Fever is typically treated empirically in rural Mozambique. We examined the distribution and antimicrobial susceptibility patterns of bacterial pathogens isolated from blood-culture specimens, and clinical characteristics of ambulatory HIV-infected febrile patients with and without bacteremia. This analysis was nested within a larger prospective observational study to evaluate the performance of new Mozambican guidelines for fever and anemia in HIV-infected adults (clinical trial registration NCT01681914, www.clinicaltrials.gov); the guidelines were designed to be used by non-physician clinicians who attended ambulatory HIV-infected patients in very resource-constrained peripheral health units. In 2012 (April-September), we recruited 258 HIV-infected adults with documented fever or history of recent fever in three sites within Zambézia Province, Mozambique. Although febrile patients were routinely tested for malaria, blood culture capacity was unavailable in Zambézia prior to study initiation. We confirmed bacteremia in 39 (15.1%) of 258 patients. The predominant organisms were non-typhoid Salmonella, nearly all resistant to multiple first-line antibiotics (ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole). Features most associated with bacteremia included higher temperature, lower CD4+ T-lymphocyte count, lower hemoglobin, and headache. Introduction of blood cultures allowed us to: 1) confirm bacteremia in a substantial proportion of patients; 2) tailor specific antimicrobial therapy for confirmed bacteremia based on known susceptibilities; 3) make informed choices of presumptive antibiotics for patients with suspected bacteremia; and 4) construct a preliminary clinical profile to help clinicians determine who would most likely benefit from presumptive bacteremia treatment. Our findings demonstrate that in resource-limited settings, there is urgent need to expand local microbiologic capacity to better identify and treat cases of bacteremia in HIV-infected and other patients, and to support surveillance. Data on the prevalence and susceptibility patterns of important pathogens can guide national formulary and prescribing practices.

Mozambique's updated guideline for management of HIV-associated anemia prompts clinicians to consider opportunistic conditions, adverse drug reactions, and untreated immunosuppression in addition to iron deficiency, intestinal helminthes, and malaria. We prospectively evaluated this guideline in rural Zambézia Province. Likely cause(s) of anemia were determined through prespecified history, physical examination, and laboratory testing. Diagnoses were ''etiologic'' if laboratory confirmed (sputum microscopy, blood culture, Plasmodium falciparum malaria rapid test) or ''syndromic'' if not. To assess hemoglobin response, we used serial point-of-care measurements. We studied 324 ambulatory, anemic (hemoglobin <10 g/dl) HIV-infected adults. Study clinicians treated nearly all [315 (97.2%)] for suspected iron deficiency and/or helminthes; 56 (17.3%) had laboratory-confirmed malaria. Other assigned diagnoses included tuberculosis [30 (9.3%)], adverse drug reactions [26 (8.0%)], and bacteremia [13 (4.1%)]. Etiologic diagnosis was achieved in 79 (24.4%). Of 169 (52.2%) subjects who improved (hemoglobin increase of ‡1 g/dl without indications for hospitalization), only 65 (38.5%) received conventional management (iron supplementation, deworming, and/or antimalarials) alone. Thirty (9.3%) died and/or were hospitalized, and 125 (38.6%) were lost to follow-up. Multivariable linear and logistic regression models described better hemoglobin responses and/or outcomes in subjects with higher CD4 + T-lymphocyte counts, pre-enrollment antiretroviral therapy and/or co-trimoxazole prophylaxis, discontinuation of zidovudine for suspected adverse reaction, and smear-positive tuberculosis. Adverse outcomes were associated with fever, low body mass index, bacteremia, esophageal candidiasis, and low or missing CD4 + T cell counts. In this severely resource-limited setting, successful anemia management often required interventions other than conventional presumptive treatment, thus supporting Mozambique's guideline revision.

One of most intriguing features of the HIV-1 subtype B epidemic in Brazil is the high frequency of isolates exhibiting tryptophan (W) in the tetramer (GWGR) at the tip of the V3 loop. We observed that the frequencies of glutamic and aspartic acids at site 25 of the V3 loop are quite distinct in GWGR isolates compared with viruses with other tetramers. The basic amino acids at sites 11 and 25 of V3 are strongly linked with CCR5-to-CXCR4 coreceptor shift. We therefore predicted phenotype usage and found that GWGR isolates are exclusively CCR5-using. Further evidence of this came from intrahost sequences, where basic amino acid substitutions at sites 11 and 25 emerged only in isolates presenting a tryptophan-to-glycine replacement at the tetramer of the V3. In addition, modeled 3D-structures of the V3 loop of GWGR and GGGR in intrahost viruses differ essentially in the binding region of the coreceptor.

Background: The first pillar of the UNAIDS 90-90-90 goal seeks to accurately identify persons living with HIV (PLHIV), a process that is predicated on facilities having the necessary HIV tests available to perform the task. In many rural settings, the identification of PLHIV is accomplished through a two-step process involving the sequential use of 2 separate rapid diagnostic tests (RDTs). Inadequate inventory of either test has ramifications for the success of HIV-related programs. The purpose of this study was to evaluate the inventory levels of HIV RDT kits at specific healthcare facilities in Zambézia province, Mozambique. Methods: Using facility-level pharmacy stock surveillance data from October 2015 through September 2016, we assessed the inventory levels of HIV RDTs at 75 health facilities in 8 districts within Zambézia province, Mozambique. Using programmatically established categories (good, sufficient, threatened, or stockout), defined in conjunction with the provincial health authorities, descriptive statistics were performed to determine inventory control of HIV RDTs at the district and health facility levels. Monthly proportions of adequate (good + sufficient) inventory were calculated for each district to identify inventory trends over the evaluation period. To assess whether the proportion of inadequate stocks differed between RDT, a mixed-effects logistic regression was conducted, with inadequate inventory status as the outcome of interest. Results: When viewed as a whole, the inventory of each test kit was reported as being at adequate levels more than 89% of the time across the 75 facilities. However, disaggregated analysis revealed significant variability in the inventory levels of HIV RDTs at the district level. Specifically, the districts of Inhassunge, Namacurra, and Pebane reported inadequate inventory levels (threatened + stockout), of one or both test kits, for more than 10% of the study period. In addition, a disparity between inventory levels of each test kit was identified, with the odds of reporting inadequate inventory levels of the confirmatory test (Uni-Gold™) being approximately 1.8-fold greater than the initial test (Determine™) (odds ratio: 1.82, 95% CI: 1.40-2.38). Conclusion: As Test and Treat programs evolve, a significant emphasis should be placed on the "test" component of the strategy, beginning with assurances that health facilities have the adequate inventory of RDT necessary to meet the needs of their community. As national policy-makers rely predominantly on data from the upstream arm of the supply chain, it is unlikely the disparity between inventory levels of HIV RDTs identified at individual districts and specific health facilities would have been recognized. Moving forward, our findings point to a need for (1) renewed efforts reinforcing appropriate downstream forecasting of essential medicines and diagnostic tests in general and for Uni-Gold™ test kits specifically, and (2) simple metrics that may be routinely collected at all health facilities and which may then easily and quickly flow upstream so that policy-makers may optimally allocate resources.