Aggrey Semeere

Impact of antiretroviral therapy on the incidence of Kaposi's sarcoma in resource-rich and resource-limited settings.

Purpose of review Given the recent availability of antiretroviral therapy (ART) in resource-limited settings and the significant burden exacted by Kaposis sarcoma in these areas, we reviewed data regarding the impact of ART on Kaposis sarcoma incidence. We summarized the sizeable literature in resource-rich settings as well as emerging data from resource-limited regions. Importantly, we delineated ways impact can be defined, including individual patient-level effectiveness; population-level effectiveness; change in population-level incidence; and residual risk of Kaposis sarcoma. Recent findings In resource-rich settings, there are now ample data demonstrating beneficial individual patient-level and population-level effects of ART on Kaposis sarcoma incidence. There is, however, considerable variability between studies and important methodologic shortcomings. Data from resource-limited settings are much more limited; although they preliminarily indicate individual patient-level effectiveness, they do not yet provide insight on population-level effects. Summary ART has had a substantial impact on Kaposis sarcoma incidence in resource-rich settings, but more attention is needed on validly quantifying this effect in order to determine whether additional interventions are needed. Emerging data from resource-limited regions also suggest beneficial impact of ART on Kaposis sarcoma incidence, but – given the scope of Kaposis sarcoma in these settings – more data are needed to understand the breadth and magnitude of the effect.

A prospective ascertainment of cancer incidence in sub-Saharan Africa: The case of Kaposi sarcoma.

In resource‐limited areas, such as sub‐Saharan Africa, problems in accurate cancer case ascertainment and enumeration of the at‐risk population make it difficult to estimate cancer incidence. We took advantage of a large well‐enumerated healthcare system to estimate the incidence of Kaposi sarcoma (KS), a cancer which has become prominent in the HIV era and whose incidence may be changing with the rollout of antiretroviral therapy (ART). To achieve this, we evaluated HIV‐infected adults receiving care between 2007 and 2012 at any of three medical centers in Kenya and Uganda that participate in the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium. Through IeDEA, clinicians received training in KS recognition and biopsy equipment. We found that the overall prevalence of KS among 102,945 HIV‐infected adults upon clinic enrollment was 1.4%; it declined over time at the largest site. Among 140,552 patients followed for 319,632 person‐years, the age‐standardized incidence rate was 334/100,000 person‐years (95% CI: 314–354/100,000 person‐years). Incidence decreased over time and was lower in women, persons on ART, and those with higher CD4 counts. The incidence rate among patients on ART with a CD4 count >350 cells/mm3 was 32/100,000 person‐years (95% CI: 14–70/100,000 person‐years). Despite reductions over time coincident with the expansion of ART, KS incidence among HIV‐infected adults in East Africa equals or exceeds the most common cancers in resource‐replete settings. In resource‐limited settings, strategic efforts to improve cancer diagnosis in combination with already well‐enumerated at‐risk denominators can make healthcare systems attractive platforms for estimating cancer incidence.

Mortality and immunological recovery among older adults on antiretroviral therapy at a large urban HIV clinic in Kampala, Uganda

Background:We describe older (>50 years) HIV-infected adults after antiretroviral therapy (ART) initiation, evaluating immunological recovery by age category, considering individual trajectories based on the pretreatment CD4. We also describe mortality on ART and its risk factors by age category including the contribution of poor immunological recovery at a large urban clinic in Kampala, Uganda. Methods:We performed a cohort analysis of adult (>18 years) HIV-infected patients who initiated ART between January 1, 2004 and January 3, 2012. Immunological response was evaluated using mixed-effects linear regression. We described mortality using Kaplan–Meier survival methods analyzing for risk factors of mortality using multivariate Weibull survival regression stratified by age category. Results:Among 9806 individuals who initiated ART, mean age was 37 years (SD: 8.8), average follow-up 5.7 years (SD: 1.7), and median baseline CD4 was 115 cells per cubic millimeter (interquartile range: 42–184). Adults younger than 50 years had on average a higher CD4 increase of 45 cells per cubic millimeter (95% confidence interval: 17 to 72; P = 0.001) compared with counterparts aged 60 years and older. Mortality was highest among older adults compared with younger counterparts. Only CD4 count <100 cells per cubic millimeter after 1 year on ART and a CD4 count less than baseline were associated with a statistically significant higher rate of death among older adults. Conclusions:Older adults had a slower immunological response, which was associated with mortality, but this mortality was not typically associated with opportunistic infections. Future steps would require more evaluation of possible causes of death among these older individuals if survival on ART is to be further improved.

Task Shifting and Skin Punch for the Histologic Diagnosis of Kaposi's Sarcoma in Sub-Saharan Africa: A Public Health Solution to a Public Health Problem

Fueled by HIV, sub-Saharan Africa has the highest incidence of Kaposis sarcoma (KS) in the world. Despite this, KS diagnosis in the region is based mostly on clinical grounds. Where biopsy is available, it has traditionally been excisional and performed by surgeons, resulting in multiple appointments, follow-up visits for suture removal, and substantial costs. We hypothesized that a simpler approach - skin punch biopsy - would make histologic diagnosis more accessible. To address this, we provided training and equipment for skin punch biopsy of suspected KS to three HIV clinics in East Africa. The procedure consisted of local anesthesia followed by a disposable cylindrical punch blade to obtain specimens. Hemostasis is facilitated by Gelfoam®. Patients removed the dressing after 4 days. From 2007 to 2013, 2,799 biopsies were performed. Although originally targeted to be used by physicians, biopsies were performed predominantly by nurses (62%), followed by physicians (15%), clinical officers (12%) and technicians (11%). There were no reports of recurrent bleeding or infection. After minimal training and provision of inexpensive equipment (USD 3.06 per biopsy), HIV clinics in East Africa can integrate same-day skin punch biopsy for suspected KS. Task shifting from physician to non-physician greatly increases access. Skin punch biopsy should be part of any HIV clinics essential procedures. This example of task shifting may also be applicable to the diagnosis of other cancers (e.g., breast) in resource-limited settings.

Innovative Demand Creation for Voluntary Medical Male Circumcision Targeting a High Impact Male Population: A Pilot Study Engaging Pregnant Women at Antenatal Clinics in Kampala, Uganda

Background:Circumcision has been shown to be an effective method of HIV prevention; however, only 28% of Ugandan men aged 15–49 years are circumcised. There is a paucity of data on the role of intimate partners in generating demand for voluntary medical male circumcision (VMMC). We conducted a pilot study to assess the feasibility of a partner-focused intervention targeting males >25 years. Methods:Among pregnant women in their third trimester attending antenatal care we evaluated the impact of a pilot behavior change intervention on VMMC through a quasi-experimental approach. We observed VMMC numbers among spouses of women as per standard practice (comparison phase), and after introducing a behavioral change communication package (intervention phase). Logistic regression was used to compare the odds of VMMC uptake between comparison and intervention phases. We used qualitative methods to evaluate the casual chain using a thematic approach. Results:Of the 601 women studied, 90% articulated the health benefits of VMMC and 99% expressed interest in their spouse getting circumcised. Womens knowledge was not increased by the intervention. Four men were circumcised in the comparison and 7 in the intervention phase. The intervention was not associated with higher odds of circumcision (odds ratio 1.5, 95% CI: 0.3 to 6.0, P = 0.65). We interviewed 117 individuals overall with the main enablers for VMMC being: free VMMC, transport reimbursement, and health benefits. Deterrents included misconceptions, lost wages and fear of pain. Most of the uncircumcised men interviewed reported interest in VMMC. Conclusions:Our pilot intervention had no significant impact on increasing VMMC demand. The study demonstrated the feasibility of pregnant women engaging their spouses to discuss VMMC.

Hypertension and associated risk factors in individuals infected with HIV on antiretroviral therapy at an urban HIV clinic in Uganda

Abstract Background Scale-up of antiretroviral therapy (ART) might precipitate an increase in non-communicable diseases (NCDs) in adults infected with HIV in sub-Saharan Africa based on data from resource-rich settings. Hypertension is a major modifiable risk factor for cerebrovascular and cardiovascular NCDs. We estimated prevalence, incidence, and risk factors for incident hypertension in adults infected with HIV on ART at an urban clinic in Uganda. Methods From a cohort of adults infected with HIV (>18 years) who initiated ART between Jan 1, 2005, and Jan 3, 2012, at the Infectious Diseases Institute clinic in Kampala, we report the prevalence, incidence, and cumulative incidence (with death as a competing risk) of hypertension (≥140/90 mm Hg). Risk factors for hypertension were evaluated with Cox proportional hazards regression. Findings Of 9806 individuals who initiated ART, 6351 (64·8%) were women, median age was 36 years (IQR 31–42), and median follow-up was 3·9 years (2·2–5·9). Overall prevalence of hypertension was 15·1% (1472 individuals); older individuals (>50 years) had higher prevalence (299, 38·6%). By year 1, cumulative incidence was 1% and by year 5, it was 3·6%. Overall incidence was 19 cases per 1000 person-years. Multivariate regression showed male sex, older age, increasing body-mass index, and use of stavudine at initiation was associated with an increased rate of hypertension. Interpretation Of our patients, we noted a prevalence of hypertension between 14·6% and 28·5%, similar to the general Ugandan population. Besides traditional risk factors for hypertension, use of stavudine was also identified. Awareness of NCD comorbidity and AIDS-associated risk factors are increasingly important for clinicians caring for adults on ART in sub-Saharan Africa. Funding University of California Global Health Institute (UCGHI) supported GloCal Fellowship funded by the Fogarty International Center (FIC) at the National Institutes of Health (NIH) R25TW009343 .

A portable device for nucleic acid quantification powered by sunlight, a flame or electricity

A decentralized approach to diagnostics can decrease the time to treatment of infectious diseases in resource-limited settings, yet most modern diagnostic tools require stable electricity and are not portable. Here, we describe a portable device for isothermal nucleic acid quantification that can operate with power from electricity, sunlight or a flame, and that can store heat from intermittent energy sources for operation when electrical power is not available or reliable. We deployed the device in two Ugandan health clinics, where it successfully operated through multiple power outages, with equivalent performance when powered via sunlight or electricity. A direct comparison between the portable device and commercial quantitative polymerase chain reaction machines for samples from 71 Ugandan patients (29 of which were tested in Uganda) for the presence of Kaposi’s sarcoma-associated herpesvirus DNA showed 94% agreement, with the four discordant samples having the lowest concentration of the herpesvirus DNA. The device’s flexibility in power supply provides a needed solution for on-field diagnostics.A point-of-care device that can run on a variety of power inputs enables isothermal nucleic acid quantification for the diagnosis of infectious diseases in resource-limited settings with unreliable electrical power supply.