Same-day antiretroviral therapy initiation in people living with HIV who have tuberculosis symptoms: a systematic review

Objectives Tuberculosis symptoms are very common among people living with HIV (PLHIV) initiating antiretroviral therapy (ART), are not specific for tuberculosis disease and may result in delayed ART start. The risks and benefits of same-day ART initiation in PLHIV with tuberculosis symptoms are unknown. Methods We systematically reviewed nine databases on 12 March 2020 to identify studies that investigated same-day ART initiation among PLHIV with tuberculosis symptoms and reported both their approach to TB screening and clinical outcomes. We extracted and summarised data about TB screening, numbers of people starting same-day ART and outcomes. Results We included four studies. Two studies deferred ART for everyone with any tuberculosis symptoms (one or more of cough, fever, night sweats or weight loss) and substantial numbers of people had deferred ART start (28% and 39% did not start same-day ART). Two studies permitted some people with tuberculosis symptoms to start same-day ART, and fewer people deferred ART (2% and 16% did not start same-day). Two of the four studies were conducted sequentially; proven viral load suppression at eight months was 31% when everyone with tuberculosis symptoms had ART deferred, and 44% when algorithm was changed so that some people with tuberculosis symptoms could start same-day ART. Conclusions Although tuberculosissymptoms are very common in people starting ART, there is insufficient evidence about whether presence of tuberculosis symptoms should lead to ART start being deferred or not. Research to inform clear guidelines would help maximise benefits of sameday ART

Optimizing HIV testing services in sub-Saharan Africa: cost and performance of verification testing with HIV self-tests and tests for triage

INTRODUCTION: Strategies employing a single rapid diagnostic test (RDT) such as HIV self-testing (HIVST) or "test for triage" (T4T) are proposed to increase HIV testing programme impact. Current guidelines recommend serial testing with two or three RDTs for HIV diagnosis, followed by retesting with the same algorithm to verify HIV-positive status before anti-retroviral therapy (ART) initiation. We investigated whether clients presenting to HIV testing services (HTS) following a single reactive RDT must undergo the diagnostic algorithm twice to diagnose and verify HIV-positive status, or whether a diagnosis with the setting-specific algorithm is adequate for ART initiation. METHODS: We calculated (1) expected number of false-positive (FP) misclassifications per 10,000 HIV negative persons tested, (2) positive predictive value (PPV) of the overall HIV testing strategy compared to the WHO recommended PPV ≥99%, and (3) expected cost per FP misclassified person identified by additional verification testing in a typical low-/middle-income setting, compared to the expected lifetime ART cost of $3000. Scenarios considered were as follows: 10$5879, $3770, and$24,259 respectively. Results were sensitive to assumptions about accuracy of self-reported reactive results and whether reactive triage test results influenced biased interpretation of subsequent RDT results by the HTS provider. CONCLUSIONS: Diagnosis with the full algorithm following presentation with a reactive triage test is expected to achieve PPV above the 99% threshold. Continuing verification testing prior to ART initiation remains recommended, but HIV testing strategies involving HIVST and T4T may provide opportunities to maintain quality while increasing efficiency as part of broader restructuring of HIV testing service delivery

HIV self-testing alone or with additional interventions, including financial incentives, and linkage to care or prevention among male partners of antenatal care clinic attendees in Malawi: An adaptive multi-arm, multi-stage cluster randomised trial

Background Conventional HIV testing services have been less comprehensive in reaching men than in reaching women globally, but HIV self-testing (HIVST) appears to be an acceptable alternative. Measurement of linkage to post-test services following HIVST remains the biggest challenge, yet is the biggest driver of cost-effectiveness. We investigated the impact of HIVST alone or with additional interventions on the uptake of testing and linkage to care or prevention among male partners of antenatal care clinic attendees in a novel adaptive trial. Methods and findings An adaptive multi-arm, 2-stage cluster randomised trial was conducted between 8 August 2016 and 30 June 2017, with antenatal care clinic (ANC) days (i.e., clusters of women attending on a single day) as the unit of randomisation. Recruitment was from Ndirande, Bangwe, and Zingwangwa primary health clinics in urban Blantyre, Malawi. Women attending an ANC for the first time for their current pregnancy (regardless of trimester), 18 years and older, with a primary male partner not known to be on ART were enrolled in the trial after giving consent. Randomisation was to either the standard of care (SOC; with a clinic invitation letter to the male partner) or 1 of 5 intervention arms: the first arm provided women with 2 HIVST kits for their partners; the second and third arms provided 2 HIVST kits along with a conditional fixed financial incentive of $3 or$10; the fourth arm provided 2 HIVST kits and a 10% chance of receiving $30 in a lottery; and the fifth arm provided 2 HIVST kits and a phone call reminder for the women’s partners. The primary outcome was the proportion of male partners who were reported to have tested for HIV and linked into care or prevention within 28 days, with referral for antiretroviral therapy (ART) or circumcision accordingly. Women were interviewed at 28 days about partner testing and adverse events. Cluster-level summaries compared each intervention versus SOC using eligible women as the denominator (intention-to-treat). Risk ratios were adjusted for male partner testing history and recruitment clinic. A total of 2,349/3,137 (74.9$3 (geometric mean 40.9%, adjusted risk ratio [aRR] 3.01 [95% CI 1.63–5.57], p < 0.001), HIVST + $10 (51.7$23.73 and $28.08 for the HIVST +$3 and HIVST + $10 arms, respectively. Notable limitations of the trial included the relatively small number of clusters randomised to each arm, proxy reporting of the male partner testing outcome, and being unable to evaluate retention in care. Conclusions In this study, the odds of men’s linkage to care or prevention increased substantially using conditional fixed financial incentives plus partner-delivered HIVST; combinations were potentially affordable

Prevalence of nonsuppressed viral load and associated factors among HIV-positive adults receiving antiretroviral therapy in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017): results from population-based nationally representative surveys.

INTRODUCTION The global target for 2020 is that ≥90% of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) will achieve viral load suppression (VLS). We examined VLS and its determinants among adults receiving ART for at least four months. METHODS We analysed data from the population-based HIV impact assessment (PHIA) surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017). PHIA surveys are nationally representative, cross-sectional household surveys. Data collection included structured interviews, home-based HIV testing and laboratory testing. Blood samples from PLHIV were analysed for HIV RNA, CD4 counts and recent exposure to antiretroviral drugs (ARVs). We calculated representative estimates for the prevalence of VLS (viral load <1000 copies/mL), nonsuppressed viral load (NVL; viral load ≥1000 copies/mL), virologic failure (VF; ARVs present and viral load ≥1000 copies/mL), interrupted ART (ARVs absent and viral load ≥1000 copies/mL) and rates of switching to second-line ART (protease inhibitors present) among PLHIV aged 15 to 59 years who participated in the PHIA surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe, initiated ART at least four months before the survey and were receiving ART at the time of the survey (according to self-report or ARV testing). We calculated odds ratios and incidence rate ratios for factors associated with NVL, VF, interrupted ART, and switching to second-line ART. RESULTS We included 9200 adults receiving ART of whom 88.8% had VLS and 11.2% had NVL including 8.2% who experienced VF and 3.0% who interrupted ART. Younger age, male sex, less education, suboptimal adherence, receiving nevirapine, HIV non-disclosure, never having married and residing in Zimbabwe, Lesotho or Zambia were associated with higher odds of NVL. Among people with NVL, marriage, female sex, shorter ART duration, higher CD4 count and alcohol use were associated with lower odds for VF and higher odds for interrupted ART. Many people with VF (44.8%) had CD4 counts <200 cells/µL, but few (0.31% per year) switched to second-line ART. CONCLUSIONS Countries are approaching global VLS targets for adults. Treatment support, in particular for younger adults, and people with higher CD4 counts, and switching of people to protease inhibitor- or integrase inhibitor-based regimens may further reduce NVL prevalence

Quality evaluation of olive oil by statistical analysis of multicomponent stable isotope dilution assay data of aroma active compounds

An instrumental method for the evaluation of olive oil quality was developed. Twenty-one relevant aroma active compounds were quantified in 95 olive oil samples of different quality by headspace solid phase microextraction (HS-SPME) and dynamic headspace coupled to GC-MS. On the basis of these stable isotope dilution assay results, statistical evaluation by partial least-squares discriminant analysis (PLS-DA) was performed. Important variables were the odor activity values of ethyl isobutanoate, ethyl 2-methylbutanoate, 3-methylbutanol, butyric acid, E,E-2,4-decadienal, hexanoic acid, guaiacol, 2-phenylethanol, and the sum of the odor activity values of Z-3-hexenal, E-2-hexenal, Z-3-hexenyl acetate, and Z-3-hexenol. Classification performed with these variables predicted 88% of the olive oils? quality correctly. Additionally, the aroma compounds, which are characteristic for some off-flavors, were dissolved in refined plant oil. Sensory evaluation of these models demonstrated that the off-flavors rancid, fusty, and vinegary could be successfully simulated by a limited number of odorants

Prevalence of Trachoma in Unity State, South Sudan: Results from a Large-Scale Population-Based Survey and Potential Implications for Further Surveys

Large parts of South Sudan are thought to be trachoma endemic but baseline data, required to initiate interventions, are few. District-by-district surveys, currently recommended by the World Health Organization (WHO), are often not financially or logistically viable. We therefore adapted existing WHO guidelines and combined eight counties (equivalent to districts) of Unity State into one survey area, randomly sampling 40 villages using a population-based survey design. This decision was based on a trachoma risk map and a trachoma rapid assessment, both identifying the state as likely to be highly endemic. The survey confirmed trachoma as being hyperendemic throughout Unity State, meaning that large-scale intervention should be initiated now. Simulation studies were conducted to determine the likely outcome if fewer (n = 20) or more (n = 60) villages had been sampled, confirming that precision decreased or increased, respectively. Importantly, simulation results also showed that all three sample sizes would have led to the same conclusion, namely the need for large-scale intervention. This finding suggests that district-by-district surveys may not be required for areas where trachoma is suspected to be highly prevalent but that are lacking baseline data; instead districts may be combined into a larger survey area