Differential effects of sex in a West African cohort of HIV-1, HIV-2 and HIV-1/2 dually infected patients: men are worse off.

OBJECTIVES: Several studies have reported conflicting effects of sex on HIV-1 infection. We describe differences in baseline characteristics and assess the impact of sex on HIV progression among patients at a clinic with many HIV-2 and HIV-1/2 dually infected patients. METHODS: This study utilised a retrospective cohort of treatment-naïve adults at the largest HIV clinic in Guinea-Bissau from 6 June 2005 to 1 December 2013. Baseline characteristics were assessed and the patients followed until death, transfer, loss to follow-up, or 1 June 2014. We estimated the time from the first clinic visit until initiation of ART, death or loss to follow-up using Cox proportional hazard models. RESULTS: A total of 5694 patients were included in the study, 3702 women (65%) and 1992 men (35%). Women were more likely than men to be infected with HIV-2 (19% vs. 15%, P < 0.01) or dually infected with HIV-1/2 (11% vs. 9%, P = 0.02). For all HIV types, women were younger (median 35 vs. 40 years), less likely to have schooling (55% vs. 77%) or to be married (46% vs. 67%), and had higher baseline CD4 cell counts (median 214 vs. 178 cells/µl). Men had a higher age-adjusted mortality rate (hazard rate ratio (HRR) 1.29, 95% confidence interval (CI) 1.09-1.52) and were more often lost to follow-up (HRR 1.27, 95% CI 1.17-1.39). CONCLUSION: Significant differences exist between HIV-infected men and women regardless of HIV type. Men seek treatment at a later stage and, despite better socio-economic status, have higher mortality and loss to follow-up than women.

A clinical score has utility in tuberculosis case-finding among patients with HIV: A feasibility study from Bissau.

BACKGROUND: Clinical scores are promising case-finding tools for tuberculosis (TB) among HIV-infected patients. The Bandim TBscore has been shown to increase the diagnostic yield among patients with presumed TB in general, but has not previously been tested among newly diagnosed HIV patients at high risk of TB. METHODS: HIV-infected patients were included in this cross-sectional study. A pre-post-intervention study design was used to assess the outcome of a change in practice, i.e. the application of a clinical score (TBscore) consisting of 13 signs and symptoms to assess the need for further TB diagnostics. Patients with a TBscore ≥2 were evaluated using smear microscopy and Xpert MTB/RIF. A TB diagnosis was made based on microbiology or clinical evaluation. The sensitivity and specificity of the TBscore were compared with those of World Health Organization symptoms. RESULTS: The TB prevalence among newly enrolled HIV-infected patients during the study period was 13.4% (22/164). Using the TBscore and a diagnostic algorithm, it was possible to increase the proportion of patients started on TB treatment from 2.7% (10/367) the year before the study to 10.4% (17/164) during the study period. Five patients diagnosed with TB were not started on TB treatment as they were lost to follow-up or died. With a cut-off value of 2, the TBscore had a sensitivity, specificity, positive predictive value, and negative predictive value of 95.5% (21/22), 36.9% (41/111), 23.1% (22/118), and 97.6% (41/42), respectively. CONCLUSION: The TBscore is useful for standardized TB screening among HIV-infected individuals and may be a valuable tool to prioritize patients at high risk of TB.

Protease Inhibitors or NNRTIs as First-Line HIV-1 Treatment in West Africa (PIONA): A Randomized Controlled Trial.

BACKGROUND: Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are recommended as part of first-line treatment for HIV-1 in Africa. However, NNRTI-based regimens are more prone to resistance development than protease inhibitors (PIs) in a context in which drug interruptions are frequent. The aim of this study was to compare the efficacy and tolerability of NNRTIs with PIs in HIV-1-infected patients in Guinea-Bissau. METHODS: This open-label randomized, 2-arm superiority trial compared the use of 2 NRTIs plus either one NNRTI (efavirenz or nevirapine) or one PI (lopinavir/ritonavir) in treatment-naive HIV-1-infected adults in the Bissau HIV Cohort (ClinicalTrials.gov, NCT0019235). The primary endpoint was HIV-1 RNA <400 copies per milliliter after 12 months of treatment. RESULTS: Between May 5, 2011, and April 26, 2013, 400 patients were included in the study. In an intention-to-treat analysis, the proportions of patients with viral suppression were similar in the NNRTI [65/197 (33.0%)] and PI [68/203 (33.5%)] arms (P = 0.92). No PI resistance was detected, but high-level NNRTI resistance was seen in 17/30 (56.7%) of NNRTI vs. 3/26 (11.5%) of PI-treated patients, P < 0.01. After 1 year of follow-up, 65 patients died (16.3%) and 93 were lost to follow-up (23.3%). There was no difference in mortality (hazard ratio 0.84, 95% confidence interval: 0.51 to 1.36) or frequency of clinical adverse events between treatment arms [NNRTI: 73/197 (37.1%); and PI: 69/203 (34.0%); P = 0.52]. CONCLUSIONS: In patients at an HIV clinic in Guinea-Bissau, treatment with PIs led to less development of resistance compared with NNRTIs but was not superior in terms of viral suppression, CD4 cell increment, mortality, or severe adverse events.

The influence of human leukocyte antigen-types on disease progression among HIV-2 infected patients in Guinea-Bissau.

OBJECTIVES: HIV-2 is endemic in West Africa and is characterized by lower transmissibility because of lower viral load, and HIV-2-infected persons usually have a slower progression to AIDS. The mechanisms behind the slower disease progression are unknown. The main objective was to identify specific HLA class I and II alleles that may influence the disease progression of HIV-2 infection. DESIGN: Cohort follow-up study. METHODS: We used high-resolution HLA typing of DNA from 437 antiretroviral naive HIV-2-infected patients from the Bissau HIV Cohort, Guinea-Bissau, to identify HLA alleles with an influence on HIV-2 disease progression. The effect of HLA-type on viral load and CD4 cell count was assessed initially by ranksum-test and t-test, followed by adjusted logistic regression and multivariable linear regression analysis, respectively. RESULTS: Three alleles (HLA-B58:01, HLA-DPB110:01 and HLA-DRB111:01) were associated with lower possibility of detectable baseline plasma viral load (P = 0.002, P = 0.044 and P = 0.033, respectively), and no alleles were associated with higher possibility of detectable plasma viral load. HLA-DPB110:01 and HLA-DRB111:01 were in linkage disequilibrium (P = 0.047). Patients with heterozygous HLA types in all their HLA class I loci or in one or two loci were not more likely to have undetectable viral load compared with patients that were homozygous in all their class I loci after adjusting for sex and CD4 cell count (P = 0.93 and P = 0.88, respectively). CONCLUSION: The three alleles HLA-B58:01, HLA-DPB110:01 and HLA-DRB111:01 may protect against HIV-2 disease progression towards AIDS.

Increased mortality among HIV infected patients with cryptococcal antigenemia in Guinea-Bissau.

Cryptococcal antigenemia may precede development of cryptococcal meningitis and death among patients with advanced HIV infection. Among 200 retrospectively and randomly selected ART-naïve patients with CD4 counts < 100 cells/µl from Guinea-Bissau, 20 (10%) had a positive cryptococcal antigen test. Self-reported headache and fever were predictors of a positive test, while cryptococcal antigenemia was a strong predictor of death within the first year of follow-up, MRR 2.22 (95% CI: 1.15-4.30). Screening for cryptococcal antigenemia should be implemented for patients with advanced HIV in Guinea-Bissau. Pre-emptive anti-fungal therapy should be initiated prior to ART-initiation if the screening is positive.

Clinical presentation and opportunistic infections in HIV-1, HIV-2 and HIV-1/2 dual seropositive patients in Guinea-Bissau.

BACKGROUND: Better understanding of HIV-2 infection is likely to affect the patient care in areas where HIV-2 is prevalent. In this study, we aimed to characterize the clinical presentations among HIV-1, HIV-2 and HIV-1/2 dual seropositive patients. METHODS: In a cross-sectional study, newly diagnosed HIV patients attending the HIV outpatient clinic at Hospital Nacional Simão Mendes in Guinea-Bissau were enrolled. Demographical and clinical data were collected and compared between HIV-1, HIV-2 and HIV-1/2 dual seropositive patients. RESULTS: A total of 169 patients (76% HIV-1, 17% HIV-2 and 6% HIV 1/2) were included in the study between 21 March 2012 and 14 December 2012. HIV-1 seropositive patients were younger than HIV-2 and HIV-1/2 seropositive patients, but no difference in sex was observed. Patients with HIV-1 and HIV-1/2 had a lower baseline CD4 cell count than HIV-2 seropositive patients (median CD4 cell count 185, 198 and 404 cells/µl, respectively (p value 0.001 and 0.05). HIV-1 seropositive patients had a lower BMI and a higher prevalence of weight loss, skin rash and productive cough than HIV-2 seropositive patients (p value 0.03, 0.002, 0.03 and 0.04). Only four cases (2%) of pulmonary tuberculosis (TB) were diagnosed. One patient (1/96, 1%) was tested positive for cryptococcal antigen. CONCLUSION: HIV-1 and HIV-1/2 seropositive patients have lower CD4 cell counts than HIV-2 seropositive patients when diagnosed with HIV with only minor clinical and demographic differences among groups. Few patients were diagnosed with TB and cryptococcal disease was not found to be a major opportunistic infection among newly diagnosed HIV patients.

Lack of awareness of treatment failure among HIV-1-infected patients in Guinea-Bissau - a retrospective cohort study.

INTRODUCTION: With more people receiving antiretroviral treatment (ART), the need to detect treatment failure and switch to second-line ART has also increased. We assessed CD4 cell counts (as a marker of treatment failure), determined the rate of switching to second-line treatment and evaluated mortality related to treatment failure among HIV-infected patients in Guinea-Bissau. METHODS: In this retrospective cohort study, adult patients infected with HIV-1 receiving ≥6 months of ART at an HIV clinic in Bissau were included from June 2005 to July 2014 and followed until January 2015. Treatment failure was defined as 1) a fall in CD4 count to baseline (or below) or 2) CD4 levels persistently below 100 cells/µL after ≥6 months of ART. Cox hazard models, with time since six months of ART as the time-varying coefficient, were used to estimate the hazard ratio for death and loss to follow-up. RESULTS: We assessed 1,591 HIV-1-infected patients for immunological treatment failure. Treatment failure could not be determined in 594 patients (37.3%) because of missing CD4 cell counts. Among the remaining 997 patients, 393 (39.4%) experienced failure. Only 39 patients (9.9%) with failure were switched from first- to second-line ART. The overall switching rate was 3.1 per 100 person-years. Mortality rate was higher in patients with than without treatment failure, with adjusted hazard rate ratios (HRRs) 10.0 (95% CI: 0.9-107.8), 7.6 (95% CI: 1.6-35.5) and 3.1 (95% CI: 1.5-6.3) in the first, second and following years, respectively. During the first year of follow-up, patients experiencing treatment failure had a higher risk of being lost to follow-up than patients not experiencing treatment failure (adjusted HRR 4.4; 95% CI: 1.7-11.8). CONCLUSIONS: We found a high rate of treatment failure, an alarmingly high number of patients for whom treatment failure could not be assessed, and a low rate of switching to a second-line therapy. These factors could lead to an increased risk of resistance development and excess mortality.

Cohort Profile: The Bissau HIV Cohort-a cohort of HIV-1, HIV-2 and co-infected patients.

The West African country Guinea-Bissau is home to the world's highest prevalence of HIV-2, and its HIV-1 prevalence is rising. Other chronic viral infections like human T-lymphotropic virus type 1 (HTLV-1) and hepatitis B virus are common as well. The Bissau HIV Cohort was started in 2007 to gain new insights into the overall effect of introducing antiretroviral treatment in a treatment-naïve population with concomitant infection with three retroviruses (HIV-1, HIV-2 and HTLV-1) and tuberculosis. The cohort includes patients from the HIV clinic at Hospital Nacional Simão Mendes, the main hospital in Bissau, the capital of the country. From July 2007 to June 2013, 3762 HIV-infected patients (69% HIV-1, 18% HIV-2, 11% HIV-1/2 and 2% HIV type unknown) were included in the world's largest single-centre HIV-2 cohort. Demographic and clinical data are collected at baseline and every 6 months, together with CD4 cell count and routine biochemistry analyses. Plasma and cells are stored in a biobank in Denmark. The Bissau HIV Cohort is administered by the Bissau HIV Cohort study group. Potential collaborators are invited to contact the chair of the cohort study group, Christian Wejse, e-mail: [wejse@dadlnet.dk].