TB screening, prevention and treatment cascade in a Malawi prison.

BACKGROUND Incarcerated individuals, especially in high HIV and TB burden settings, are at increased risk of latent TB infection and/or TB disease. We implemented a comprehensive HIV-TB intervention in a Malawi prison and studied its feasibility.METHODS Between February and December 2019, consenting individuals underwent screening for HIV, TB infection and TB disease. HIV-positive individuals without TB disease were treated with a fixed-dose combination of isoniazid, cotrimoxazole and vitamin B6 (INH-CTX-B6). HIV-negative persons with TB infection received 12 weeks of isoniazid and rifapentine (3HP).RESULTS Of 1,546 consenting individuals, 1,498 (96.9%) were screened and 1,427 (92.3%) included in the analysis: 96.4% were male, the median age was 31 years (IQR 25-38). Twenty-nine (2.1%) participants were diagnosed with TB disease, of whom 89.7% started and 61.5% completed TB treatment. Of the 1,427 included, 341 (23.9%) were HIV-positive, of whom 98.5% on antiretroviral therapy and 95% were started on INH-CTX-B6. Among 1,086 HIV-negative participants, 1,015 (93.5%) underwent the tuberculin skin test (TST), 670 (65.9%) were TST-positive, 666 (99.4%) started 3HP and 570 (85.5%) completed 3HP treatment.CONCLUSION A comprehensive TB screening and treatment package among incarcerated individuals was acceptable and feasible, and showed high prevalence of HIV, TB disease and TB infection. Treatment uptake was excellent, but treatment completion needs to be improved. Greater investment in comprehensive HIV-TB services, including access to shorter TB regimens and follow-up upon release, is needed for incarcerated individuals.

High level of HIV drug resistance informs dolutegravir roll-out and optimized NRTI backbone strategy in Mozambique.

BACKGROUND: HIV drug resistance (HIV-DR) is rising in sub-Saharan Africa in both ART-naive and ART-experienced patients. OBJECTIVES: To estimate the level of acquired DR (ADR) and pre-treatment DR (PDR) across selected urban and rural sites in Southern Africa, in Mozambique. METHODS: We conducted two cross-sectional surveys among adult HIV patients (October 2017-18) assessing ADR and PDR. In the (ADR) survey, those on NNRTI-based first-line ART for ≥6 months were recruited (three sites). In the PDR survey, those ART-naive or experienced with ≥3 months of treatment interruption prior were enrolled (eight sites). RESULTS: Among 1113 ADR survey participants 83% were receiving tenofovir (TDF)/lamivudine (3TC)/efavirenz (EFV). The median time on ART was 4.5 years (Maputo) and 3.2 years (Tete), 8.3% (95% CI 6.2%-10.6%, Maputo) and 15.5% (Tete) had a VL ≥ 1000 copies/mL, among whom 66% and 76.4% had NNRTI+NRTI resistance, and 52.8% and 66.7% had 3TC+TDF-DR. Among those on TDF regimens, 31.1% (Maputo) and 42.2% (Tete) were still TDF susceptible, whereas 24.4% and 11.5% had TDF+zidovudine (ZDV)-DR. Among those on ZDV regimens, 25% and 54.5% had TDF+ZDV-DR. The PDR survey included 735 participants: NNRTI-PDR was 16.8% (12.0-22.6) (Maputo) and 31.2% (26.2-36.6) (Tete), with a higher proportion (≥50%) among those previously on ART affected by PDR. CONCLUSIONS: In Mozambique, viral failure was driven by NNRTI and NRTI resistance, with NRTI DR affecting backbone options. NNRTI-PDR levels surpassed the WHO 10% 'alert' threshold. Replacing NNRTI first-line drugs is urgent, as is frequent viral load monitoring and resistance surveillance. Changing NRTI backbones when switching to second-line regimens may need reconsideration.

The HIV cascade of care among serodiscordant couples in four high HIV prevalence settings in sub-Saharan Africa.

BACKGROUND:  HIV-serodiscordant couples are at high risk of HIV transmission. In sub-Saharan Africa, HIV-serodiscordant couples contribute ~30% of all new infections in the region. OBJECTIVES: To quantify the prevalence of HIV-serodiscordant couples and evaluate steps of the HIV cascade of care among people living with HIV in serodiscordant relationships in four high-prevalence settings in sub-Saharan Africa. METHODS:  Four HIV prevalence surveys were conducted: in Ndhiwa (Kenya) in 2012, in Chiradzulu (Malawi) in 2013, and in Gutu (Zimbabwe) and Nsanje (Malawi) in 2016. Eligible individuals aged 15 - 59 years were asked to participate in voluntary rapid HIV testing. Viral load and CD4 counts were measured on those who tested HIV-positive. A couple was defined as a man and a woman who reported being married or cohabiting and were living together in the same household. RESULTS: Among 4 385 couples, the prevalence of HIV serodiscordancy was 10.9% (95% confidence interval (CI) 10.2 - 11.5) overall, ranging from 6.7% (95% CI 5.6 - 7.9) in Nsanje to 15.8% (95% CI 14.5 - 17.3) in Ndhiwa. Men were the HIV-positive partner in 62.7% of the serodiscordant couples in Ndhiwa, in 60.4% in Gutu, in 48.8% in Chiradzulu and in 50.9% in Nsanje. Status awareness among HIV-positive partners in serodiscordant couples ranged from 45.4% in Ndhiwa to 70.7% in Gutu. Viral load suppression (VLS) ranged from 33.9% in Ndhiwa to 68.5% in Nsanje. VLS was similar by sex in three settings, Ndhiwa (37.8% (men) v. 27.8% (women); p=0.16), Nsanje (60.7% v. 76.9%; p=0.21) and Gutu (48.2% v. 55.6%; p=0.63), and dissimilar by sex in Chiradzulu (44.4% v. 62.7%; p=0.03). CONCLUSIONS: Low HIV status awareness and poor VLS among HIV-positive partners are major gaps in preventing transmission among serodiscordant couples. Intensifying programmes that target couples to test for HIV and timely antiretroviral therapy initiation could increase VLS and reduce HIV transmission.

Impact of acute malaria on plasma concentrations of transferrin receptors.

The acute-phase response to infection alters the plasma concentrations of most biochemical measures of iron status, rendering assessment of status difficult. Soluble transferrin receptors (TfR) may be an exception but have not been examined longitudinally during the major metabolic and inflammatory changes which occur during clinical malaria. Blood samples were collected daily during hospitalization, and again at a follow-up 2-6 weeks after discharge, from adult, mainly European, patients (n = 49) who developed uncomplicated Plasmodium falciparum malaria following visits to endemic areas. Parasitaemia and plasma concentrations of ferritin, TfR, C-reactive protein (CRP), alpha 1-acid glycoprotein (AGP) and alpha 1-antichymotrypsin (ACT) were measured. The concentrations of CRP, AGP and ACT correlated highly (P < 0.001) with each other and with plasma ferritin, and were significantly higher (P < 0.05) at all time points in hospital compared to the follow-up. TfR concentration correlated negatively and significantly (P < 0.05) with AGP and CRP but not with ACT or ferritin, and was significantly lower (around 30%) at all time points in hospital compared to follow-up, although in only 1 subject did it ever fall outside the normal reference range. In areas where both iron deficiency and clinical episodes of malaria are common, plasma TfR values need to be interpreted cautiously as indicators of iron status.