All-cause and cause-specific mortality rates for Kisumu County: a comparison with Kenya, low-and middle-income countries.

BACKGROUND: Understanding the magnitude and causes of mortality at national and sub-national levels for countries is critical in facilitating evidence-based prioritization of public health response. We provide comparable cause of death data from Kisumu County, a high HIV and malaria-endemic county in Kenya, and compared them with Kenya and low-and-middle income countries (LMICs). METHODS: We analyzed data from a mortuary-based study at two of the largest hospital mortuaries in Kisumu. Mortality data through 2019 for Kenya and all LMICs were downloaded from the Global Health Data Exchange. We provided age-standardized rates for comparisons of all-cause and cause-specific mortality rates, and distribution of deaths by demographics and Global Burden of Disease (GBD) classifications. RESULTS: The all-cause age-standardized mortality rate (SMR) was significantly higher in Kisumu compared to Kenya and LMICs (1118 vs. 659 vs. 547 per 100,000 population, respectively). Among women, the all-cause SMR in Kisumu was almost twice that of Kenya and double the LMICs rate (1150 vs. 606 vs. 518 per 100,000 population respectively). Among men, the all-cause SMR in Kisumu was approximately one and a half times higher than in Kenya and nearly double that of LMICs (1089 vs. 713 vs. 574 per 100,000 population). In Kisumu and LMICs non-communicable diseases accounted for most (48.0 and 58.1% respectively) deaths, while in Kenya infectious diseases accounted for the majority (49.9%) of deaths. From age 10, mortality rates increased with age across all geographies. The age-specific mortality rate among those under 1 in Kisumu was nearly twice that of Kenya and LMICs (6058 vs. 3157 and 3485 per 100,000 population, respectively). Mortality from injuries among men was at least one and half times that of women in all geographies. CONCLUSION: There is a notable difference in the patterns of mortality rates across the three geographical areas. The double burden of mortality from GBD Group I and Group II diseases with high infant mortality in Kisumu can guide prioritization of public health interventions in the county. This study demonstrates the importance of establishing reliable vital registry systems at sub-national levels as the mortality dynamics and trends are not homogeneous.

Mortuary and hospital-based HIV mortality surveillance among decedents in a low-resource setting: lessons from Western Kenya.

BACKGROUND: Lack of dependable morbidity and mortality data complicates efforts to measure the demographic or population-level impact of the global HIV/AIDS epidemic. Mortuary-based mortality surveillance can address gaps in vital statistics in low-resource settings by improving accuracy of measuring HIV-associated mortality and indicators of access to treatment services among decedents. This paper describes the process and considerations taken in conducting mortuary and hospital-based HIV mortality surveillance among decedents in Kenya. MAIN TEXT: We conducted HIV mortuary and hospital-based mortality surveillance at two of the largest mortuaries in Kisumu County, Kenya (April 16-July 12, 2019). Medical charts were reviewed for documentation of HIV status among eligible decedents. HIV testing was done on blood and oral fluid samples from decedents with undocumented HIV status and those whose medical records indicated HIV-negative test results > 3 months before death. A panel of experts established the cause of death according to the International Classification of Diseases, 10th Revision rules. Civil registry data for the year 2017 were abstracted and coded to corresponding ICD-10 codes. Of the 1004 decedents admitted to the two mortuaries during the study period, 49 (4.9%) were unavailable because they had been transferred to other facilities or dispatched for burial before enrolment. Of the 955 available decedents, 104 (10.9%) were ineligible for the study. Blood samples were collected from 659 (77.4%) decedents, and 654 (99.2%) were tested for HIV. Of the 564 decedents eligible for the OraQuick® validation sub-study, 154 were eligible for oral sample collection, and 132 (85.7%) matched pre- and post-embalming oral samples were collected and tested. Of the 851 eligible decedents, 241 (28.3%) had evidence of HIV infection: 119 had a diagnosis of HIV infection recorded in their patient files, and 122 had serological evidence of HIV infection. CONCLUSION: This study shows that in low-resource settings, conducting hospital and mortuary-based surveillance is feasible and can be an alternative source of mortality data when civil registry data are inadequate.

Evaluation of the Performance of OraQuick Rapid HIV-1/2 Test Among Decedents in Kisumu, Kenya.

BACKGROUND: Estimating cause-related mortality among the dead is not common, yet for clinical and public health purposes, a lot can be learnt from the dead. HIV/AIDS accounted for the third most frequent cause of deaths in Kenya; 39.7 deaths per 100,000 population in 2019. OraQuick Rapid HIV-1/2 has previously been validated on oral fluid and implemented as a screening assay for HIV self-testing in Kenya among living subjects. We assessed the feasibility and diagnostic accuracy of OraQuick Rapid HIV-1/2 for HIV screening among decedents. METHODS: Trained morticians collected oral fluid from 132 preembalmed and postembalmed decedents aged >18 months at Jaramogi Oginga Odinga Teaching and Referral Hospital mortuary in western Kenya and tested for HIV using OraQuick Rapid HIV-1/2. Test results were compared with those obtained using the national HIV Testing Services algorithm on matched preembalming whole blood specimens as a gold standard (Determine HIV and First Response HIV 1-2-O). We calculated positive predictive values, negative predictive values, area under the curve, and sensitivity and specificity of OraQuick Rapid HIV-1/2 compared with the national HTS algorithm. RESULTS: OraQuick Rapid HIV-1/2 had similar sensitivity of 92.6% [95% confidence interval (CI): 75.7 to 99.1] on preembalmed and postembalmed samples compared with the gold standard. Specificity was 97.1% (95% CI: 91.9 to 99.4) and 95.2% (95% CI: 89.2 to 98.4) preembalming and postembalming, respectively. Preembalming and postembalming positive predictive value was 89.3% (95% CI: 71.8 to 97.7) and 83.3% (95% CI: 65.3 to 94.4), respectively. The area under the curve preembalming and postembalming was 94.9% (95% CI: 89.6 to 100) and 93.9% (95% CI: 88.5 to 99.4), respectively. CONCLUSIONS: The study showed a relatively high-performance sensitivity and specificity of OraQuick Rapid HIV-1/2 test among decedents, similar to those observed among living subjects. OraQuick Rapid HIV-1/2 presents a convenient and less invasive screening test for surveillance of HIV among decedents within a mortuary setting.

High HIV prevalence among decedents received by two high-volume mortuaries in Kisumu, western Kenya, 2019.

BACKGROUND: Accurate data on HIV-related mortality are necessary to evaluate the impact of HIV interventions. In low- and middle-income countries (LMIC), mortality data obtained through civil registration are often of poor quality. Though not commonly conducted, mortuary surveillance is a potential complementary source of data on HIV-associated mortality. METHODS: During April-July 2019, we assessed HIV prevalence, the attributable fraction among the exposed, and the population attributable fraction among decedents received by two high-volume mortuaries in Kisumu County, Kenya, where HIV prevalence in the adult population was estimated at 18% in 2019 with high ART coverage (76%). Stillbirths were excluded. The two mortuaries receive 70% of deaths notified to the Kisumu East civil death registry; this registry captures 45% of deaths notified in Kisumu County. We conducted hospital chart reviews to determine the HIV status of decedents. Decedents without documented HIV status, including those dead on arrival, were tested using HIV antibody tests or polymerase chain reaction (PCR) consistent with national HIV testing guidelines. Decedents aged less than 15 years were defined as children. We estimated annual county deaths by applying weights that incorporated the study period, coverage of deaths, and mortality rates observed in the study. RESULTS: The two mortuaries received a total of 1,004 decedents during the study period, of which 95.1% (955/1004) were available for study; 89.1% (851/955) of available decedents were enrolled of whom 99.4% (846/851) had their HIV status available from medical records and post-mortem testing. The overall population-based, age- and sex-adjusted mortality rate was 12.4 per 1,000 population. The unadjusted HIV prevalence among decedents was 28.5% (95% confidence interval (CI): 25.5-31.6). The age- and sex-adjusted mortality rate in the HIV-infected population (40.7/1000 population) was four times higher than in the HIV-uninfected population (10.2/1000 population). Overall, the attributable fraction among the HIV-exposed was 0.71 (95% CI: 0.66-0.76) while the HIV population attributable fraction was 0.17 (95% CI: 0.14-0.20). In children the attributable fraction among the exposed and population attributable fraction were 0.92 (95% CI: 0.89-0.94) and 0.11 (95% CI: 0.08-0.15), respectively. CONCLUSIONS: Over one quarter (28.5%) of decedents received by high-volume mortuaries in western Kenya were HIV-positive; overall, HIV was considered the cause of death in 17% of the population (19% of adults and 11% of children). Despite substantial scale-up of HIV services, HIV disease remains a leading cause of death in western Kenya. Despite progress, increased efforts remain necessary to prevent and treat HIV infection and disease.

Prevalence of self-reported symptoms of sexually transmitted infections, knowledge and sexual behaviour among youth in semi-rural Tanzania in the period of adolescent friendly health services strategy implementation.

BACKGROUND: Global evidence shows that sexually transmitted infections (STIs) prevalence and sexual risk behaviours are high among youth, and knowledge about STIs is low. In Tanzania, there is limited recent evidence regarding these issues. The aim of this study was to describe the health seeking behaviour of youth reporting STI symptoms in semi-rural Tanzania and to evaluate the association of socio-demographic characteristics, STI knowledge and sexual risk behaviour with STI symptom reporting. METHODS: This was a cross-sectional study involving 2251 sexually experienced youth (15-24 years), who participated in a larger baseline survey of a cohort within Ifakara town. Interview data were electronically collected by trained field workers. Logistic regression analysis was used to identify factors that influence the risk of reporting STI symptoms within the past year, using Stata 12.1. RESULTS: The prevalence of self-reported STI symptoms in the past year was 19.9%. Almost all of youth had heard of STIs and 32.7% of youth could mention at least one sign. 34.4% had sought care for their STI symptoms, the majority at private facilities. Only 20% of HIV-STI co-infected youth was aware of their HIV status. Youth with more knowledge of STI symptoms reported to have had symptoms more often (OR = 1.28; 95% CI 1.01-1.62), and those reporting having first sex at 16 or under were more likely to report STI symptoms than those who delayed to 17-19 years (OR 1.27; 95% CI 1.003-1.62). CONCLUSION: These findings highlight the need to improve the implementation of Adolescent Friendly Health Services available in Tanzania (especially in semi-rural areas). The inclusion of private facilities and pharmacies in AFHS scale-up would potentially raise the level of STI knowledge, lower the STI prevalence and reduce HIV incidence among youth.

Socio-demographic inequalities in HIV testing behaviour and HIV prevalence among older adults in rural Tanzania, 2013.

Most HIV research in Sub-Saharan Africa (SSA) ignores persons aged 50 years and above, though a few studies have reported a high HIV prevalence among older people. This study aimed to estimate socio-demographic inequalities in HIV testing behaviour and HIV prevalence among adults aged 50+ years, living in Ifakara town, Tanzania. This cross-sectional study used data from the baseline measurement of the Ifakara MZIMA cohort study in 2012/13. Consenting participants were interviewed and tested for HIV. Associations between HIV testing behaviour and HIV prevalence with socio-demographic indicators were explored with multivariable logistic regression. Among the 1643 adults 50+ years included in the study, HIV prevalence and the HIV testing rate (ever tested) were 6% and 11.4% respectively. The HIV testing rate was lower for older people (aOR = 0.19 (95% CI 0.09-0.41 for 75+ versus 50-54 years); higher for those separated/divorced/widowed than those married (aOR = 1.46; 1.02-2.10); higher for "other Christians" than Muslims (aOR = 1.95; 1.06-3.58); and higher for primary (aOR = 1.54; 1.01-2.33) and secondary (aOR = 3.47; 2.11-5.70) school graduates than those without education. HIV prevalence was lower for older people (aOR = 0.27; 0.11-0.66 for 75+ versus 50-54); and for Catholics compared to Muslims (aOR = 0.54; 0.34-0.85). The high HIV prevalence among older adults and the low HIV testing behaviour call for more efforts on HIV prevention, treatment and care.

A qualitative study of the determinants of HIV guidelines implementation in two south-eastern districts of Tanzania.

Current HIV policies in Tanzania have adopted the three long-term impact results of zero new infections, zero HIV deaths and zero stigma and discrimination. Strategies to reach these results include scaling-up HIV Testing and Counselling (HTC); Preventing Mother-To-Child Transmission (PMTCT); and strengthening Care and Treatment Clinic (CTC) services. Previous studies showed that HIV policy and guideline recommendations were not always implemented in rural South Tanzania. This study aims to identify the determinants of HIV guideline implementation. A qualitative study of 23 semi-structured interviews with facility in-charges; healthcare workers; district, regional and national HIV coordinators was conducted. Five health facilities were purposively selected by level, ownership and proximity to district headquarters. Interviews were analysed according to Fleuren's five determinants of innovation uptake related to: strategies used in guideline development and dissemination; guideline characteristics; the guideline implementing organization; guideline users; and the socio-cultural and regulatory context. None of the facilities had the HTC national guideline document. Non-involvement of providers in revisions and weak planning for guideline dissemination impeded their implementation. Lengthy guidelines and those written in English were under-used, and activities perceived to be complicated, like WHO-staging, were avoided. Availability of staff and lack of supplies like test kits and medication impeded implementation. Collaboration between facilities enhanced implementation, as did peer-support among providers. Provider characteristics including education level, knowledge of, and commitment to the guideline influenced implementation. According to providers, determinants of clients' service use included gender norms, stigma, trust and perceived benefits. The regulatory context prohibited private hospitals from buying HIV supplies. Being tools for bringing policies to practice, national guidelines are crucial in the efforts towards the three zeros. Strategies to improve providers' adherence to guidelines should include development of clearer guideline dissemination plans, strengthening of the health system, and possibly addressing of provider-perceived patient-level barriers to utilizing HIV services.

Identifying gaps in HIV service delivery across the diagnosis-to-treatment cascade: findings from health facility surveys in six sub-Saharan countries.

INTRODUCTION: Despite the rollout of antiretroviral therapy (ART), challenges remain in ensuring timely access to care and treatment for people living with HIV. As part of a multi-country study to investigate HIV mortality, we conducted health facility surveys within 10 health and demographic surveillance system sites across six countries in Eastern and Southern Africa to investigate clinic-level factors influencing (i) use of HIV testing services, (ii) use of HIV care and treatment and (iii) patient retention on ART. METHODS: Health facilities (n = 156) were sampled within 10 surveillance sites: Nairobi and Kisumu (Kenya), Karonga (Malawi), Agincourt and uMkhanyakude (South Africa), Ifakara and Kisesa (Tanzania), Kyamulibwa and Rakai (Uganda) and Manicaland (Zimbabwe). Structured questionnaires were administered to in-charge staff members of HIV testing, prevention of mother-to-child transmission (PMTCT) and ART units within the facilities. Forty-one indicators influencing uptake and patient retention along the continuum of HIV care were compared across sites using descriptive statistics. RESULTS: The number of facilities surveyed ranged from six in Malawi to 36 in Zimbabwe. Eighty percent were government-run; 73% were lower-level facilities and 17% were district/referral hospitals. Client load varied widely, from less than one up to 65 HIV testing clients per provider per week. Most facilities (>80%) delivered services or interventions that would support patient retention in care such as delivering free services, offering PMTCT within antenatal care, pre-ART monitoring and adherence counselling. Many facilities under-delivered in several areas, however, such as targeted testing for high-risk groups (21%) and mobile testing (36%). There were also intra-site and inter-site differences, including in the delivery of Option B+ (ranging from 6% in Kisumu to 93% in Kyamulibwa), and nurse-led ART initiation (ranging from 50% in Kisesa to 100% in Karonga and Agincourt). Only facilities in Malawi did not require additional lab tests for ART initiation. Stock-outs of HIV test kits and antiretroviral drugs were particularly common in Tanzania. CONCLUSION: We identified a high standard of health facility performance in delivering strategies that may support progression through the continuum of HIV care. HIV testing policy and practice was particularly weak. Inter- and intra-country differences in quality and coverage represent opportunities to improve the delivery of comprehensive services to people living with HIV.

Perceptions on diabetes care provision among health providers in rural Tanzania: a qualitative study.

Diabetes prevalence in Tanzania was estimated at 9.1% in 2012 among adults aged 24-65 years - higher than the HIV prevalence in the general population at that time. Health systems in lower- and middle-income countries are not designed for chronic health care, yet the rising burden of non-communicable diseases such as diabetes demands chronic care services. To inform policies on diabetes care, we conducted a study on the health services in place to diagnose, treat and care for diabetes patients in rural Tanzania. The study was an exploratory and descriptive study involving qualitative methods (in-depth interviews, observations and document reviews) and was conducted in a rural district in Tanzania. Fifteen health providers in four health facilities at different levels of the health care system were interviewed. The health care organization elements of the Innovative Care for Chronic Conditions (ICCC) framework were used to guide assessment of the diabetes services in the district. We found that diabetes care in this district was centralized at the referral and district facilities, with unreliable supply of necessary commodities for diabetes care and health providers who had some knowledge of what was expected of them but felt ill-prepared for diabetes care. Facility and district level guidance was lacking and the continuity of care was broken within and between facilities. The HMIS could not produce reliable data on diabetes. Support for self-management to patients and their families was weak at all levels. In conclusion, the rural district we studied did not provide diabetes care close to the patients. Guidance on diabetes service provision and human resource management need strengthening and policies related to task-shifting need adjustment to improve quality of service provision for diabetes patients in rural settings.

"I don't have options but to persevere." Experiences and practices of care for HIV and diabetes in rural Tanzania: a qualitative study of patients and family caregivers.

BACKGROUND: The high prevalence of chronic diseases in Tanzania is putting a strain on the already stretched health care services, patients and their families. This study sought to find out how health care for diabetes and HIV is perceived, practiced and experienced by patients and family caregivers, to inform strategies to improve continuity of care. METHODS: Thirty two in-depth interviews were conducted among 19 patients (10 HIV, 9 diabetes) and 13 family caregivers (6 HIV, 7 diabetes). Diabetes patients and caregivers were accessed through one referral facility. HIV patients and caregivers were accessed through HIV clinics at the district hospital, one health centre and one dispensary respectively. The innovative care for chronic conditions framework informed the study design. Data was analysed with the help of Nvivo 10. RESULTS: Three major themes emerged; preparedness and practices in care, health care at health facilities and community support in care for HIV and diabetes. In preparedness and practices, HIV patients and caregivers knew more about aspects of HIV than did diabetes patients and caregivers on diabetes aspects. Continued education on care for the conditions was better structured for HIV than diabetes. On care at facilities, HIV and diabetes patients reported that they appreciated familiarity with providers, warm reception, gentle correction of mistakes and privacy during care. HIV services were free of charge at all levels. Costs involved in seeking services resulted in some diabetes patients to not keep appointments. There was limited community support for care of diabetes patients. Community support for HIV care was through community health workers, patient groups, and village leaders. CONCLUSION: Diabetes and HIV have socio-cultural and economic implications for patients and their families. The HIV programme is successfully using decentralization of health services, task shifting and CHWs to address these implications. For diabetes and NCDs, decentralization and task shifting are also important and, strengthening of community involvement is warranted for continuity of care and patient centeredness in care. While considering differences between HIV and diabetes, we have shown that Tanzania's rich experiences in community involvement in health can be leveraged for care and treatment of diabetes and other NCDs.

A comparative analysis of national HIV policies in six African countries with generalized epidemics.

OBJECTIVE: To compare national human immunodeficiency virus (HIV) policies influencing access to HIV testing and treatment services in six sub-Saharan African countries. METHODS: We reviewed HIV policies as part of a multi-country study on adult mortality in sub-Saharan Africa. A policy extraction tool was developed and used to review national HIV policy documents and guidelines published in Kenya, Malawi, South Africa, Uganda, the United Republic of Tanzania and Zimbabwe between 2003 and 2013. Key informant interviews helped to fill gaps in findings. National policies were categorized according to whether they explicitly or implicitly adhered to 54 policy indicators, identified through literature and expert reviews. We also compared the national policies with World Health Organization (WHO) guidance. FINDINGS: There was wide variation in policies between countries; each country was progressive in some areas and not in others. Malawi was particularly advanced in promoting rapid initiation of antiretroviral therapy. However, no country had a consistently enabling policy context expected to increase access to care and prevent attrition. Countries went beyond WHO guidance in certain areas and key informants reported that practice often surpassed policy. CONCLUSION: Evaluating the impact of policy differences on access to care and health outcomes among people living with HIV is challenging. Certain policies will exert more influence than others and official policies are not always implemented. Future research should assess the extent of policy implementation and link these findings with HIV outcomes.

Public policy, health system, and community actions against illness as platforms for response to NCDs in Tanzania: a narrative review.

BACKGROUND: Most low- and middle- income countries are facing a rise of the burden of non-communicable diseases (NCDs) alongside the persistent burden of infectious diseases. This narrative review aims to provide an inventory of how the existing policy environment, health system, and communities are addressing the NCDs situation in Tanzania and identify gaps for advancing the NCD research and policy agenda. METHODOLOGY: A literature search was performed on PubMed and Google scholar with full text retrieval from HINARI of English language articles published between 2000 and 2012. Documents were read to extract information on what Tanzanian actors were doing that contributed to NCDs prevention, treatment, and control, and a narration was written out of these. Reference lists of all retrieved articles were searched for additional relevant articles. Websites of organizations active in the field of NCDs including the Government of Tanzania and WHO were searched for reports and grey literature. RESULTS: Lack of a specific and overarching NCD policy has slowed and fragmented the implementation of existing strategies to prevent and control NCDs and their determinants. The health system is not prepared to deal with the rising NCD burden although there are random initiatives to improve this situation. How the community is responding to these emerging conditions is still unknown, and the current health-seeking behavior and perceptions on the risk factors may not favor control of NCDs and their risk factors. CONCLUSION AND RECOMMENDATION: There is limited information on the burden and determinants of NCDs to inform the design of an integrative and multisectorial policy. Evidence on effective interventions for NCD services in primary care levels and on community perceptions on NCDs and their care seeking is virtually absent. Research and public health interventions must be anchored in the policy, health system, and community platforms for a holistic response.

Challenges in providing counselling to MSM in highly stigmatized contexts: results of a qualitative study from Kenya.

The role of men who have sex with men (MSM) in the African HIV epidemic is gaining recognition yet capacity to address the HIV prevention needs of this group is limited. HIV testing and counselling is not only a critical entry point for biomedical HIV prevention interventions, such as pre-exposure prophylaxis, rectal microbicides and early treatment initiation, but is also an opportunity for focused risk reduction counselling that can support individuals living in difficult circumstances. For prevention efforts to succeed, however, MSM need to access services and they will only do so if these are non-judgmental, informative, focused on their needs, and of clear benefit. This study aimed to understand Kenyan providers' attitudes towards and experiences with counselling MSM in a research clinic targeting this group for HIV prevention. We used in-depth interviews to explore values, attitudes and cognitive and social constructs of 13 counsellors and 3 clinicians providing services to MSM at this clinic. Service providers felt that despite their growing experience, more targeted training would have been helpful to improve their effectiveness in MSM-specific risk reduction counselling. They wanted greater familiarity with MSM in Kenya to better understand the root causes of MSM risk-taking (e.g., poverty, sex work, substance abuse, misconceptions about transmission, stigma, and sexual desire) and felt frustrated at the perceived intractability of some of their clients' issues. In addition, they identified training needs on how to question men about specific risk behaviours, improved strategies for negotiating risk reduction with counselling clients, and improved support supervision from senior counsellors. This paper describes the themes arising from these interviews and makes practical recommendations on training and support supervision systems for nascent MSM HIV prevention programmes in Africa.

High HIV-1 incidence, correlates of HIV-1 acquisition, and high viral loads following seroconversion among MSM.

BACKGROUND: HIV-1 incidence estimates and correlates of HIV-1 acquisition in African MSM are largely unknown. METHODS: Since 2005, HIV-1-uninfected men who reported sex with men and women (MSMW) or sex with men exclusively (MSME) were followed at scheduled visits for collection of behavioural and clinical examination data and plasma for HIV-1 testing. Urethral or rectal secretions were collected from symptomatic men to screen for gonorrhoea. Poisson regression methods were used to estimate adjusted incidence rate ratios to explore associations between risk factors and incident HIV-1 infection. Plasma viral loads (PVLs) were assessed over 2 years following seroconversion. RESULTS: Overall HIV-1 incidence in 449 men was 8.6 [95% confidence interval (CI) 6.7-11.0] per 100 person-years. Incidence was 5.8 (95% CI 4.2-7.9) per 100 person-years among MSMW, and 35.2 (95% CI 23.8-52.1) per 100 person-years among MSME. Unprotected sex, receptive anal intercourse, exclusive sex with men, group sex, and gonorrhoea in the past 6 months were strongly associated with HIV-1 acquisition, adjusted for confounders. PVL in seroconverters was more than 4 log10 copies/ml at 230 (73.4%) of 313 visits in MSMW and 153 (75.0%) of 204 visits in MSME. CONCLUSION: HIV-1 incidence is very high among MSM in coastal Kenya, and many seroconverters maintain high PVL for up to 2 years after infection. Effective HIV-1 prevention interventions, including treatment as prevention, are urgently needed in this population.

Identifying at-risk populations in Kenya and South Africa: HIV incidence in cohorts of men who report sex with men, sex workers, and youth.

OBJECTIVE: To identify and describe populations at risk for HIV in 3 clinical research centers in Kenya and South Africa. DESIGN: Prospective cohort study. METHODS: Volunteers reporting recent sexual activity, multiple partners, transactional sex, sex with an HIV-positive partner, or, if male, sex with men (MSM; in Kenya only) were enrolled. Sexually active minors were enrolled in South Africa only. Risk behavior, HIV testing, and clinical data were obtained at follow-up visits. RESULTS: From 2005 to 2008, 3023 volunteers were screened, 2113 enrolled, and 1834 contributed data on HIV incidence. MSM had the highest HIV incidence rate of 6.8 cases per 100 person-years [95% confidence interval (CI): 4.9 to 9.2] followed by women in Kilifi and Cape Town (2.7 cases per 100 person-years, 95% CI: 1.7 to 4.2). No seroconversions were observed in Nairobi women or men in Nairobi or Cape Town who were not MSM. In 327 MSM, predictors of HIV acquisition included report of genital ulcer (Hazard Ratio: 4.5, 95% CI: 1.7 to 11.6), not completing secondary school education (HR: 3.4, 95% CI: 1.6 to 7.2) and reporting receptive anal intercourse (HR: 8.2, 95% CI: 2.7 to 25.0). Paying for sex was inversely associated with HIV infection (HR: 0.2, 95% CI: 0.04 to 0.8). 279 (13.0%) volunteers did not return after the first visit; subsequent attrition rates ranged from 10.4 to 21.8 volunteers per 100 person-years across clinical research centers. CONCLUSIONS: Finding, enrolling, and retaining risk populations for HIV prevention trials is challenging in Africa. African MSM are not frequently engaged for research, have high HIV incidence, need urgent risk reduction counseling, and may represent a suitable population for future HIV prevention trials.

Most adults seek urgent healthcare when acquiring HIV-1 and are frequently treated for malaria in coastal Kenya.

BACKGROUND: Acute HIV-1 infection (AHI) may present with symptoms for which urgent healthcare is sought. However, little is known about healthcare seeking around the time of HIV-1 seroconversion in sub-Saharan Africa. METHODS: Review of clinical, counselling, treatment and laboratory records of previously HIV-1 seronegative at-risk adults, followed at monthly or 3-monthly visits, who seroconverted and enrolled in an AHI cohort. All HIV-seronegative plasma samples were tested for p24 antigen (p24) and stored preseroconversion samples for HIV-1 RNA (RNA). Factors associated with malaria treatment while acquiring HIV-1 were evaluated in multiple logistic regression. RESULTS: Sixty men and 12 women (95% of 75 seroconverters) were evaluated, including 43 (60%) with either p24-positive or RNA-positive or HIV-1 discordant rapid antibodies prior to seroconversion. Prior to diagnosis, 54 patients (75%) reported fever and 50 (69%) sought urgent care for symptomatic illness, including 23 (32%) who sought care in a nonresearch setting. Twenty-nine patients (40%) received presumptive malaria treatment. Only 24% of febrile patients were tested for malaria parasites. All documented smear results were negative. Malaria treatment was strongly associated with fever [adjusted odds ratio (aOR): 46, 95% confidence interval (CI): 3-725] and nonresearch setting (aOR: 5, 95% CI: 3-64). AHI was suspected in six (12%) patients who presented for urgent care during research evaluation. CONCLUSIONS: The majority of adults with AHI seek urgent healthcare. These individuals are often presumptively treated for malaria. Improved recognition of AHI in adults presenting for care may offer opportunities for optimizing HIV prevention strategies.

Transmitted HIV type 1 drug resistance among individuals with recent HIV infection in East and Southern Africa.

To characterize WHO-defined transmitted HIV drug resistance mutation (TDRM) data from recently HIV-infected African volunteers, we sequenced HIV (pol) and evaluated for TDRM the earliest available specimens from ARV-naive volunteers diagnosed within 1 year of their estimated date of infection at eight research centers in sub-Saharan Africa. TDRMs were detected in 19/408 (5%) volunteers. The prevalence of TDRMs varied by research center, from 5/26 (19%) in Entebbe, 6/78 (8%) in Kigali, 2/49 (4%) in Kilifi, to 3/106 (3%) in Lusaka. One of five volunteers from Cape Town (20%) had TDRMs. Despite small numbers, our data suggest an increase in DRMs by year of infection in Zambia (p = 0.004). The prevalence observed in Entebbe was high across the entire study. ARV history data from 12 (63%) HIV-infected sexual partners were available; 3 reported ARV use prior to transmission. Among four partners with sequence data available, transmission linkage was confirmed and two had the same TDRMs as the newly infected volunteer (both K103N). As ARV therapy continues to increase in availability throughout Africa, monitoring incident virus strains for the presence of TDRMs should be a priority. Early HIV infection cohorts provide an excellent and important platform to monitor the development of TDRMs to inform treatment guidelines, drug choices, and strategies for secondary prevention of TDRM transmission.

Evaluation of HIV type 1 strains in men having sex with men and in female sex workers in Mombasa, Kenya.

We compared HIV-1 strains in incident and prevalent infections in a cohort of men having sex with men (MSM) and female sex workers (FSW) near Mombasa, Kenya and conducted a cross-sectional study of viral isolates from a sample of HIV-1-infected MSM and FSW in Kilifi, Coast Province, Kenya. RNA extracted from plasma of 13 MSM, 9 FSW, and one heterosexual male was amplified by nested RT-PCR and the products were directly sequenced. HIV-1 strains from 21 individuals were characterized with one or more complete genome sequences, and two were sequenced in the Nef gene. The envelope quasispecies was also studied in one individual. Among MSM, eight strains were subtype A and five were recombinant. There were two epidemiologically linked pairs of sequences; one pair was subtype A and the other pair was a complex AA2CD recombinant of identical structure. Another MSM was dually infected with DG recombinant strains of related, but nonidentical, structure. MSM also harbored AC and AD recombinant strains. The FSW harbored seven subtype A strains, an AD recombinant, and an AA2D strain related to CRF16_A2D. The one heterosexual male studied had a subtype A infection. This MSM epidemic in Kenya appears to be of local origin, harboring many strains typical of the broader Kenyan epidemic. Characteristics of a close social network were identified, with extended chains of transmission, novel recombinant strains possibly generated within the network, and a relatively high proportion of recombinant and dual infections.

CLSI-derived hematology and biochemistry reference intervals for healthy adults in eastern and southern Africa.

BACKGROUND: Clinical laboratory reference intervals have not been established in many African countries, and non-local intervals are commonly used in clinical trials to screen and monitor adverse events (AEs) among African participants. Using laboratory reference intervals derived from other populations excludes potential trial volunteers in Africa and makes AE assessment challenging. The objective of this study was to establish clinical laboratory reference intervals for 25 hematology, immunology and biochemistry values among healthy African adults typical of those who might join a clinical trial. METHODS AND FINDINGS: Equal proportions of men and women were invited to participate in a cross sectional study at seven clinical centers (Kigali, Rwanda; Masaka and Entebbe, Uganda; two in Nairobi and one in Kilifi, Kenya; and Lusaka, Zambia). All laboratories used hematology, immunology and biochemistry analyzers validated by an independent clinical laboratory. Clinical and Laboratory Standards Institute guidelines were followed to create study consensus intervals. For comparison, AE grading criteria published by the U.S. National Institute of Allergy and Infectious Diseases Division of AIDS (DAIDS) and other U.S. reference intervals were used. 2,990 potential volunteers were screened, and 2,105 (1,083 men and 1,022 women) were included in the analysis. While some significant gender and regional differences were observed, creating consensus African study intervals from the complete data was possible for 18 of the 25 analytes. Compared to reference intervals from the U.S., we found lower hematocrit and hemoglobin levels, particularly among women, lower white blood cell and neutrophil counts, and lower amylase. Both genders had elevated eosinophil counts, immunoglobulin G, total and direct bilirubin, lactate dehydrogenase and creatine phosphokinase, the latter being more pronounced among women. When graded against U.S. -derived DAIDS AE grading criteria, we observed 774 (35.3%) volunteers with grade one or higher results; 314 (14.9%) had elevated total bilirubin, and 201 (9.6%) had low neutrophil counts. These otherwise healthy volunteers would be excluded or would require special exemption to participate in many clinical trials. CONCLUSIONS: To accelerate clinical trials in Africa, and to improve their scientific validity, locally appropriate reference ranges should be used. This study provides ranges that will inform inclusion criteria and evaluation of adverse events for studies in these regions of Africa.