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Purpose: Men in Botswana present with more advanced cancer than women, leading to poorer outcomes. We sought to explain sex-specific differences in time to and stage at treatment initiation. Methods: Cancer patients who initiated oncology treatment between October 2010 and June 2017 were recruited at four oncology centers in Botswana. Primary outcomes were time from first visit with cancer symptom to treatment initiation, and advanced cancer (stage III/IV). Sociodemographic and clinical covariates were obtained retrospectively through interviews and medical record review. We used accelerated failure time and logistic models to estimate standardized sex differences in treatment initiation time and risk differences for presentation with advanced stage. Results were stratified by cancer type (breast, cervix, non-Hodgkin's lymphoma, anogenital, head and neck, esophageal, other). Results: 1886 participants (70% female) were included. After covariate adjustment, men experienced longer excess time from first presentation to treatment initiation (8.4 months) than women (7.0 months) for all cancers combined (1.4 months, 95% CI: 0.30, 2.5). In analysis stratified by cancer type, we only found evidence of a sex disparity (Men: 8.2; Women: 6.8 months) among patients with other, non-common cancers (1.4 months, 95% CI: 0.01, 2.8). Men experienced an increased risk of advanced stage (Men: 67%; Women: 60%; aRD: 6.7%, 95% CI: -1.7%, 15.1%) for all cancers combined, but this disparity was only statistically significant among patients with anogenital cancers (Men: 72%; Women: 50%; aRD: 22.0%, 95% CI: 0.5%, 43.5%). Conclusions: Accounting for the types of cancers experienced by men and women strongly attenuated disparities in time to treatment initiation and stage. Higher incidence of rarer cancers among men could explain these disparities. [ABSTRACT FROM AUTHOR]

Background: Cancer incidence is increasing in Africa, and the majority of patients are diagnosed with advanced disease, limiting treatment options and survival. We sought to understand care patterns and factors contributing to delayed diagnosis and treatment initiation among patients with cancer in Botswana. Patients and Methods: We recruited 20 patients who were enrolled in a prospective cancer cohort in Botswana to a qualitative substudy that explored cancer care pathways and factors affecting cancer care access and quality. We conducted an in‐depth interview with each participant between October 2014 and January 2015, using a a structured interview guide with questions about initial cancer symptoms, previous consultations, diagnosis, and care pathways. Medical records were used to confirm dates or treatment details when needed. Results: Individual and interpersonal factors such as cancer awareness and social support facilitated care‐seeking behaviors. However, patients experienced multiple delays in diagnosis and treatment because of provider and health system barriers. Health system factors, such as misdiagnosis, understaffed facilities, poor referral communication and scheduling, and inadequate laboratory reporting systems, affected access to and quality of cancer care. Conclusion: These findings highlight the need for interventions at the patient, provider, and health system levels to improve cancer care quality and outcomes in Botswana. Results also suggest that widespread cancer education has potential to promote early diagnosis through family and community networks. Identified barriers and facilitators suggest that interventions to improve community education and access to diagnostic technologies could help improve cancer outcomes in this setting. Implications for Practice: The majority (54%) of patients with cancer in Botswana present with advanced‐stage cancer despite universal access to free health care, limiting the options for treatment and decreasing the likelihood of positive treatment outcomes. To reduce time from symptom onset to cancer treatment initiation, causes of delay in cancer care trajectories must be identified. The narratives of the patients interviewed for this study give insight into psychosocial factors, outlooks on disease, lower‐level provider delays, and health system barriers that contribute to substantial delays for patients with cancer in Botswana. Identification of problems and barriers is essential for development of effective interventions to mitigate these factors, in order to improve cancer outcomes in this population. The cancer burden in low‐and middle‐income countries (LMIC) is significant and is increasing. The objective of this qualitative study was to explore care‐seeking patterns and identify factors contributing to delayed cancer diagnosis and treatment among cancer patients in Botswana. [ABSTRACT FROM AUTHOR]

Background: Botswana is close to reaching the UNAIDS “90-90-90” HIV testing, antiretroviral treatment (ART), and viral suppression goals. We sought to determine HIV incidence in this setting with both high HIV prevalence and high ART coverage. Methods: We used a cross-sectional approach to assessing HIV incidence. A random, population-based sample of adults age 16–64 years was enrolled in 30 rural and peri-urban communities as part of the Botswana Combination Prevention Project (BCPP), from October 2013 –November 2015. Data and samples from the baseline household survey were used to estimate cross-sectional HIV incidence, following an algorithm that combined Limiting-Antigen Avidity Assay (LAg-Avidity EIA), ART status (documented or by testing ARV drugs in plasma) and HIV-1 RNA load. The LAg-Avidity EIA cut-off normalized optical density (ODn) was set at 1.5. The HIV-1 RNA cut-off was set at 400 copies/mL. For estimation purposes, the Mean Duration of Recent Infection was 130 days and the False Recent Rate (FRR) was evaluated at values of either 0 or 0.39%. Results: Among 12,610 individuals participating in the baseline household survey, HIV status was available for 12,570 participants and 3,596 of them were HIV positive. LAg-Avidity EIA data was generated for 3,581 (99.6%) of HIV-positive participants. Of 326 participants with ODn ≤1.5, 278 individuals were receiving ART verified through documentation and were considered to represent longstanding HIV infections. Among the remaining 48 participants who reported no use of ART, 14 had an HIV-1 RNA load ≤400 copies/mL (including 3 participants with ARVs in plasma) and were excluded, as potential elite/viremic controllers or undisclosed ART. Thus, 34 LAg-Avidity-EIA-recent, ARV-naïve individuals with detectable HIV-1 RNA (>400 copies/mL) were classified as individuals with recent HIV infections. The annualized HIV incidence among 16–64 year old adults was estimated at 1.06% (95% CI 0.68–1.45%) with zero FRR, and at 0.64% (95% CI 0.24–1.04%) using a previously defined FRR of 0.39%. Within a subset of younger individuals 16–49 years old, the annualized HIV incidence was estimated at 1.29% (95% CI 0.82–1.77%) with zero FRR, and at 0.90% (95% CI 0.42–1.38%) with FRR set to 0.39%. Conclusions: Using a cross-sectional estimate of HIV incidence from 2013–2015, we found that at the time of near achievement of the UNAIDS 90-90-90 targets, ~1% of adults (age 16–64 years) in Botswana’s rural and peri-urban communities became HIV infected annually. [ABSTRACT FROM AUTHOR]

Purpose: Botswana has a high prevalence of HIV infection. Currently, there are few data regarding the sociodemographic factors, clinical characteristics, and outcomes of non-Hodgkin lymphoma (NHL)--an AIDS-defining cancer--in the country. Patients and Methods: This study used a prospective cancer registry to identify patients with a new diagnosis of NHL reporting for specialty cancer care at three hospitals in Botswana between October 2010 and August 2016. Treatment patterns and clinical outcomes were analyzed. Results: One hundred four patients with a new diagnosis of NHL were enrolled in this study, 72% of whom had HIV infection. Compared with patients not infected with HIV, patients infected with HIV were younger (median age, 53.9 v 39.1 years; P = .001) and more likely to present with an aggressive subtype of NHL (65.5% v 84.0%; P = .008). All patients infected with HIV received combined antiretroviral therapy throughout the course of the study, and similar chemotherapeutic regimens were recommended for all patients, regardless of subtype or HIV status (six to eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone; or cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab). There was no difference in 1-year mortality among patients not infected with HIV and patients infected with HIV (unadjusted analysis, 52.9% v 37.1%; hazard ratio [HR], 0.73; P = .33; adjusted analysis, HR, 0.57; P = .14). However, when compared with a cohort of patients in the United States matched by subtype, stage, age, sex, and race, patients in Botswana fared worse (1-year mortality, 22.8% v 46.3%; HR, 1.89; P = .001). Conclusion: Among patients with NHL reporting for specialty cancer care in Botswana, there is no association between HIV status and 1-year survival. [ABSTRACT FROM AUTHOR]

Purpose: Delays in diagnosis and treatment of cancers can lead to poor survival. These delays represent a multifaceted problem attributable to patient, provider, and systemic factors. We aim to quantify intervals from symptom onset to treatment start among patients with cancer in Botswana and to understand potential risk factors for delay. Patients and Methods: From December 2015 to January 2017, we surveyed patients seen in an oncology clinic in Botswana. We calculated proportions of patients who experienced delays in appraisal (between detecting symptoms and perceiving a reason to discuss them with provider, defined as > 1 month), help seeking (between discussing symptoms and first consultation with provider, defined as > 1 month), diagnosis (between first consultation and receiving a diagnosis, defined as > 3 months), and treatment (between diagnosis and starting treatment, defined as > 3 months). Results: Among 214 patients with cancer who completed the survey, median age at diagnosis was 46 years, and the most common cancer was cancer of the cervix (42.2%). Eighty-one percent of patients were women, 60.7% were HIV infected, and 56.6% presented with advanced cancer (stage III or IV). Twenty-six percent of patients experienced delays in appraisal, 35.5% experienced delays help seeking, 63.1% experienced delays in diagnosis, and 50.4% experienced delays in treatment. Patient income, education, and age were not associated with delays. In univariable analysis, patients living with larger families were less likely to experience a help-seeking delay (odds ratio [OR], 0.31; P =.03), women and patients with perceived very serious symptoms were less likely to experience an appraisal delay (OR, 0.45; P =.032 and OR, 0.14; P =.02, respectively). Conclusion: Nearly all patients surveyed experienced a delay in obtaining cancer care. In a setting where care is provided without charge, cancer type and male sex were more important predictors of delays than socioeconomic factors. [ABSTRACT FROM AUTHOR]

Purpose: In low- and middle-income countries (LMICs), frequent outages of the stock of cancer drugs undermine cancer care delivery and are potentially fatal for patients with cancer. The aim of this study is to describe a methodologic approach to forecast chemotherapy volume and estimate cost that can be readily updated and applied in most LMICs. Methods: Prerequisite data for forecasting are population-based incidence data and cost estimates per unit of drug to be ordered. We used the supplementary guidelines from the WHO list of essential medicines for cancer to predict treatment plans and ordering patterns. We used de-identified aggregate data from the Botswana National Cancer Registry to estimate incident cases. The WHO Management Sciences for Health International Price Indicator was used to estimate unit costs per drug. Results: Chemotherapy volume required for incident cancer cases was estimated as the product of the standardized dose required to complete a full treatment regimen per patient, with a given cancer diagnosis and stage, multiplied by the total number of incident cancer cases with the respective diagnosis. The estimated chemotherapy costs to treat the 10 most common cancers in the public health care sector of Botswana is approximately 2.3 million US dollars. An estimated 66% of the budget is allocated to costs of rituximab and trastuzumab alone, which are used by approximately 10% of the cancer population. Conclusion: This method provides a reproducible approach to forecast chemotherapy volume and cost in LMICs. The chemotherapy volume and cost outputs of this methodology provide key stakeholders with valuable information that can guide budget estimation, resource allocation, and drug-price negotiations for cancer treatment. Ultimately, this will minimize drug shortages or outages and reduce potential loss of lives that result from an erratic drug supply. [ABSTRACT FROM AUTHOR]

Purpose: Botswana has a high prevalence of HIV infection. Currently, there are few data regarding the sociodemographic factors, clinical characteristics, and outcomes of non-Hodgkin lymphoma (NHL)—an AIDS-defining cancer—in the country. Patients and Methods: This study used a prospective cancer registry to identify patients with a new diagnosis of NHL reporting for specialty cancer care at three hospitals in Botswana between October 2010 and August 2016. Treatment patterns and clinical outcomes were analyzed. Results: One hundred four patients with a new diagnosis of NHL were enrolled in this study, 72% of whom had HIV infection. Compared with patients not infected with HIV, patients infected with HIV were younger (median age, 53.9 v 39.1 years; P =.001) and more likely to present with an aggressive subtype of NHL (65.5% v 84.0%; P =.008). All patients infected with HIV received combined antiretroviral therapy throughout the course of the study, and similar chemotherapeutic regimens were recommended for all patients, regardless of subtype or HIV status (six to eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone; or cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab). There was no difference in 1-year mortality among patients not infected with HIV and patients infected with HIV (unadjusted analysis, 52.9% v 37.1%; hazard ratio [HR], 0.73; P =.33; adjusted analysis, HR, 0.57; P =.14). However, when compared with a cohort of patients in the United States matched by subtype, stage, age, sex, and race, patients in Botswana fared worse (1-year mortality, 22.8% v 46.3%; HR, 1.89; P =.001). Conclusion: Among patients with NHL reporting for specialty cancer care in Botswana, there is no association between HIV status and 1-year survival. [ABSTRACT FROM AUTHOR]

Purpose: Stock outs of cancer drugs are potentially fatal but have not been systematically studied in low- and middle-income countries. The aim of this study was to determine the availability and alignment of the Botswana National Essential Medicines List (NEML) for cancer drugs with the WHO's Essential Medicines List (EML). Methods: The availability and cost of cancer drugs were analyzed using data from a weekly stock catalog sent by Botswana's Central Medical Store to all pharmacy departments in government hospitals. Comparative data were extracted from the WHO EML and the "International Drug Price Indicator Guide-2014" from the Management Sciences for Health. Interviews with key informants were used to collect data on the Botswana NEML and the drug supply chain in the public sector. Results: The 2015 Botswana NEML for cancer had 80.5% alignment with the WHO EML. At least 40% of essential drugs were out of stock for a median duration of 30 days in 2015. Stock outs affected chemotherapy drugs included in first-line regimens for treating potentially curable diseases such as cervical, breast, and colorectal cancer and were not associated with buyer price of therapy. Analyses showed that the median price ratio for procured drugs was greater than 1 for 61% of the NEML drugs, which suggests inefficiency in procurement in the public sector. Conclusions: Botswana has one of the highest alignments of NEML to the WHO EML in the sub-Saharan African region, which is consistent with investment in the health care system evident in other clinical spheres. Better quantification of chemotherapy requirements using data from the National Cancer Registry and resource-sensitive treatment guidelines can help reduce stock outs and facilitate more effective and efficient procurement processes. [ABSTRACT FROM AUTHOR]

Background. Three-quarters of cancer deaths occur in resource-limited countries, and delayed presentation contributes to poor outcome. In Botswana, where more than half of cancers arise in HIV-infected individuals, we sought to explore predictors of timely oncology care and evaluate the hypothesis that engagement in longitudinal HIV care improves access. Methods. Consenting patients presenting for oncology care from October 2010 to September 2014 were interviewed and their records were reviewed. Cox and logistic models were used to examine the effect of HIV and other predictors on time to oncology care and presentation with advanced cancer (stage III or IV). Results. Of the 1,146 patients analyzed, 584 (51%) had HIV and 615 (54%) had advanced cancer. The initial clinic visit occurred a mean of 144 days (median 29, interquartile range 0-185) after symptom onset, but subsequent mean time to oncology care was 406 days (median 160, interquartile range 59-653). HIV status was not significantly associated with time to oncology care (adjusted hazard ratio [aHR] 0.91, 95% confidence interval [CI] 0.79-1.06). However, patients who reported using traditional medicine/healers engaged in oncology care significantly faster (aHR 1.23, 95% CI 1.09-1.40) and those with advanced cancer entered care earlier (aHR 1.48,95% CI 1.30-1.70). Factors significantly associated with advanced cancer included income,<$50 per month (adjusted odds ratio [aOR] 1.35, 95% CI 1.05-1.75), male sex (aOR 1.45, 95% CI 1.12-1.87), and pain as the presenting symptom (aOR 1.39, 95% CI 1.03-1.88). Conclusion. Longitudinal HIV care did not reduce the substantial delay to cancer treatment. Research focused on reducing health system delay through coordination and navigation is needed. [ABSTRACT FROM AUTHOR]

Background: The expansion of combination antiretroviral treatment (ART) in southern Africa has dramatically reduced mortality due to AIDS-related infections, but the impact of ART on cancer incidence in the region is unknown. We sought to describe trends in cancer incidence in Botswana during implementation of the first public ART program in Africa. Methods: We included 8479 incident cases from the Botswana National Cancer Registry during a period of significant ART expansion in Botswana, 2003–2008, when ART coverage increased from 7.3% to 82.3%. We fit Poisson models of age-adjusted cancer incidence and counts in the total population, and in an inverse probability weighted population with known HIV status, over time and estimated ART coverage. Findings: During this period 61.6% of cancers were diagnosed in HIV-infected individuals and 45.4% of all cancers in men and 36.4% of all cancers in women were attributable to HIV. Age-adjusted cancer incidence decreased in the HIV infected population by 8.3% per year (95% CI -14.1 to -2.1%). However, with a progressively larger and older HIV population the annual number of cancers diagnosed remained constant (0.0% annually, 95% CI -4.3 to +4.6%). In the overall population, incidence of Kaposi’s sarcoma decreased (4.6% annually, 95% CI -6.9 to -2.2), but incidence of non-Hodgkin lymphoma (+11.5% annually, 95% CI +6.3 to +17.0%) and HPV-associated cancers increased (+3.9% annually, 95% CI +1.4 to +6.5%). Age-adjusted cancer incidence among individuals without HIV increased 7.5% per year (95% CI +1.4 to +15.2%). Interpretation: Expansion of ART in Botswana was associated with decreased age-specific cancer risk. However, an expanding and aging population contributed to continued high numbers of incident cancers in the HIV population. Increased capacity for early detection and treatment of HIV-associated cancer needs to be a new priority for programs in Africa. [ABSTRACT FROM AUTHOR]

Background Despite population antiretroviral treatment (ART) utilization exceeding UNAIDS 90-90-90 targets, Kaposi sarcoma (KS) remains one of the most prevalent malignancies in Botswana. We sought to examine the characteristics and outcomes of KS in the context of high ART utilization. Methods Consenting patients at one of four oncology centers for KS treatment were enrolled prospectively (October 2010 to March 2019) and followed quarterly for 5 years. Survival was estimated using Kaplan–Meier estimator and predictors assessed with Cox proportional hazards modeling. Results A total of 408 KS patients were enrolled and of those, 396 (97%) were HIV-positive and included in analyses. Median age at diagnosis was 40 years (IQR: 34.1, 46.7) and 247 patients (62%) were male. The median CD4 cell count at the time of KS diagnosis was 253 cells/mL (IQR: 134, 364) and 279 (73%) were receiving ART at the time of KS diagnosis. Among those on ART, the median duration of ART prior to KS diagnosis was 11.9 months (IQR: 2.7, 46.7). The proportion receiving ART prior to KS increased during the surveillance period from 58% to 80% (P < 0.001). Of the 248 (62.6%) patients with recent measurement, 91% had HIV-1 RNA < 1000 copies/mL. Five-year overall survival was 73% (95% CI 68–78%). In multivariable analysis, Female sex and higher income were associated with improved survival, but not age or CD4 cell count. The duration of ART was significantly associated with survival (P = 0.02), with improved survival for individuals on ART < 6 months compared with longer ART (HR 0.54; 95% CI 0.29–0.98). The incidence of KS cases declined by nearly 50%, but has remained relatively stable since 2015. Conclusion Survival rates in this cohort were comparable to other KS cohorts. While KS treatment initially declined with ART expansion, KS remains a significant disease burden in Botswana with 80% of cases occurring among individuals receiving ART. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

The article reflects on the delivery of cancer care in Botswana which reveals the complexity of cancer. It highlights the medical drawbacks of Botswana including lack of oncologists, radiologists and pathologists, over-crowded and under-staffed hospitals, and confined public access to generic cytotoxic drugs. It states that efforts are made for oncology research after the successful programs for AIDS disease prevention and treatment.

Despite the rising burden of noncommunicable diseases, access to quality decentralized noncommunicable disease services remain limited in many low- and middle-income countries. Here we describe the strategies we employed to drive the process from adaptation to national endorsement and implementation of the 2016 Botswana primary healthcare guidelines for adults. The strategies included detailed multilevel assessment with broad stakeholder inputs and in-depth analysis of local data; leveraging academic partnerships; facilitating development of supporting policy instruments; and embedding noncommunicable disease guidelines within broader primary health-care guidelines in keeping with the health ministry strategic direction. At facility level, strategies included developing a multimethod training programme for health-care providers, leveraging on the experience of provision of human immunodeficiency virus care and engaging health-care implementers early in the process. Through the strategies employed, the country's first national primary health-care guidelines were endorsed in 2016 and a phased three-year implementation started in August 2017. In addition, provision of primary health-care delivery of noncommunicable disease services was included in the country's 11th national development plan (2017-2023). During the guideline development process, we learnt that strong interdisciplinary skills in communication, organization, coalition building and systems thinking, and technical grasp of best-practices in low- and middle-income countries were important. Furthermore, misaligned agendas of stakeholders, exaggerated by a siloed approach to guideline development, underestimation of the importance of having policy instruments in place and coordination of the processes initially being led outside the health ministry caused delays. Our experience is relevant to other countries interested in developing and implementing guidelines for evidence-based noncommunicable disease services. [ABSTRACT FROM AUTHOR]

Background: Adolescents and young adults account for more than one-third of incident Human Immunodeficiency Virus (HIV) infections globally. Understanding sexual practices of this high-risk group is critical in designing HIV targeted prevention programming. Objectives: To describe self-reported risky sexual practices of adolescents and young adults aged 16–24 years from 30 Botswana communities. Methods: Cross-sectional, self-reported age at sexual debut; number of sexual partners; condom and alcohol use during sex; intergenerational sex; and transactional sex data were collected. Modified Poisson estimating equations were used to obtain univariate and multivariate-adjusted prevalence ratios (PR) and 95% confidence intervals (CI) comparing engagement in different sexual practices according to gender, accounting for the clustered design of the study. Results: Among the 3380 participants, 2311 reported being sexually active with more females reporting being sexually active compared to males (65% vs. 35%, respectively; p < 0.0001). In univariate analyses, female participants were more likely to report inconsistent condom use (PR 1.61; 95% CI 1.44–1.80), intergenerational sex (PR 9.00; 95% CI 5.84–13.88) and transactional sex (PR 3.46; 95% CI 2.07–5.77) than males, yet less likely to report engaging in sex before age 15 years (PR 0.59; 95% CI: 0.41–0.85), using alcohol around the time of intercourse (PR: 0.59; 95% CI 0.45–0.76) or having ≥ two partners in the last 12 months (PR 0.65; 95% CI 0.57–0.74). Conclusions: Self-reported risky sexual practices of adolescents and young adults in Botswana differed significantly between males and females. Gender-specific risky sexual practices highlight the importance of developing tailored HIV prevention programming. [ABSTRACT FROM AUTHOR]

The article presents a study on the effect of highly active antiretroviral therapy (HAART) on the growth of HIV-uninfected infants in Botswana. It states that HIV-infected pregnant women from four sites in Botswana and HIV-uninfected infants were the subjects of the study. The study use the World Health Organization Child Growth Standards to calculate the growth of the infants. It concludes that the lower weights on HAART-exposed uninfected infants can be corrected in the first six months of life.

The article presents a study on the rates of HIV testing, CD4+ cell count testing, and highly active antiretroviral therapy (HAART) initiation during pregnancy among women giving birth at Princess Marina Hospital in Gaborone, Botswana. It reveals that 37% started HAART during their pregnancy, 42% received zidovudine prophylaxis, and 21% did not receive any therapy. It concludes that HAART initiation and CD4 cell count testing during pregnancy are low.

Purpose: People living with HIV (PLWH) experience increased risk of Hodgkin lymphoma (HL) despite effective initiation of antiretroviral therapy (ART). In high-income countries, outcomes following HIV HL have been reported to be non-differential, or inferior for PLWH. We sought to assess the effect of HIV on HL survival in Botswana, an African country with a generalized HIV epidemic and high ART coverage, to describe a context more reflective of global HIV populations., Patients and Methods: In the Thabatse Cancer Cohort, consenting participants initiating treatment for HL at one of four cancer centers in Botswana were enrolled from 2010 to 2020. Patients were followed quarterly for up to 5 years. The impact of HIV on survival following treatment initiation was assessed using an inverse probability-weighted Cox marginal structural model adjusted for age, performance status, and disease stage., Results: Seventy-eight new HL cases were enrolled, 47 (60%) were PLWH and 31 (40%) were HIV-uninfected. Baseline characteristics were similar between groups. The majority (61%) of patients presented with regional disease (stage I or II) with no statistically significant difference by HIV status ( P = .38). Nearly all (87%) PLWH participants were on ART before their HL diagnosis (median ART duration 42 months), and median CD4 count was 413 cells/μL (interquartile range 253-691). Survival, in unadjusted analyses, was lower among patients without HIV compared with PLWH (log rank P = .021). In adjusted analysis, HIV infection was not significantly associated with survival in inverse probability-weighted Cox model (hazard ratio 0.43; 95% CI, 0.16 to 1.16; P = .094)., Conclusion: In this cohort of patients treated for HL in Botswana, survival in PLWH (87% on long-standing ART) was at least as good as in individuals without HIV., Competing Interests: Aliyah SohaniConsulting or Advisory Role: AbbVie, MersanaExpert Testimony: Levin Papantonio Jason EfstathiouConsulting or Advisory Role: Blue Earth Diagnostics, AstraZeneca, Boston Scientific, Roivant, Merck, Myovant Sciences Philippe ArmandHonoraria: Merck, Bristol Myers SquibbConsulting or Advisory Role: Bristol Myers Squibb, Merck Sharp & Dohme, ADC Therapeutics, Celgene, Daiichi Sankyo, C4 Therapeutics, GenMab, Miltenyi Biotec, Enterome, Tessa Therapeutics, MorphoSys, Regeneron, Genentech/Roche, EpizymeResearch Funding: Merck Sharp & Dohme (Inst), Bristol Myers Squibb (Inst), Roche (Inst), Adaptive Biotechnologies (Inst), Affimed Therapeutics (Inst), Genentech (Inst), IGM (Inst), Kite, a Gilead Company (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, Merck Sharp & Dohme Scott Dryden-PetersonPatents, Royalties, Other Intellectual Property: Royalties received from UpToDate, Inc for article on HIVNo other potential conflicts of interest were reported.

Purpose: With intense HIV epidemics, southern African countries have a high burden of classic Hodgkin lymphoma (CHL) and non-Hodgkin lymphoma (NHL). However, suboptimal access to pathology resources limits subtype classification. We sought to assess the diagnostic accuracy of specimens classified as lymphoma and to determine association between discordant pathologic diagnosis and overall survival., Methods: Seventy patients with CHL or NHL and treated at three Botswana hospitals from 2010 to 2016 were analyzed. Local pathologic assessment relied primarily on morphology. All cases underwent secondary US hematopathology review, which is considered gold standard., Results: The median follow-up was 58 months. The overall reclassification rate was 20 of 70 cases (29%). All 20 CHL cases were correctly classified in Botswana, and mixed cellularity was the most common subtype, diagnosed in 11 (55%) cases. Of 47 confirmed NHL cases, diffuse large B-cell lymphoma was the final US diagnosis in 28 cases (60%), another aggressive B-cell NHL in nine (19%), an indolent B-cell NHL in six (13%), and T-cell NHL in four (9%). Common types of diagnostic discordance included NHL subtype reclassification (11 of 20, 55%) and CHL reclassified as NHL (7 of 20, 35%). Concordant versus discordant diagnosis after secondary review was associated with improved 5-year overall survival (60.1% v 26.3%, P = .0066). Discordant diagnosis was independently associated with increased risk of death (adjusted hazard ratio 2.733; 95% CI, 1.102 to 6.775; P = .0300) even after stratifying results by CHL versus NHL., Conclusion: In this single prospective cohort, discordant pathologic diagnosis was associated with a nearly three-fold increased risk of death. Limited access to relatively basic diagnostic techniques impairs treatment decisions and leads to poor patient outcomes in low-resource countries., Competing Interests: Jason A. EfstathiouConsulting or Advisory Role: Blue Earth Diagnostics, AstraZeneca, Boston Scientific, Roivant, Merck, Myovant Sciences Bruce A. ChabnerStock and Other Ownership Interests: Alnylam, Loxo, PharmaMar, Blueprint Medicines, GlaxoSmithKline, Biomarin, Seattle Genetics, SpringWorks Therapeutics, Constellation PharmaceuticalsHonoraria: Bristol Myers SquibbConsulting or Advisory Role: PharmaMar, EMD Serono, Cyteir, Chugai PharmaExpert Testimony: LillyTravel, Accommodations, Expenses: PharmaMar Jeremy AbramsonConsulting or Advisory Role: Celgene, Novartis, AbbVie, Kite, a Gilead company, Genentech, EMD Serono, MorphoSys, Alimera Sciences, Karyopharm Therapeutics, Bristol Myers Squibb, C4 Therapeutics¸ BeiGene, AstraZeneca, Incyte, Bluebird Bio, Kymera, Epizyme, Genmab, MorphoSys, MustangBio, Ono Pharmaceutical, RegeneronResearch Funding: Seattle Genetics (Inst), AI Therapeutics (Inst), Bristol Myers Squibb/Celgene (Inst) Scott L. Dryden-PetersonPatents, Royalties, Other Intellectual Property: Royalties received from UpToDate, Inc for article on HIV Aliyah R. SohaniConsulting or Advisory Role: AbbVie, MersanaExpert Testimony: Levin PapantonioNo other potential conflicts of interest were reported.

Purpose: We evaluated a clinical breast examination (CBE) screening program to determine the prevalence of breast abnormalities, number examined per cancer diagnosis, and clinical resources required for these diagnoses in a middle-income African setting., Methods: We performed a retrospective review of a CBE screening program (2015-2018) by Journey of Hope Botswana, a Botswana-based nongovernmental organization (NGO). Symptomatic and asymptomatic women were invited to attend. Screening events were held in communities throughout rural and periurban Botswana, with CBEs performed by volunteer nurses. Individuals who screened positive were referred to a private tertiary facility and were followed by the NGO. Data were obtained from NGO records., Results: Of 6,120 screened women (50 men excluded), 452 (7.4%) presented with a symptom and 357 (5.83%) were referred for further evaluation; 257 ultrasounds, 100 fine-needle aspirations (FNAs), 58 mammograms, and 31 biopsies were performed. In total, 6,031 were exonerated from cancer, 78 were lost to follow-up (67 for ≤ 50 years and 11 for > 50 years), and 11 were diagnosed with cancer (five for 41-50 years and six for > 50 years, 10 presented with symptoms). Overall breast cancer prevalence was calculated to be 18/10,000 (95% CI, 8 to 29/10,000). The number of women examined per breast cancer diagnosis was 237 (95% CI, 126 to 1910) for women of age 41-50 years and 196 (95% CI, 109 to 977) for women of age > 50 years. Median time to diagnosis for all women was 17.5 [1 to 32.5] days. CBE-detected tumors were not different than tumors presenting through standard care., Conclusion: In a previously unscreened population, yield from community-based CBE screening was high, particularly among symptomatic women, and required modest diagnostic resources. This strategy has potential to reduce breast cancer mortality.

Distance to care is a common exposure and proposed instrumental variable in health research, but it is vulnerable to violations of fundamental identifiability conditions for causal inference. We used data collected from the Botswana Birth Outcomes Surveillance study between 2014 and 2016 to outline 4 challenges and potential biases when using distance to care as an exposure and as a proposed instrument: selection bias, unmeasured confounding, lack of sufficiently well-defined interventions, and measurement error. We describe how these issues can arise, and we propose sensitivity analyses for estimating the degree of bias., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Stock outs of cancer drugs are potentially fatal but have not been systematically studied in low- and middle-income countries. The aim of this study was to determine the availability and alignment of the Botswana National Essential Medicines List (NEML) for cancer drugs with the WHO's Essential Medicines List (EML)., Methods: The availability and cost of cancer drugs were analyzed using data from a weekly stock catalog sent by Botswana's Central Medical Store to all pharmacy departments in government hospitals. Comparative data were extracted from the WHO EML and the "International Drug Price Indicator Guide-2014" from the Management Sciences for Health. Interviews with key informants were used to collect data on the Botswana NEML and the drug supply chain in the public sector., Results: The 2015 Botswana NEML for cancer had 80.5% alignment with the WHO EML. At least 40% of essential drugs were out of stock for a median duration of 30 days in 2015. Stock outs affected chemotherapy drugs included in first-line regimens for treating potentially curable diseases such as cervical, breast, and colorectal cancer and were not associated with buyer price of therapy. Analyses showed that the median price ratio for procured drugs was greater than 1 for 61% of the NEML drugs, which suggests inefficiency in procurement in the public sector., Conclusions: Botswana has one of the highest alignments of NEML to the WHO EML in the sub-Saharan African region, which is consistent with investment in the health care system evident in other clinical spheres. Better quantification of chemotherapy requirements using data from the National Cancer Registry and resource-sensitive treatment guidelines can help reduce stock outs and facilitate more effective and efficient procurement processes.

Background: HIV-1 RNA load is the best biological predictor of HIV transmission and treatment response. The rate of virologic suppression among key subpopulations can guide HIV prevention programs., Methods: The Botswana Combination Prevention Project performed a population-based household survey among adults in 30 communities in Botswana. Data collected included knowledge of HIV-positive status, antiretroviral therapy (ART) coverage, and virologic suppression (HIV-1 RNA ≤400 copies per milliliter). Individuals aged 16-29 years were considered young adults., Results: Among 552 young people living with HIV enrolled with RNA load data and ART status available, 51% (n = 279) had undetectable HIV-1 RNA, including 54% of young women and 32% of young men [sex prevalence ratio (PR): 0.53; 95% confidence interval (CI): 0.43 to 0.80; P < 0.001]. Compared with older adults (30-64 years old), young HIV-infected adults were significantly less likely to have undetectable HIV-1 RNA (PR: 0.65; 95% CI: 0.59 to 0.70; P < 0.0001), including both men (PR: 0.43; 95% CI: 0.34 to 0.56; P < 0.0001) and women (PR: 0.67; 95% CI: 0.62 to 0.74; P < 0.0001). Among a subset of people living with HIV receiving ART, young adults also were less likely to have undetectable HIV-1 RNA load than older adults (PR: 0.93; 95% CI: 0.90 to 0.95; P = <0.0001). Analysis of the care continuum revealed that inferior HIV diagnosis and suboptimal linkage to care are the primary reasons for low virologic suppression among young adults., Conclusions: Young adults in Botswana are significantly less likely to have undetectable HIV-1 RNA load compared with older adults. In the era of broad scale-up of ART, interventions able to diagnose young adults living with HIV and link them to effective therapy are urgently needed.

Purpose Delays in diagnosis and treatment of cancers can lead to poor survival. These delays represent a multifaceted problem attributable to patient, provider, and systemic factors. We aim to quantify intervals from symptom onset to treatment start among patients with cancer in Botswana and to understand potential risk factors for delay. Patients and Methods From December 2015 to January 2017, we surveyed patients seen in an oncology clinic in Botswana. We calculated proportions of patients who experienced delays in appraisal (between detecting symptoms and perceiving a reason to discuss them with provider, defined as > 1 month), help seeking (between discussing symptoms and first consultation with provider, defined as > 1 month), diagnosis (between first consultation and receiving a diagnosis, defined as > 3 months), and treatment (between diagnosis and starting treatment, defined as > 3 months). Results Among 214 patients with cancer who completed the survey, median age at diagnosis was 46 years, and the most common cancer was cancer of the cervix (42.2%). Eighty-one percent of patients were women, 60.7% were HIV infected, and 56.6% presented with advanced cancer (stage III or IV). Twenty-six percent of patients experienced delays in appraisal, 35.5% experienced delays help seeking, 63.1% experienced delays in diagnosis, and 50.4% experienced delays in treatment. Patient income, education, and age were not associated with delays. In univariable analysis, patients living with larger families were less likely to experience a help-seeking delay (odds ratio [OR], 0.31; P = .03), women and patients with perceived very serious symptoms were less likely to experience an appraisal delay (OR, 0.45; P = .032 and OR, 0.14; P = .02, respectively). Conclusion Nearly all patients surveyed experienced a delay in obtaining cancer care. In a setting where care is provided without charge, cancer type and male sex were more important predictors of delays than socioeconomic factors.

Background: Before introduction of tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV), 3-drug antiretroviral therapy (ART) was associated with increased adverse birth outcomes when used for prevention of mother-to-child HIV transmission (PMTCT) in Botswana., Methods: We extracted obstetric records from all women at the 2 largest maternities in Botswana from 2009-2011 when Botswana National Guidelines recommended zidovudine (ZDV) from 28 weeks gestational age (GA) for CD4 ≥350 and ART for CD4 <350, and again in 2013-2014 after implementation of TDF/FTC/EFV for prevention of mother-to-child HIV transmission regardless of CD4 or GA. We compared the use of TDF/FTC/EFV in pregnancy with other 3-drug ART regimens, and with initiation of ZDV, among women with similar CD4 cell counts. Outcomes included small for gestational age (SGA), preterm delivery (PTD) (<37 weeks GA), and stillbirths (SB)., Results: Among 9445 HIV-infected women delivering during the study period, 170 were on TDF/FTC/EFV at conception and 1468 initiated TDF/FTC/EFV during pregnancy. Adverse birth outcomes were high overall (3% SB, 21% PTD, and 18% SGA) and among women receiving TDF/FTC/EFV (3% SB, 22% PTD, and 12% SGA). There was no difference in PTD or SB among women initiating TDF/FTC/EFV compared with ZDV or other 3-drug ART, but initiating TDF/FTC/EFV was associated with fewer SGA infants than other 3-drug ART (adjusted odds ratio: 0.4, 95% confidence interval: 0.2 to 0.7)., Conclusions: Adverse birth outcomes remain high among HIV-infected women. TDF/FTC/EFV was at least as safe as other ART and associated with fewer SGA infants when initiated during pregnancy. Larger studies are needed to evaluate birth outcomes and congenital abnormalities among women on TDF/FTC/EFV at conception.

: Botswana was one of the first African countries to transition from WHO Option A to Option B for prevention of mother-to-child HIV transmission (MTCT). We evaluated the impact of this transition on projected MTCT risk through review of 10,681 obstetric records of HIV-infected women delivering at 6 maternity wards. Compared with Option A, women receiving antenatal care under Option B were more likely to receive combination antiretroviral therapy (ART), adjusted odds ratio (aOR): 2.59 (95% confidence interval: 2.25 to 2.98), but they were also more likely to receive no antenatal antiretrovirals, aOR: 2.10 (95% confidence interval: 1.74 to 2.53). Consequently, initial implementation of Option B was associated with increased projected MTCT at 6 months of age, 3.79% under Option A and 4.69% under Option B (P < 0.001). Successful implementation of Option B or B+ may require that ART can be initiated within antenatal clinics, and novel strategies to remove barriers to rapid ART initiation.

Few studies have compared the programmatic effectiveness of the recommended strategies of antenatal highly active antiretroviral therapy (HAART) and zidovudine for prevention of mother-to-child transmission. We prospectively followed infants (93% formula fed) whose mothers who took either HAART (258 infants) or zidovudine (170 infants) during pregnancy in the Botswana national program. Overall, 10 infants (2.5%) acquired HIV--9 infants in the zidovudine group (5.5%, 95% confidence interval: 2.6% to 10.2%) and 1 infant in the HAART group (0.4%, 95% confidence interval: 0.0% to 2.2%). Maternal HAART was associated with decreased prevention of mother-to-child transmission (P = 0.001) and improved HIV-free survival (P = 0.040) compared with zidovudine (with or without single-dose nevirapine) in a programmatic setting.

Background: Maternal highly-active antiretroviral therapy (HAART) reduces mother-to-child HIV transmission but may increase the risk for infant anemia., Methods: The incidence of first severe anemia (grade 3 or 4, Division of AIDS 2004 Toxicity Table) was assessed among HIV-uninfected infants in the Mashi and Mma Bana mother-to-child HIV transmission prevention trials in Botswana. Severe anemia rates were compared between 3 groups: infants exposed to maternal HAART in utero and during breastfeeding (BF) and 1 month of postnatal zidovudine (ZDV) (HAART-BF); infants exposed to maternal ZDV in utero, 6 months of postnatal ZDV, and BF (ZDV-BF); and infants exposed to maternal ZDV in utero, 1 month of postnatal ZDV, and formula-feeding (ZDV-FF)., Results: A total of 1719 infants were analyzed-691 HAART-BF, 503 ZDV-BF, and 525 ZDV-FF. Severe anemia was detected in 118 infants (7.4%). By 6 months, 12.5% of HAART-BF infants experienced severe anemia, compared with 5.3% of ZDV-BF (P < 0.001) and 2.5% of ZDV-FF infants (P < 0.001). In adjusted analysis, HAART-BF infants were at greater risk of severe anemia than ZDV-BF or ZDV-FF infants (adjusted odds ratios 2.6 and 5.8, respectively; P < 0.001). Most anemias were asymptomatic and improved with iron/multivitamin supplementation and cessation of ZDV exposure. However, 11 infants (0.6% of all infants) required transfusion for symptomatic anemia. Microcytosis and hypochromia were common among infants with severe anemia., Conclusions: Exposure to maternal HAART starting in utero was associated with severe infant anemia. Confirmation of this finding and possible strategies to mitigate hematologic toxicity warrant further study.

Background: Botswana has the most comprehensive public program in Africa for providing antiretroviral therapy to treat HIV and prevent mother-to-child transmission (PMTCT). Botswana guidelines prioritize CD4(+) cell count testing during pregnancy and initiation of highly active antiretroviral treatment (HAART) for women who qualify for treatment. We analyzed rates of HIV testing, CD4 cell count testing, and HAART initiation during pregnancy., Methods: From October 2007 through June 2008, we reviewed obstetric and laboratory records of women at Princess Marina Hospital in Gaborone, Botswana., Results: We recorded information from 3056 women. Of 2675 women eligible for the PMTCT program, 2623 (98%) had a documented HIV status, of whom 793 (30%) were HIV infected. Among women who were treatment naive at pregnancy conception, 397 (59%) had recorded CD4(+) cell counts, of whom 62 (16%) had a CD4(+) cell count <200 cells per cubic millimeter. Among this subset, 23 (37%) initiated HAART during pregnancy, 26 (42%) received zidovudine prophylaxis, and 13 (21%) received no therapy., Conclusions: We observed low rates of CD4(+) cell count testing and HAART initiation during pregnancy. Antenatal clinics should prioritize CD4(+) cell count testing and referral of women who qualify for HAART to maximize benefits of maternal treatment and PMTCT.