Person:

Dryden-Peterson, Scott

Background: Prophylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia. Methods: We compared the proportion of HIV-exposed uninfected (HIV-EU) infants experiencing incident severe anemia (and separately, severe neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole from 1 to 6 months vs. infants from two prior trials who did not receive cotrimoxazole. Infants were from rural and urban communities in southern Botswana. Results: A total of 1705 HIV-EU infants were included. Among these 645 (37.8%) were fed with iron-supplemented formula from birth. Severe anemia developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In an analysis stratified by infant feeding method, there were no significant differences in the risk of severe anemia by prophylactic cotrimoxazole exposure–risk difference, −0.69% (95% confidence interval [CI] −2.1 to 0.76%). Findings were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI 0.07 to 1.65). There were also no significant differences observed for severe neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI −1.3 to 5.2%) and aOR 0.80 (95% CI 0.33 to 1.93). Conclusions: Severe anemia and severe neutropenia were infrequent among HIV-exposed uninfected infants receiving cotrimoxazole from 1–6 months of age. Concerns regarding hematologic toxicity should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected infants. ClinicalTrials.gov Registration Numbers NCT01086878 (http://clinicaltrials.gov/show/NCT01086878), NCT00197587 (http://clinicaltrials.gov/show/NCT00197587), and NCT00270296 (http://clinicaltrials.gov/show/NCT00270296).

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.

Background: Less than one-third of HIV-infected pregnant women eligible for combination antiretroviral therapy (ART) globally initiate treatment prior to delivery, with lack of access to timely CD4 results being a principal barrier. We evaluated the effectiveness of an SMS-based intervention to improve access to timely antenatal ART. Methods: We conducted a stepped-wedge cluster randomized trial of a low-cost programmatic intervention in 20 antenatal clinics in Gaborone, Botswana. From July 2011-April 2012, 2 clinics were randomly selected every 4 weeks to receive an ongoing clinic-based educational intervention to improve CD4 collection and to receive CD4 results via an automated SMS platform with active patient tracing. CD4 testing before 26 weeks gestation and ART initiation before 30 weeks gestation were assessed. Results: Three-hundred-sixty-six ART-naïve women were included, 189 registering for antenatal care under Intervention and 177 under Usual Care periods. Of CD4-eligible women, 100 (59.2%) women under Intervention and 79 (50.6%) women under Usual Care completed CD4 phlebotomy before 26 weeks gestation, adjusted odds ratio (aOR, adjusted for time that a clinic initiated Intervention) 0.87 (95% confidence interval [CI]0.47–1.63, P = 0.67). The SMS-based platform reduced time to clinic receipt of CD4 test result from median of 16 to 6 days (P<0.001), was appreciated by clinic staff, and was associated with reduced operational cost. However, rates of ART initiation remained low, with 56 (36.4%) women registering under Intervention versus 37 (24.2%) women under Usual Care initiating ART prior to 30 weeks gestation, aOR 1.06 (95%CI 0.53–2.13, P = 0.87). Conclusions: The augmented SMS-based intervention delivered CD4 results more rapidly and efficiently, and this type of SMS-based results delivery platform may be useful for a variety of tests and settings. However, the intervention did not appear to improve access to timely antenatal CD4 testing or ART initiation, as obstacles other than CD4 impeded ART initiation during pregnancy.

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. Implications for Practice: The majority (54%) of patients in this large cohort from Botswana presented with advanced-stage cancer despite universal access to free health care. Median time from first symptom to specialized oncology care was 13 months. For HIV-infected patients (51% of total), regular longitudinal contact with the health system, through quarterly doctor visits for HIV management, was not successful in providing faster linkages into oncology care. However, patients who used traditional medicine/healers engaged in cancer care faster, indicating potential for leveraging traditional healers as partners in early cancer detection. New strategies are urgently needed to facilitate diagnosis and timely treatment of cancer in low- and middle-income countries.

Introduction: Health system delays in diagnosis of cancer contribute to the glaring disparities in cancer mortality between high-income countries and low- and middle-income countries. In Botswana, approximately 70% of cancers are diagnosed at late stage and median time from first health facility visit for cancer-related symptoms to specialty cancer care was 160 days (IQR 59–653). We describe the implementation and early outcomes of training targeting primary care providers, which is a part of a multi-component implementation study in Kweneng-East district aiming to enhance timely diagnosis of cancers. Methods: Health-care providers from all public facilities within the district were invited to participate in an 8-h intensive short-course program developed by a multidisciplinary team and adapted to the Botswana health system context. Participants’ performance was assessed using a 25-multiple choice question tool, with pre- and post-assessments paired by anonymous identifier. Statistical analysis with Wilcoxon signed-rank test to compare performance at the two time points across eight sub-domains (pathophysiology, epidemiology, social context, symptoms, evaluation, treatment, documentation, follow-up). Linear regression and negative binomial modeling were used to determine change in performance. Participants’ satisfaction with the program was measured on a separate survey using a 5-point Likert scale. Results: 176 participants attended the training over 5 days in April 2016. Pooled linear regression controlling for test version showed an overall performance increase of 16.8% after participation (95% CI 15.2–18.4). Statistically significant improvement was observed for seven out of eight subdomains on test A and all eight subdomains on test B. Overall, 71 (40.3%) trainees achieved a score greater than 70% on the pretest, and 161 (91.5%) did so on the posttest. Participants reported a high degree of satisfaction with the training program’s content and its relevance to their daily work. Conclusion: We describe a successfully implemented primary health care provider-focused training component of an innovative intervention aiming to reduce health systems delays in cancer diagnosis in sub-Saharan Africa. The training achieved district-wide participation, and improvement in the knowledge of primary health-care providers in this setting. Clinical Trial Registration www.ClinicalTrials.gov, identifier NCT02752061.