the outpatient treatment Centre (Centre de Traitement Ambulatoire) in Dakar, Senegal, based on computerized medical records, gathered from 1998 to 2015, of ART-naïve patients over 15 years of age. ART eligibility was defined as (CD4 count below 200) or as (WHO stage 4) or as (WHO stage 3 with (CD4 count below 350 or with unavailable CD4 count)) in 1998-2010; as (CD4 count below 350) or as (WHO stage 3 or 4) in 2011-2013; as (CD4 count below 500) or as (WHO stage 3 or 4) in 2014-2015. Four periods were defined according to ART eligibility expansions and Senegal's HIV care history: 1998-2003 (P 1), 2004-2010 (P 2), 2011-2013 (P3), and 2014-2015 (P4). Patients were expected to participate financially in their treatment during the first period (P1). RESULTS: A total of 3651 patient records were included. The median patient age was 40 years (IQR: 32-48). Women represented 56% of the population. The median CD4 count was 183 cells/mm3. Overall, 53% of patients had CD4 < 200 cells/mm3 at entry. This proportion reached 45% in 2014-2015. 2535 patients (69%) were eligible for therapy, including 1503 (41%) who started ART. The proportion of treated patients among those who were eligible at entry or later increased steadily from 25%, 47%, 75% to 82% in the four periods, respectively. The median time to treatment decreased from 5.6 months (IQR: 3-11) in P1 to 0.8 months (IQR: 0-2) in P4. Eligible patients with more advanced disease (CD4<200 cells/mm3 and/or clinical stage 3 or 4) were more likely to be ART initiated than those with CD4≥200 cells/mm3 and/or clinical stage 1 or 2 at each stage of ART eligibility expansion. CONCLUSION: ART eligibility expansions were marked by a sharp increase in the proportion of eligible patients initiating treatment. These results show that in terms of management, the target of "Test and Treat" can be easily reached but that HIV testing will remain a key element to improve treatment success, as illustrated by the high proportion of people with advanced stage of infection at the time of ART initiation.

HIV and the dual burden of malnutrition in Senegal, 1994-2012.

The aims of this study were to determine the nutritional status of HIV-positive versus HIV-negative adults in Senegal and to identify predictors of nutritional status among people living with HIV (PLHIV). We conducted a retrospective study using data from individuals enrolled in previous studies in Senegal. Undernutrition was defined as body mass index (BMI) <18.5 and overnutrition was defined as BMI ≥25.0. Subcategories of overnutrition were overweight (defined as BMI 25.0-29.9) and obesity (BMI ≥30.0). Predictors of nutritional status were identified using multinomial logistic regression. Data from 2448 adults were included; 1471 (60%) were HIV positive. Among HIV-negative individuals, the prevalence of undernutrition decreased from 23% in 1994-1999 to 5% in 2006-2012, while the prevalence of overnutrition increased from 19 to 55%. Among PLHIV, undernutrition decreased from 52 to 37% and overnutrition increased from 10 to 15%. Women had greater odds of obesity (odds ratio [OR] 11.4; p < 0.01). Among HIV-positive women, undernutrition was associated with WHO stage 3 or 4 and CD4 cell count <200; antiretroviral therapy (ART) and education were protective. Obesity was associated with age > 35 years, commercial sex work, and alcohol use. Among HIV-positive men, WHO stage 3 or 4 and CD4 cell count <200 were predictive of undernutrition; ART was protective. Our study highlights the need for the integration of nutrition interventions into HIV programs in Senegal and suggests that for nutrition programs to be most effective, strategies may need to differ when targeting men versus women. Furthermore, improving access to education and focusing on women for nutrition interventions could be of particularly high impact at the household level.

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.

Increasing prevalence of hypertension among HIV-positive and negative adults in Senegal, West Africa, 1994-2015.

BACKGROUND: Non-communicable diseases, including hypertension (HTN), are increasingly recognized as important causes of morbidity and mortality among people living with HIV (PLHIV) in resource-limited settings. The goals of this study were to determine the prevalence of HTN among PLHIV in Senegal over time and to identify predictors of HTN among HIV-positive versus HIV-negative adults. METHODS: We conducted a retrospective study using data from individuals enrolled in previous studies in Senegal from 1994-2015. Blood pressure (BP) measurements taken during study visits were used for analysis. HTN was defined as systolic BP≥140 or diastolic BP≥90. We used logistic regression to identify predictors of HTN. RESULTS: We analyzed data from 2848 adults (1687 HIV-positive, 1161 HIV-negative). Among PLHIV, the prevalence of HTN increased from 11% during 1994-1999 to 22% during 2010-2015. Among HIV-negative individuals, the prevalence of HTN increased from 16% to 32%. Among both groups, the odds of HTN more than doubled from 1994-1999 to 2010-2015 (HIV-positive OR 2·4, 95% CI 1·1-5·0; HIV-negative OR 2·6, 95% CI 1·5-4·6). One quarter of all individuals with HTN had stage 2 HTN. The strongest risk factor for HTN was obesity (HIV-positive OR 3·2, 95% CI 1·7-5·8; p<0·01; HIV-negative OR 7·8, 95% CI 4·5-13·6; p<0·01). Male sex and age ≥50 were also predictive of HTN among both groups. Among HIV-positive subjects, WHO stage 1 or 2 disease was predictive of HTN and among HIV-negative subjects, having no formal education was predictive. CONCLUSION: Over the past 20 years, the prevalence of HTN has doubled among both HIV-positive and HIV-negative adults in Senegal. Our study indicates that there is an increasing need for the integration of chronic disease management into HIV programs in Senegal. Furthermore, our findings highlight the need for enhanced prevention, recognition, and management of non-communicable diseases, including hypertension and obesity, among both HIV-positive and HIV-negative individuals in Senegal.

Improving antiretroviral therapy adherence in resource-limited settings at scale: a discussion of interventions and recommendations.

Introduction: Successful population-level antiretroviral therapy (ART) adherence will be necessary to realize both the clinical and prevention benefits of antiretroviral scale-up and, ultimately, the end of AIDS. Although many people living with HIV are adhering well, others struggle and most are likely to experience challenges in adherence that may threaten virologic suppression at some point during lifelong therapy. Despite the importance of ART adherence, supportive interventions have generally not been implemented at scale. The objective of this review is to summarize the recommendations of clinical, research, and public health experts for scalable ART adherence interventions in resource-limited settings. Methods: In July 2015, the Bill and Melinda Gates Foundation convened a meeting to discuss the most promising ART adherence interventions for use at scale in resource-limited settings. This article summarizes that discussion with recent updates. It is not a systematic review, but rather provides practical considerations for programme implementation based on evidence from individual studies, systematic reviews, meta-analyses, and the World Health Organization Consolidated Guidelines for HIV, which include evidence from randomized controlled trials in low- and middle-income countries. Interventions are categorized broadly as education and counselling; information and communication technology-enhanced solutions; healthcare delivery restructuring; and economic incentives and social protection interventions. Each category is discussed, including descriptions of interventions, current evidence for effectiveness, and what appears promising for the near future. Approaches to intervention implementation and impact assessment are then described. Results and discussion: The evidence base is promising for currently available, effective, and scalable ART adherence interventions for resource-limited settings. Numerous interventions build on existing health care infrastructure and leverage available resources. Those most widely studied and implemented to date involve peer counselling, adherence clubs, and short message service (SMS). Many additional interventions could have an important impact on ART adherence with further development, including standardized counselling through multi-media technology, electronic dose monitoring, decentralized and differentiated models of care, and livelihood interventions. Optimal targeting and tailoring of interventions will require improved adherence measurement. Conclusions: The opportunity exists today to address and resolve many of the challenges to effective ART adherence, so that they do not limit the potential of ART to help bring about the end of AIDS.

A Comparison of the Natural History of HPV Infection and Cervical Abnormalities among HIV-Positive and HIV-Negative Women in Senegal, Africa.

Background: There is evidence of an interaction between HIV and human papillomavirus (HPV) resulting in increased HPV-associated morbidity and cancer mortality among HIV-positive women. This study aims to determine how the natural history of cervical HPV infection differs by HIV status.Methods: A total of 1,320 women (47% were positive for HIV-1 and/or HIV-2) were followed for an average of two years in Senegal, West Africa between 1994 and 2010. Cytology (with a sub-sample of histology) and HPV DNA testing were performed at approximately 4-month intervals yielding data from over 7,900 clinic visits. Competing risk modeling was used to estimate rates for transitioning between three clinically relevant natural history stages: Normal, HPV, and HSIL (high-grade squamous intraepithelial lesions). Among HIV-positive women, exploratory univariate analyses were conducted examining the impact of HPV type, infection with multiple HPV types, HIV type, CD4+ count, and age.Results: HIV-positive women had higher rates of progression and lower rates of regression compared with HIV-negative women (i.e., adverse transitions). HIV-positive women had a 2.55 [95% confidence interval (CI), 1.69-3.86; P < 0.0001] times higher rate of progression from HPV to HSIL than HIV-negative women (with 24-month absolute risks of 0.18 and 0.07, respectively). Among HIV-positive women, HPV-16/18 infection and CD4+ count <200/mm3 were associated with adverse transitions.Conclusions: Adverse HIV effects persist throughout HPV natural history stages.Impact: In the limited-resource setting of sub-Saharan Africa where cervical cancer screening is not widely available, the high-risk population of HIV-positive women may be ideal for targeted screening. Cancer Epidemiol Biomarkers Prev; 26(6); 886-94. ©2017 AACR.

Cost Effectiveness of Potential ART Adherence Monitoring Interventions in Sub-Saharan Africa.

BACKGROUND: Interventions based around objective measurement of adherence to antiretroviral drugs for HIV have potential to improve adherence and to enable differentiation of care such that clinical visits are reduced in those with high adherence. It would be useful to understand the approximate upper limit of cost that could be considered for such interventions of a given effectiveness in order to be cost effective. Such information can guide whether to implement an intervention in the light of a trial showing a certain effectiveness and cost. METHODS: An individual-based model, calibrated to Zimbabwe, which incorporates effects of adherence and resistance to antiretroviral therapy, was used to model the potential impact of adherence monitoring-based interventions on viral suppression, death rates, disability adjusted life years and costs. Potential component effects of the intervention were: enhanced average adherence when on ART, reduced risk of ART discontinuation, and reduced risk of resistance acquisition. We considered a situation in which viral load monitoring is not available and one in which it is. In the former case, it was assumed that care would be differentiated based on the adherence level, with fewer clinic visits in those demonstrated to have high adherence. In the latter case, care was assumed to be primarily differentiated according to viral load level. The maximum intervention cost required to be cost effective was calculated based on a cost effectiveness threshold of $500 per DALY averted. FINDINGS: In the absence of viral load monitoring, an adherence monitoring-based intervention which results in a durable 6% increase in the proportion of ART experienced people with viral load < 1000 cps/mL was cost effective if it cost up to $50 per person-year on ART, mainly driven by the cost savings of differentiation of care. In the presence of viral load monitoring availability, an intervention with a similar effect on viral load suppression was cost-effective when costing $23-$32 per year, depending on whether the adherence intervention is used to reduce the level of need for viral load measurement. CONCLUSION: The cost thresholds identified suggest that there is clear scope for adherence monitoring-based interventions to provide net population health gain, with potential cost-effective use in situations where viral load monitoring is or is not available. Our results guide the implementation of future adherence monitoring interventions found in randomized trials to have health benefit.

Accelerating the Uptake and Timing of Antiretroviral Therapy Initiation in Sub-Saharan Africa: An Operations Research Agenda.

Sydney Rosen and colleagues describe an operations research agenda to accelerating uptake of HIV treatment initiation.

Daily consumption of ready-to-use peanut-based therapeutic food increased fat free mass, improved anemic status but has no impact on the zinc status of people living with HIV/AIDS: a randomized controlled trial.

BACKGROUND: Food insecurity in sub-Saharan Africa and malnutrition constitute the main obstacles for successful treatment of people living with HIV/AIDS (PLWH). The aim of this study was to assess the effect of consuming daily 100 g RUTF (ready-to-use therapeutic food) as supplement, on body composition, anemia and zinc status of hospitalized PLWH in Senegal. METHODS: A Controlled clinical trial was conducted in 65 PLWH randomly allocated to receive either standard hospital diet alone (Control group: n = 33), or the standard diet supplemented with 100 g RUTF/day (RUTF group: n = 32). Supplementation was continued at home during 9 weeks. Individual dietary intakes were measured and compared to the Recommended Dietary Allowances. Body composition was determined using Bio-Impedance Analysis. Hemoglobin was measured by HemoCue and plasma zinc (PZ) concentration by atomic absorption spectrometry. PZ was adjusted to infection (CRP and α1-AGP). All measures were conducted on admission, discharge and after 9 weeks home-based follow up. RESULTS: 34 and 24% of the patients in RUTF and Control groups were suffering from severe malnutrition (BMI < 16 kg/m(2)), respectively. In both groups, more than 90% were anemic and zinc deficiency affected over 50% of the patients. Food consumed by the Control group represented 75, 14 and 55% of their daily recommended intake (DRI) of energy, iron and zinc, respectively. When 100 g of RUTF was consumed with the standard diet, the DRI of energy and zinc were 100% covered (2147 kcal, 10.4 mg, respectively), but not iron (2.9 mg). After 9 weeks of supplementation, body weight, and fat-free mass increased significantly by +11% (p = 0.033), and +11.8% (p = 0.033) in the RUTF group, but not in the Control group, while percentage body fat was comparable between groups (p = 0.888). In the RUTF group, fat free mass gain is higher in the patients on ART (+11.7%, n = 14; p = 0.0001) than in those without ART (+6.2%, n = 6; p = 0.032). Anemia decreased significantly with the supplementation, but zinc status, measured using plasma zinc concentration, remained unchanged. CONCLUSION: Improving PLWH' diet with 100 g RUTF for a long period has a positive impact on muscle mass and anemia but not on the zinc status of the patients. TRIAL NUMBER: NCT02433743, registered 29 April 2015.