To determine the role of primary antifungal prophylaxis in the prevention of cryptococcal meningitis and all-cause mortality in advanced HIV infection. This was a systematic review and meta-analysis of randomized trials and observational studies. Google Scholar™, PubMed and Embase databases were searched for relevant studies. Quality was assessed using different criteria, depending on study type. Publication bias was assessed and subgroup and sensitivity analyses were performed. When the results of the meta-analysis were homogeneous, the fixed-effects model was used; when the results of the meta-analysis were heterogenous, the random effects model was used. Primary prophylaxis prevented cryptococcal meningitis but did not confer protection against overall mortality, although there was evidence of a reduction in cryptococcal-specific mortality in resource-limited settings. Primary antifungal prophylaxis should be recommended in patients with advanced HIV infection in resource-limited settings with a high incidence of cryptococcal meningitis.

AbstractBackgroundThe malaria test positivity rate (TPR) is increasingly used as an indicator of malaria morbidity because TPR is based on laboratory-confirmed cases and is simple to incorporate into existing surveillance systems. However, temporal trends in TPR may reflect changes in factors associated with malaria rather than true changes in malaria morbidity. This study examines the effects of age, area of residence and diagnostic test on TPR at two health facilities in regions of Uganda with differing malaria endemicity.MethodsThe analysis included data from diagnostic blood smears performed at health facilities in Walukuba and Aduku between January 2009 and December 2010. The associations between age and time and between age and TPR were evaluated independently to determine the potential for age to confound temporal trends in TPR. Subsequently, differences between observed TPR and TPR adjusted for age were compared to determine if confounding was present. A similar analysis was performed for area of residence. Temporal trends in observed TPR were compared to trends in TPR expected using rapid diagnostic tests, which were modelled based upon sensitivity and specificity in prior studies.ResultsAge was independently associated with both TPR and time at both sites. At Aduku, age-adjusted TPR increased relative to observed TPR due to the association between younger age and TPR and the gradual increase in age distribution. At Walukuba, there were no clear differences between observed and age-adjusted TPR. Area of residence was independently associated with both TPR and time at both sites, though there were no clear differences in temporal trends in area of residence-adjusted TPR and observed TPR at either site. Expected TPR with pLDH- and HRP-2-based rapid diagnostic tests (RDTs) was higher than observed TPR at all time points at both sites.ConclusionsAdjusting for potential confounders such as age and area of residence can ensure that temporal trends in TPR due to confounding are not mistakenly ascribed to true changes in malaria morbidity. The potentially large effect of diagnostic test on TPR can be accounted for by calculating and adjusting for the sensitivity and specificity of the test used.

PURPOSE OF REVIEW:There is an urgent need to understand new population-level approaches that achieve high levels of treatment and viral suppression for persons living with HIV. RECENT FINDINGS:The SEARCH Universal test and treat (UTT) trial conducted in Kenya and Uganda aimed to reduce HIV incidence and improve community health. SEARCH offered HIV and multidisease testing at health fairs followed by home testing for nonparticipants in 32 communities, each with approximately 10 000 persons. In the 16 intervention communities, UNAIDS 90-90-90 targets were achieved within 3 years, reaching '92-95-90' and 79% population-level viral suppression. HIV incidence declined by 32% between year 1 and 3 of follow-up. Key principles of SEARCH's approach included community engagement, integration of HIV with multidisease services, rapid ART start upon HIV diagnosis, and patient-centered, streamlined care. SEARCH's community health approach also reduced HIV mortality, annual TB incidence, and uncontrolled hypertension compared with a country standard of care. Population-level viral suppression increased beyond the UNAIDS 73% target in women and men and reached levels well above recent country estimates across much of sub-Saharan Africa. SUMMARY:SEARCH provides one example of how to rapidly surpass UNAIDS 90-90-90 targets while addressing community health on the path to HIV epidemic control.

Abstract Background Malaria, malnutrition and anaemia are major causes of morbidity and mortality in African children. The interplay between these conditions is complex and limited data exist on factors associated with these conditions among infants born to HIV-uninfected and infected women. Methods Two hundred HIV-exposed (HIV-uninfected infants born to HIV-infected mothers) and 400 HIV-unexposed infants were recruited from an area of high malaria transmission in rural Uganda. A cross-sectional survey was performed at enrolment to measure the prevalence of malaria parasitaemia, measures of malnutrition (z-scores <2 standard deviations below mean) and anaemia (haemoglobin <8 gm/dL). Multivariate logistic regression was used to measure associations between these conditions and risk factors of interest including household demographics, malaria prevention practices, breastfeeding practices, household structure and wealth index. Results The prevalence of malaria parasitaemia was 20%. Factors protective against parasitaemia included female gender (OR = 0.66, p = 0.047), mother’s age (OR = 0.81 per five-year increase, p = 0.01), reported bed net use (OR = 0.63, p = 0.03) and living in a well-constructed house (OR = 0.25, p = 0.01). Although HIV-unexposed infants had a higher risk of parasitaemia compared to HIV-exposed infants (24% vs 14%, p = 0.004), there was no significant association between HIV-exposure status and parasitaemia after controlling for the use of malaria preventative measures including bed net use and trimethoprim-sulphamethoxazole prophylaxis. The prevalence of stunting, underweight, and wasting were 10%, 7%, and 3%, respectively. HIV-exposed infants had a higher odds of stunting (OR = 2.23, p = 0.005), underweight (OR = 1.73, p = 0.09) and wasting (OR = 3.29, p = 0.02). The prevalence of anaemia was 12%. Risk factors for anaemia included older infant age (OR = 2.05 per one month increase, p = 0.003) and having malaria parasitaemia (OR = 5.74, p < 0.001). Conclusions Compared to HIV-unexposed infants, HIV-exposed infants had a higher use of malaria preventative measures and lower odds of malaria parasitaemia. Having a better constructed house was also protective against malaria parasitaemia. HIV-exposure was the primary risk factor for measures of malnutrition. The primary risk factor for anaemia was malaria parasitaemia. These findings suggest the need to better target existing interventions for malaria, malnutrition and anaemia as well as the need to explore further the mechanisms behind the observed associations.

Purpose of review

The growing burden of untreated chronic disease among persons with HIV (PWH) threatens to reverse heath gains from ART expansion. Universal test and treat (UTT)'s population-based approach provides opportunity to jointly identify and treat HIV and other chronic diseases. This review's purpose is to describe SEARCH UTT study's integrated disease strategy and related approaches in Sub-Saharan Africa.

Recent findings

In SEARCH, 97% of adults were HIV tested, 85% were screened for hypertension, and 79% for diabetes at health fairs after 2 years, for an additional $1.16/person. After 3 years, population-level hypertension control was 26% higher in intervention versus control communities. Other mobile/home-based multi-disease screening approaches have proven successful, but data on multi-disease care delivery are extremely limited and show little effect on clinical outcomes. Integration of chronic disease into HIV in the UTT era is feasible and can achieve population level effects; however, optimization and implementation remain a huge unmet need.

Purpose of review

There is an urgent need to understand new population-level approaches that achieve high levels of treatment and viral suppression for persons living with HIV.

Recent findings

The SEARCH Universal test and treat (UTT) trial conducted in Kenya and Uganda aimed to reduce HIV incidence and improve community health. SEARCH offered HIV and multidisease testing at health fairs followed by home testing for nonparticipants in 32 communities, each with approximately 10 000 persons. In the 16 intervention communities, UNAIDS 90-90-90 targets were achieved within 3 years, reaching '92-95-90' and 79% population-level viral suppression. HIV incidence declined by 32% between year 1 and 3 of follow-up. Key principles of SEARCH's approach included community engagement, integration of HIV with multidisease services, rapid ART start upon HIV diagnosis, and patient-centered, streamlined care. SEARCH's community health approach also reduced HIV mortality, annual TB incidence, and uncontrolled hypertension compared with a country standard of care. Population-level viral suppression increased beyond the UNAIDS 73% target in women and men and reached levels well above recent country estimates across much of sub-Saharan Africa.

Summary

SEARCH provides one example of how to rapidly surpass UNAIDS 90-90-90 targets while addressing community health on the path to HIV epidemic control.

HIV infection affects the clinical pattern of malaria. There is emerging evidence to suggest that previously documented interactions may be modified by recently scaled-up HIV and malaria interventions. Prophylaxis with trimethoprim-sulfamethoxazole (TS) in combination with use of insecticide-treated nets can markedly decrease the incidence of malaria in HIV-infected pregnant and nonpregnant adults and children even in the setting of antifolate resistance-conferring mutations that are currently common in Africa. Nonetheless, additional interventions are needed to protect HIV-infected people that reside in high-malaria-transmission areas. Artemether-lumefantrine and dihydroartemisinin-piperaquine are highly efficacious and safe for the treatment of uncomplicated malaria in HIV-infected persons. Coadministration of antiretroviral and antimalarial drugs creates the potential for pharmacokinetic drug interactions that may increase (causing enhancement of malaria treatment efficacy and post-treatment prophylaxis and/or unanticipated toxicity) or reduce (creating risk for treatment failure) antimalarial drug exposure. Further studies are needed to elucidate potentially important pharmacokinetic interactions between commonly used antimalarials, antiretrovirals and TS and their clinical implications. Data on the benefits of long-term TS prophylaxis among HIV patients on antiretroviral therapy who have achieved immune-reconstitution are limited. Studies to address these questions are ongoing or planned, and the results should provide the evidence base required to guide the prevention and treatment of malaria in HIV-infected patients.

Abstract Background In Africa, inadequate health services contribute to the lack of progress on malaria control. Evidence of the impact of interventions to improve health services on population-level malaria indicators is needed. We are conducting a cluster-randomised trial to assess whether a complex intervention delivered at public health centres in Uganda improves health outcomes of children and treatment of malaria, as compared to the current standard of care. Methods/Design Twenty public health centres (level II and III) in Tororo district will be included; 10 will be randomly assigned to the intervention and 10 to control. Clusters will include households located within 2 km of health centres. The trial statistician will generate the random allocation sequence and assign clusters. Health centres will be stratified by level, and restricted randomisation will be employed to ensure balance on cluster location and size. Allocation will not be blinded. The intervention includes training in health centre management, fever case management with use of rapid diagnostic tests (RDTs) for malaria, and patient-centered services, and provision of artemether-lumefantrine (AL) and RDTs when stocks run low. The impact of the intervention on population-level health indicators will be assessed through community surveys conducted at baseline in randomly selected children from each cluster, and repeated annually for two years. The impact on individuals over time will be assessed in a cohort study of children recruited from households randomly selected per cluster. The impact on health centres will be assessed using patient exit interviews, monthly surveillance, and assessment of health worker knowledge and skills. The primary outcome is the prevalence of anaemia (haemoglobin <11.0 g/dL) in individual children under five measured in the annual community surveys. The primary analysis will be based on the cluster-level results. Discussion The PRIME trial findings will be supplemented by the PROCESS study, an evaluation of the process, context, and wider impact of the PRIME intervention which will be conducted alongside the main trial, together providing evidence of the health impact of a public sector intervention in Uganda. Trial registration and funding This trial is registered at Clinicaltrials.gov (NCT01024426) and is supported by the ACT Consortium.

There are limited data characterizing HIV retesting among high-risk adults in sub-Saharan Africa. From October-December 2018, we distributed recruitment cards offering health evaluations with HIV testing at venues frequented by individuals at-risk of HIV infection in Southwest Uganda. Those who attended were asked about their HIV testing history and risk factors: having >1 sexual partner, an HIV+ partner, STIs, and/or transactional sex. We defined "highest risk" as ≥3 risk factors and "frequent testing" as ≥3 tests within the past year. Of 1,777 cards distributed, 1,482 (83%) adults came to clinic: median age was 26(IQR: 22-31), 598 (40%) were men, and 334 (23%) were HIV+. Of 1,148 HIV-negative adults, 338 (29%) were highest risk and 205 (18%) were frequent testers. Frequent testing was similar in women (19%) and men (16%, p = 0.22). Among women, those at highest risk were more likely to report any testing (90% vs. 81%, p = 0.01) and frequent testing (25% vs. 18%, p = 0.06) than those at lower risk. Among men, any testing and frequent testing were similar between risk levels. Among adults recruited from high-risk venues in peri-urban Uganda, HIV risk behaviors were commonly reported, yet frequent retesting remained low. Interventions to promote retesting are needed, particularly among men.