Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania.

In settings with high tuberculosis (TB) endemicity, distinct genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC population in Dar es Salaam, Tanzania over a six-year period, using 1,082 unique patient-derived MTBC whole-genome sequences (WGS) and associated clinical data. We show that the TB epidemic in Dar es Salaam is dominated by multiple MTBC genotypes introduced to Tanzania from different parts of the world during the last 300 years. The most common MTBC genotypes deriving from these introductions exhibited differences in transmission rates and in the duration of the infectious period, but little differences in overall fitness, as measured by the effective reproductive number. Moreover, measures of disease severity and bacterial load indicated no differences in virulence between these genotypes during active TB. Instead, the combination of an early introduction and a high transmission rate accounted for the high prevalence of L3.1.1, the most dominant MTBC genotype in this setting. Yet, a longer co-existence with the host population did not always result in a higher transmission rate, suggesting that distinct life-history traits have evolved in the different MTBC genotypes. Taken together, our results point to bacterial factors as important determinants of the TB epidemic in Dar es Salaam.

Differences in neutralizing antibody sensitivities and envelope characteristics indicate distinct antigenic properties of Nigerian HIV-1 subtype G and CRF02_AG.

The magnitude of the HIV-1 epidemic in Nigeria is second only to the subtype C epidemic in South Africa, yet the subtypes prevalent in Nigeria require further characterization. A panel of 50 subtype G and 18 CRF02_AG Nigerian HIV-1 pseudoviruses (PSV) was developed and envelope coreceptor usage, neutralization sensitivity and cross-clade reactivity were characterized. These PSV were neutralized by some antibodies targeting major neutralizing determinants, but potentially important differences were observed in specific sensitivities (eg. to sCD4, MPER and V2/V3 monoclonal antibodies), as well as in properties such as variable loop lengths, number of potential N-linked glycans and charge, demonstrating distinct antigenic characteristics of CRF02_AG and subtype G. There was preferential neutralization of the matched CRF/subtype when PSV from subtype G or CRF02_AG were tested using pooled plasma. These novel Nigerian PSV will be useful to study HIV-1 CRF- or subtype-specific humoral immune responses for subtype G and CRF02_AG.

Limited emergence of resistance to integrase strand transfer inhibitors (INSTIs) in ART-experienced participants failing dolutegravir-based antiretroviral therapy: a cross-sectional analysis of a Northeast Nigerian cohort.

BACKGROUND: Due to the high prevalence of resistance to NNRTI-based ART since 2018, consolidated recommendations from the WHO have indicated dolutegravir as the preferred drug of choice for HIV treatment globally. There is a paucity of resistance outcome data from HIV-1 non-B subtypes circulating across West Africa. AIMS: We characterized the mutational profiles of persons living with HIV from a cross-sectional cohort in North-East Nigeria failing a dolutegravir-based ART regimen. METHODS: WGS of plasma samples collected from 61 HIV-1-infected participants following virological failure of dolutegravir-based ART were sequenced using the Illumina platform. Sequencing was successfully completed for samples from 55 participants. Following quality control, 33 full genomes were analysed from participants with a median age of 40 years and median time on ART of 9 years. HIV-1 subtyping was performed using SNAPPy. RESULTS: Most participants had mutational profiles reflective of exposure to previous first- and second-line ART regimens comprised NRTIs and NNRTIs. More than half of participants had one or more drug resistance-associated mutations (DRMs) affecting susceptibility to NRTIs (17/33; 52%) and NNRTIs (24/33; 73%). Almost a quarter of participants (8/33; 24.4%) had one or more DRMs affecting tenofovir susceptibility. Only one participant, infected with HIV-1 subtype G, had evidence of DRMs affecting dolutegravir susceptibility-this was characterized by the T66A, G118R, E138K and R263K mutations. CONCLUSIONS: This study found a low prevalence of resistance to dolutegravir; the data are therefore supportive of the continual rollout of dolutegravir as the primary first-line regimen for ART-naive participants and the preferred switch to second-line ART across the region. However, population-level, longer-term data collection on dolutegravir outcomes are required to further guide implementation and policy action across the region.

Factors associated with viral suppression among adults living with HIV on antiretroviral therapy in Nigeria: Analysis of a population-based survey, 2018.

OBJECTIVE: Viral load suppression (VLS) is critical in reducing morbidity and mortality associated with HIV as well as minimizing the likelihood of HIV transmission to uninfected persons. The objective of this study was to identify factors associated with VLS among people living with HIV (PLWH) on antiretroviral (ARV) therapy to inform HIV programme strategies in Nigeria. METHODS: Adult participants, aged 15-64 years, from the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS), who self-reported to be a PLWH or had detectable ARVs, were analysed to examine factors associated with VLS defined as HIV RNA <1000 copies/mL. NAIIS measured HIV prevalence, viral load, ARV and hepatitis B in PLWH. Logistic regression models were used and reported weighted prevalence. RESULTS: Of 1322 participants, 949 (68.25%) were women and 1287 (96.82%) had detectable ARVs. The median age was 39.31 [interquartile range (IQR): 31.47-47.63] years. Prevalence of VLS was 80.88%. Compared with participants with detectable ARVs, those with undetectable ARVs in their blood specimens had lower odds of VLS [adjusted odds ratio (aOR) = 0.24, 95% confidence interval (CI): 0.08-0.64). Coinfection with hepatitis B and nonnucleoside reverse transcriptase inhibitor metabolites were also associated with lower odds of VLS. Older people (45-54 vs 15-24 years) had increased odds of VLS (aOR = 2.81, 95% CI: 1.14-6.90). CONCLUSION: Young people and those with undetectable ARVs had lower odds of virological suppression. Targeted interventions focusing on young people and adherence to medication are needed to achieve the UNAIDS 95-95-95 goals for HIV epidemic control.

Prevalence and characteristics of metabolic syndrome and its components among adults living with and without HIV in Nigeria: a single-center study.

BACKGROUND: Persons living with HIV (PLHIV) now live longer due to effective combination antiretroviral therapy. However, emerging evidence indicates that they may be at increased risk for some cardiometabolic disorders. We compared the prevalence of metabolic syndrome (MetS) and its component disorders between persons living with and without HIV in Nigeria. METHODS: This was a cross-sectional analysis of baseline data from a prospective cohort study of non-communicable diseases among PLHIV along with age- and sex-matched persons without HIV (PWoH) at the University of Abuja Teaching Hospital Nigeria. We collected sociodemographic and clinical data, including anthropometric measures and results of relevant laboratory tests. MetS was defined using a modification of the third report of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) criteria. RESULTS: Of the 440 PLHIV and 232 PWoH, women constituted 50.5% and 51.3% respectively. The median age of the PLHIV was 45 years while that of the PWoH was 40 years. The prevalence of MetS was 30.7% (95% CI: 26.4%, 35.2%) and 22.8% (95% CI: 17.6%, 28.8%) among the PLHIV and PWoH respectively (P = 0.026). Independent associations were found for older age (P < 0.001), female sex (P < 0.001), family history of diabetes (P < 0.001), family history of hypertension (P = 0.013) and alcohol use (P = 0.015). The prevalence of component disorders for PLHIV versus PWoH were as follows: high blood pressure (22.3% vs 20.3%), prediabetes (33.8% vs 21.1%), diabetes (20.5% vs 8.2%), high triglycerides (24.5% vs 17.2%), low HDL-Cholesterol (51.1% vs 41.4%), and abdominal obesity (38.4% vs 37.1%). Adjusting for age and sex, prediabetes, diabetes, and low HDL-Cholesterol were significantly associated with HIV status. Duration on antiretroviral therapy, protease inhibitor-based regimen, CD4 count, and viral load were associated with some of the disorders mostly in unadjusted analyses. CONCLUSION: We found a high burden of MetS and its component disorders, with significantly higher prevalence of dysglycemia and dyslipidemia among PLHIV as compared to PWoH. Integration of strategies for the prevention and management of MetS disorders is needed in HIV treatment settings.

Cross-Reactivity of Two SARS-CoV-2 Serological Assays in a Setting Where Malaria Is Endemic.

Accurate SARS-CoV-2 serological assays are critical for COVID-19 serosurveillance. However, previous studies have indicated possible cross-reactivity of these assays, including in areas where malaria is endemic. We tested 213 well-characterized prepandemic samples from Nigeria using two SARS-CoV-2 serological assays, Abbott Architect IgG and Euroimmun NCP IgG assay, both targeting SARS-CoV-2 nucleocapsid protein. To assess antibody binding strength, an avidity assay was performed on these samples and on plasma from SARS-CoV-2 PCR-positive persons. Thirteen (6.1%) of 212 samples run on the Abbott assay and 38 (17.8%) of 213 run on the Euroimmun assay were positive. Anti-Plasmodium IgG levels were significantly higher among false positives for both Abbott and Euroimmun; no association was found with active Plasmodium falciparum infection. An avidity assay using various concentrations of urea wash in the Euroimmun assay reduced loosely bound IgG: of 37 positive/borderline prepandemic samples, 46%, 86%, 89%, and 97% became negative using 2 M, 4 M, 5 M, and 8 M urea washes, respectively. The wash slightly reduced avidity of antibodies from SARS-CoV-2 patients within 28 days of PCR confirmation; thereafter, avidity increased for all urea concentrations except 8 M. This validation found moderate to substantial cross-reactivity on two SARS-CoV-2 serological assays using samples from a setting where malaria is endemic. A simple urea wash appeared to alleviate issues of cross-reactivity.

HIV Coinfection Is Associated with Low-Fitness rpoB Variants in Rifampicin-Resistant Mycobacterium tuberculosis.

We analyzed 312 drug-resistant genomes of Mycobacterium tuberculosis isolates collected from HIV-coinfected and HIV-negative TB patients from nine countries with a high tuberculosis burden. We found that rifampicin-resistant M. tuberculosis strains isolated from HIV-coinfected patients carried disproportionally more resistance-conferring mutations in rpoB that are associated with a low fitness in the absence of the drug, suggesting these low-fitness rpoB variants can thrive in the context of reduced host immunity.

Predictors of first-line antiretroviral therapy failure among adults and adolescents living with HIV/AIDS in a large prevention and treatment program in Nigeria.

BACKGROUND: A substantial number of persons living with HIV (PLWH) in Nigeria do not experience durable viral suppression on first-line antiretroviral therapy (ART). Understanding risk factors for first-line treatment failure informs patient monitoring practices and distribution of limited resources for second-line regimens. We determined predictors of immunologic and virologic failures in a large ART delivery program in Abuja, Nigeria. METHODS: A retrospective cohort study was conducted at the University of Abuja Teaching Hospital, a tertiary health care facility, using data from February 2005 to December 2014 in Abuja, Nigeria. All PLWH aged ≥ 15 years who initiated ART with at least 6-month follow-up and one CD4 measurement were included. Immunologic failure was defined as a CD4 decrease to or below pre-ART level or persistent CD4 < 100 cells per mm3 after 6 months on ART. Virologic failure (VF) was defined as two consecutive HIV-1 RNA levels > 1000 copies/mL after at least 6 months of ART and enhanced adherence counselling. HIV drug resistance (Sanger sequences) was analyzed using the Stanford HIV database algorithm and scored for resistance to common nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Univariate and multivariate log binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Of 12,452 patients followed, a total of 5928 initiated ART with at least 6 months of follow-up and one CD4 measurement. The entry point for 3924 (66.2%) was through the program's own voluntary counseling and testing (VCT) center, while 1310 (22.1%) were referred from an outside clinic/program, 332 (5.6%) in-patients, and 373 (6.3%) through other entry points including prevention of mother to child transmission (PMTCT) and transferred from other programs. The mean CD4 at enrollment in care was 268 ± 23.7 cells per mm3, and the mean HIV-1 RNA was 3.3 ± 1.3.log10 copies/mL. A total of 3468 (80.5%) received nevirapine (NVP) and 2260 (19.5%) received efavirenz (EFV)-based regimens. A total of 2140 (36.1%) received tenofovir (TDF); 2662 (44.9%) zidovudine (AZT); and 1126 (19.0%) stavudine (d4T). Among those receiving TDF, 45.0% also received emtricitabine (FTC). In a multivariate model, immunologic failure was more common among PLWH with female gender as compared to male [RR (95% CI) 1.22 (1.07-1.40)] and less common among those who entered care at the program's VCT center as compared to other entry points [0.79 (0.64-0.91)], WHO stage 3/4 as compared to 1/2 [0.19 (0.16-0.22)], or CD4 200 + cells per mm3 as compared to lower [0.19 (0.16-0.22)]. Virologic failure was more common among PLWH who entered care at the program's VCT center as compared to other entry points [RR (95% CI) 1.45 (1.11-1.91) and those with CD4 < 200 cells per mm3 at entry into care as compared to higher [1.71 (1.36-2.16)]. Of 198 patient-derived samples sequenced during virologic failure, 42 (21%) were wild-type; 145 (73%) carried NNRTI drug resistance mutations; 151 (76.3%) M184I/V; 29 (14.6%) had ≥ 3 TAMs, and 37 (18.7%) had K65R, of whom all were on TDF-containing first-line regimens. CONCLUSIONS: In this cohort of Nigerian PLWH followed for a period of 9 years, immunologic criteria poorly predicted virologic failure. Furthermore, a subset of samples showed that patients failing ART for extended periods of time had HIV-1 strains harboring drug resistance mutations.

Cost of three models of care for drug-resistant tuberculosis patients in Nigeria.

BACKGROUND: Nigeria accounts for a significant proportion of the global drug-resistant tuberculosis (DR-TB) burden, a large proportion of which goes untreated. Different models for managing DR-TB treatment with varying levels of hospitalization are in use across Nigeria, however costing evidence is required to guide the scale up of DR-TB care. We aimed to estimate and compare the costs of different DR-TB treatment and care models in Nigeria. METHODS: We estimated the costs associated with three models of DR-TB treatment and care: Model (A) patients are hospitalized throughout the 8-month intensive phase, Model (B) patients are partially hospitalized during the intensive phase and Model (C) is entirely ambulatory. Costs of treatment, in-patient and outpatient care and diagnostic and monitoring tests were collected using a standardized data collection sheet from six sites through an ingredient's approach and cost models were based on the Nigerian National Tuberculosis, Leprosy and Buruli Ulcer Guideline - Sixth Edition (2014) and Guideline for programmatic and clinical management of drug-resistant tuberculosis in Nigeria (2015). RESULTS: Assuming adherence to the Nigerian DR-TB guidelines, the per patient cost of Model A was $18,528 USD, Model B $15,159 USD and Model C $9425 USD. Major drivers of cost included hospitalization (Models A and B) and costs of out-patient consultations and supervision (Model C). CONCLUSION: Utilizing a decentralized ambulatory model, is a more economically viable approach for the expansion of DR-TB care in Nigeria, given that patient beds for DR-TB treatment and care are limited and costs of hospitalized treatment are considerably more expensive than ambulatory models. Scale-up of less expensive ambulatory care models should be carefully considered in particular, when treatment efficacy is demonstrated to be similar across the different models to allow for patients not requiring hospitalization to be cared for in the least expensive way.

Performance and trend for quality of service in a large HIV/AIDS treatment program in Nigeria.

BACKGROUND: As antiretroviral therapy (ART) programs expand access, there is an increase in burden to a healthcare system. These results are reduced provider-patient contact time and poor programmatic and patient outcomes. Quality management offers providers a standardized approach for addressing the appropriateness of care to be applied in resource-limited settings. This study aimed to determine the trend of performance on HIV/AIDS quality management indicators of health facilities providing ART over a period of 5 years. METHODS: The annual performance scores of quality of care (QoC) indicators of 31 health facilities providing ART was extracted from a database covering a period of 5 years (from October 2008 to September 2012). The data are percentages that indicate scores of each health facility assessed based on compliance to National ART guidelines categorized into several indicator domains. A Chi square statistic for the trend, as well as test for departure from the trend line was determined. The p value associated with each indicator provides the significant level for testing an alternative hypothesis that the rate of change over the period considered for that indicator does not equal to zero. The slope of the regression line also gives the magnitude of the rate of change for each indicator by healthcare level across the review period. RESULTS: Generally, performance trends showed improvement across most indicator domains. The highest improvement occurred for "3 month loss to follow-up" and "1 year no-visit", with scores declining from 37 to 3%, and 42% to 12% respectively. However, there was a sharp decline in performance between 2010 and 2012 in weight monitoring of patients (p < 0.01), adherence assessment to ARVs (p < 0.01) and hematocrit measurements (p = 0.01). The aggregate rate of change ß, as obtained from the slope of the trend line is highly significant (p < 0.01) for all the quality of care indicators considered, whether improving or declining. CONCLUSION: Periodic assessment to determine HIV/AIDS quality of care can guide rapid scale-up of services to achieve universal coverage in resource-limited settings. Determining trends to understand patterns is very useful for improving programmatic and patient outcomes.

Cognitive Function Among Antiretroviral Treatment-Naive Individuals Infected With Human Immunodeficiency Virus Type 1 Subtype G Versus CRF02_AG in Nigeria.

Background: Human immunodeficiency virus type 1 (HIV-1) subtype has been shown to be associated with disease progression. We compared cognitive function between individuals infected with HIV-1 subtype G and CRF02_AG in Nigeria. Methods: For this cross-sectional study, samples were analyzed from 146 antiretroviral-naive participants. Genotypic analysis of plasma HIV RNA was performed by nested polymerase chain reaction of protease and reverse transcriptase genes, and sequences were aligned with curated HIV-1 subtype references. Cognitive status was determined using demographically adjusted T scores and global deficit score (GDS) obtained from a comprehensive neuropsychological test battery. Results: A total of 76 (52.1%) participants were infected with CRF02_AG, 48 (32.8%) with subtype G, and 22 (15.1%) with other HIV-1 strains. In a multivariable linear regression adjusting for plasma HIV RNA, CD4 count, and depression score, mean global T score was lower among subtype G-infected compared with CRF02_AG-infected participants (mean difference, -3.0 [95% confidence interval {CI}, -5.2, to -.7]; P = .011). Also, T scores were significantly lower among subtype G- than CRF02_AG-infected participants for the speed of information processing, executive function, and verbal fluency ability domains. Adjusting for similar variables in a logistic regression, the odds of global cognitive impairment (GDS ≥0.5) were 2.2 times higher among subtype G compared with CRF02_AG-infected participants (odds ratio, 2.2 [95% CI, .9-5.4]; P = .078). Conclusions: Cognitive performance was significantly worse among antiretroviral-naive individuals with HIV-1 subtype G vs CRF02_AG infection. Further studies are required to characterize the mechanistic basis for these differences.

Plasma HIV RNA level is associated with neurocognitive function among HIV-1-infected patients in Nigeria.

Plasma HIV RNA level has been shown to correlate with HIV disease progression, morbidity, and mortality. We examined the association between levels of plasma HIV RNA and cognitive function among patients in Nigeria. A total of 179 HIV-1-infected participants with available plasma HIV RNA results and followed longitudinally for up to 2 years were included in this study. Blood samples from participants were used for the measurement of plasma HIV RNA and CD4+ T cell count. Utilizing demographic and practice effect-adjusted T scores obtained from a seven-domain neuropsychological test battery, cognitive status was determined by the global deficit score (GDS) approach, with a GDS ≥ 0.5 indicating cognitive impairment. In a longitudinal multivariable linear regression analysis, adjusting for CD4 cell count, Beck's Depression Score, age, gender, years of education, and antiretroviral treatment status, global T scores decreased by 0.35 per log10 increase in plasma HIV RNA [p = 0.033]. Adjusting for the same variables in a multivariable logistic regression, the odds of neurocognitive impairment were 28% higher per log10 increase in plasma HIV RNA (OR 1.28 [95% CI 1.08, 1.51]; p = 0.005). There were statistically significant associations for the speed of information processing, executive, and verbal fluency domains in both linear and logistic regression analyses. We found a significant association between plasma HIV RNA levels and cognitive function in both baseline (cross-sectional) and longitudinal analyses. However, the latter was significantly attenuated due to weak association among antiretroviral-treated individuals.

Peripheral blood lymphocyte HIV DNA levels correlate with HIV associated neurocognitive disorders in Nigeria.

Mononuclear cells play key roles in the pathogenic mechanisms leading to HIV-associated neurocognitive disorders (HANDs). We examined the association between HIV DNA within peripheral blood mononuclear cell (PBMC) subsets and HAND in Nigeria. PBMCs were collected at baseline from 36 antiretroviral naive participants. CD14+ cells and T&B lymphocyte fractions were isolated by, respectively, positive and negative magnetic bead separation. Total HIV DNA within CD14+ and T&B cells were separately quantified using real-time PCR assay targeting HIV LTR-gag and cell input numbers determined by CCR5 copies/sample. Utilizing demographically adjusted T scores obtained from a 7-domain neuropsychological test battery, cognitive status was determined by the global deficit score (GDS) approach, with a GDS of ≥0.5 indicating cognitive impairment. In a linear regression adjusting for plasma HIV RNA, CD4 and lymphocyte count, Beck's depression score, and years of education, there was 0.04 lower log10 HIV DNA copies within T&B lymphocytes per unit increase in global T score (p = 0.02). Adjusting for the same variables in a logistic regression, the odds of cognitive impairment were 6.2 times greater per log10 increase in HIV DNA within T&B lymphocytes (p = 0.048). The association between cognitive impairment and HIV DNA within CD14+ monocytes did not reach statistical significance. In this pretreatment cohort with mild cognitive dysfunction, we found a strong association between levels of HIV DNA within the lymphocyte subset and HAND independent of plasma HIV RNA. These findings likely reflect the neurologic impact of a larger HIV reservoir and active viral replication.

Barriers to and Facilitators of Adherence to Exclusive Breastfeeding Practices Among HIV Infected and Non-Infected Women in Jos, Nigeria.

Objectives In Nigeria adherence to exclusive breastfeeding (EBF) practices is currently suboptimal and a better understanding of the factors affecting adherence to EBF is needed. We sought to identify and delineate the barriers to and facilitators of adherence to EBF amongst HIV-infected and uninfected women in Nigeria. Methods We explored the barriers and facilitators to EBF amongst 37 (25 HIV-infected and 12 HIV-uninfected) pregnant women attending an antenatal clinic in Jos, Nigeria. In-depth interviews were conducted with each of the pregnant women in their third trimester of pregnancy and again 1 month after giving birth. Results The themes that emerged were mothers' feeding intentions, significant role players in the decision to breastfeed, perceived barriers (e.g. physiological issues, stigma, employment) and perceived facilitators (e.g. pleasure and enjoyment derived from breastfeeding, natural milk from God, disclosure and family support) associated with EBF. Conclusions Most women preferred EBF and offered it to their infants. However, more efforts are needed to improve support structures at home and at work to accommodate women who choose to do EBF.

Laboratory Innovation Towards Quality Program Sustainability.

Laboratory innovation significantly affects program sustainability of HIV programs in low and middle income countries (LMICs) far beyond its immediate sphere of impact. Innovation in rapid development of diagnostic technologies, improved quality management systems, strengthened laboratory management, affordable external quality assurance and accreditation schemes, and building local capacity have reduced costs, brought quality improvement to point-of-care testing, increased access to testing services, reduced treatment and prevention costs and opened the door to the real possibility of ending the AIDS epidemic. However, for effectively implemented laboratory innovation to contribute to HIV quality program sustainability, it must be implemented within the overall context of the national strategic plan and HIV treatment programs. The high quality of HIV rapid diagnostic test was a breakthrough that made it possible for more persons to learn their HIV status, receive counseling, and if infected to receive treatment. Likewise, the use of dried blood spots made the shipment of samples easier for the assessment of different variables of HIV infection-molecular diagnosis, CD4+ cell counts, HIV antibodies, drug resistance surveillance, and even antiretroviral drug level measurements. Such advancement is critical for to reaching the UNAIDS target of 90-90-90 and for bringing the AIDS epidemic to an end, especially in LMICs.

Development of a prospective cohort of HIV Exposed Sero-Negative (HESN) individuals in Jos Nigeria.

BACKGROUND: HIV/AIDS continues to be a global health problem. With currently no cure, it is critical to get an effective vaccine to add to the arsenal of prevention and treatment tools. HIV Exposed Sero-Negative (HESN) individuals were enrolled and followed for 2 years. METHODS: A prospective observational cohort study to enroll HESN volunteers and their partners was developed with a 2-year follow up. This was a vaccine preparedness study and designed as a Phase IIb trial. We provided counseling, lab testing and conducted medical examinations for all enrollees. RESULTS: A total of 534 HESN were enrolled with 48 % (256) females and 52 % (278) males, a mean age of 37 ± 9 years. Three female HESN enrollees seroconverted giving this cohort a HIV incidence rate [95 % coefficient interval (CI)] of 3.2 (2.3-4.2) per 100,000 person-months of observation. Baseline analysis showed that female HESN are 24 % more likely to have their spouse consistently use condoms (RR 1.24; p = 0.04); 16 % more likely to have HIV+ partners with detectable viral load (RR 1.16, p = 0.03) and 28 % more likely that their HIV+ partners has a CD4 count less than 350cells/µl (RR 1.28, p = 0.03) when compared to male HESN. CONCLUSIONS: Our findings suggest that female HESN are more at risk of HIV acquisition due the low CD4 counts and detectable viral load among their HIV+ spouses. Moreover, we provide additional information on incidence and risk factors among naturally exposed persons, which might impact biomedical prevention research and immune responses to HIV vaccines.

Cost-effectiveness of point-of-care digital chest-x-ray in HIV patients with pulmonary mycobacterial infections in Nigeria.

BACKGROUND: Chest-x-ray is routinely used in the diagnosis of smear negative tuberculosis (TB). This study assesses the incremental cost per true positive test of a point-of-care digital chest-x-ray, in the diagnosis of pulmonary mycobacterial infections among HIV patients with presumed tuberculosis undetected by smear microscopy. METHODS: Consecutive patients with clinical suspicion of pulmonary tuberculosis were serially tested for Human immunodeficiency virus (HIV), their sputum examined for Acid Fast Bacilli then cultured in broth and solid media. Cultures characterized as tuberculous (M.tb) and non-tuberculous (NTM) mycobacteria by Hain assays were used as gold standards. A chest-x-ray was classified as: (1) consistent for TB, (2) not consistent for TB and (3) no pathology. RESULTS: Of the 1391 suspected cases enrolled, complete data were available for 952 (68%): 753/952 (79%) had negative smear tests while 150/753 (20%) had cultures positive for TB. Of those, 82/150 (55%) had chest-x-ray signs consistent with TB and 29/82 (35%) were positive for HIV. Within the co-infected, 9/29 (31%) had NTM infections. Among all suspects, the cost per positive case detected using smear microscopy test was $52.84; the overall incremental cost per positive case using chest-x-ray in smear negatives was $23.42, and in smear negative, HIV positive patients the cost was $15.77. CONCLUSION: Point-of-care chest-x-ray is a cost-effective diagnostic tool for smear negative HIV positive patients with pulmonary mycobacterial infection.

Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses.

Infants who are exposed to HIV but uninfected (iHEU) have higher risk of infectious morbidity than infants who are HIV-unexposed and uninfected (iHUU), possibly due to altered immunity. As infant gut microbiota may influence immune development, we evaluated the effects of HIV exposure on infant gut microbiota and its association with tetanus toxoid vaccine responses. We evaluated the gut microbiota of 82 South African (61 iHEU and 21 iHUU) and 196 Nigerian (141 iHEU and 55 iHUU) infants at <1 and 15 weeks of life by 16S rRNA gene sequencing. Anti-tetanus antibodies were measured by enzyme-linked immunosorbent assay at matched time points. Gut microbiota in the 278 included infants and its succession were more strongly influenced by geographical location and age than by HIV exposure. Microbiota of Nigerian infants, who were exclusively breastfed, drastically changed over 15 weeks, becoming dominated by Bifidobacterium longum subspecies infantis. This change was not observed among South African infants, even when limiting the analysis to exclusively breastfed infants. The Least Absolute Shrinkage and Selection Operator regression suggested that HIV exposure and gut microbiota were independently associated with tetanus titers at week 15, and that high passively transferred antibody levels, as seen in the Nigerian cohort, may mitigate these effects. In conclusion, in two African cohorts, HIV exposure minimally altered the infant gut microbiota compared to age and setting, but both specific gut microbes and HIV exposure independently predicted humoral tetanus vaccine responses.IMPORTANCEGut microbiota plays an essential role in immune system development. Since infants HIV-exposed and uninfected (iHEU) are more vulnerable to infectious diseases than unexposed infants, we explored the impact of HIV exposure on gut microbiota and its association with vaccine responses. This study was conducted in two African countries with rapidly increasing numbers of iHEU. Infant HIV exposure did not substantially affect gut microbial succession, but geographic location had a strong effect. However, both the relative abundance of specific gut microbes and HIV exposure were independently associated with tetanus titers, which were also influenced by baseline tetanus titers (maternal transfer). Our findings provide insight into the effect of HIV exposure, passive maternal antibody, and gut microbiota on infant humoral vaccine responses.