RATIONALE: The causal relationship between undernutrition and response to anti-tuberculosis (TB) treatment and TB treatment outcomes among people with retreatment TB is understudied. OBJECTIVE: To evaluate the effect of undernutrition on treatment success and sputum smear conversion among people with retreatment drug-susceptible TB in Kampala, Uganda. METHODS: We conducted a quasi-experimental study utilizing propensity score weighting among people with retreatment drug-susceptible TB aged ≥ 15 years treated between 2012 and 2022 in Kampala. The primary exposure was undernutrition assessed using the mid-upper arm circumference at the time of TB diagnosis. The primary outcome was treatment success defined as cure or treatment completion at month 6. Sputum smear conversion was the secondary outcome and was measured as a change in sputum smear status from positive to negative at months 2, 5, and 6. We estimated the causal effect of undernutrition on the outcomes using a propensity-score weighted modified Poisson regression model with robust error variance. MEASUREMENTS AND MAIN RESULTS: Of the 605 participants, 432 (71.4 %) were male, 215 (35.5 %) were aged 25-34 years, 427 (70.6 %) had bacteriologically confirmed pulmonary TB, 133 (22.0 %) were undernourished and 398 (65.8 %) achieved treatment success. Of participants with bacteriologically confirmed pulmonary TB, 232 (59.0 %), 327 (59.3 %), and 360 (97.6 %) achieved sputum smear conversion at months 2, 5, and 6, respectively. Undernutrition reduced treatment success (RR 0.42, 95 % CI 0.32-0.55) as well as sputum smear conversion at months 2 (RR 0.45, 95 % CI 0.42-0.49) and 5 (RR 0.46, 95 % CI 0.43-0.51) but not month 6 (RR 0.99, 95 % CI 0.97-1.02). CONCLUSION: Undernutrition negatively impacts treatment outcomes. Therefore, nutritional assessment should be an integral component of TB care, with nutritional counseling and support offered to those undernourished to optimize their TB treatment response and outcomes.

Intensive adherence counseling (IAC) is recommended for people living with HIV (PLHIV) with viral load (VL) ≥1,000 copies/ml after ≥6 months of anti-retroviral therapy (ART). We evaluated the effect of IAC on VL suppression and all-cause mortality among PLHIV on first-line ART with VL ≥1,000 copies/ml after ≥6 months of ART in Kampala, Uganda using regression discontinuity design, a quasi-experimental method for effect estimation when interventions depend on a cut-off. PLHIV just above VL ≥1,000 copies/ml cut-off who received ≥3 IAC sessions formed the intervention group while those just below the cut-off who received routine psychosocial support constituted the control group. Primary outcome was repeat VL suppression defined as VL <1,000 copies/ml approximately 9-12 months following initial VL assessment. Secondary outcome was all-cause mortality. We used logistic regression for causal-effect analysis, reported as odds ratio (OR) with a 95% confidence interval (CI). We performed sensitivity analyses to assess the robustness of findings to varying bandwidths at the cut-off. We found 3,735 PLHIV were started on ART between Nov 2020 and Nov 2021 of whom 3,199 were included in the analysis (3,085 control, 114 intervention). Within an optimal bandwidth, there were 236 participants (222 control, 14 intervention) with similar demographic and clinical characteristics. Repeat VL suppression was lower in the intervention than in the control group (85.7% versus 98.6%, p = 0.021) while all-cause mortality was similar (0% versus 0.5%, p = 1.000). In multivariable analysis, the odds of repeat VL suppression were 91% lower in the intervention than control group (OR = 0.09; 95% CI, 0.01-0.66). Findings are robust to varying bandwidths around the cut-off. We concluded IAC is ineffective in suppressing VL among PLHIV on first-line ART in Kampala, Uganda. Findings suggest a need to investigate the IAC implementation fidelity for successful translation in practice and the reasons for VL persistence beyond the suppression threshold.

Background

Intensive adherence counseling (IAC) is the global standard of care for people living with human immunodeficiency virus (PLHIV) who have unsuppressed VL after ≥ 6 months of first-line anti-retroviral therapy (ART). We investigated whether the number of IAC sessions is associated with suppressed VL among PLHIV in Kampala, Uganda.

Methods

We conducted a nested case-control study among PLHIV with unsuppressed VL after ≥ 3 IAC sessions (cases) and a 2:1 random sample of PLHIV with suppressed VL after ≥ 3 IAC sessions (controls). Unsuppressed VL was defined as VL ≥ 1000 copies/ml. We performed multivariable logistic regression to identify factors that differed significantly between cases and controls.

Results

Demographic and clinical characteristics were similar among the 16 cases and 32 controls including mean age, sex, baseline CD4 count, VL before IAC, and WHO clinical stage. Only the number of IAC sessions differed significantly between cases and controls in unadjusted (p = 0.012) and adjusted (p = 0.016) analyses. Each unit increase in IAC session was associated with unsuppressed VL (Adjusted odds ratio 5.09; 95% CI 1.35-19.10).

Conclusions

VL remained unsuppressed despite increasing IAC frequency. The fidelity to standardized IAC protocol besides drug resistance testing among PLHIV with unsuppressed VL before IAC commencement should be examined.

The relationship between food insecurity and transactional sex is well recognized, but less is known about this relationship among adolescents. We analyzed cross-sectional baseline data from 3,130 female secondary students aged 12-19 enrolled in a three-arm, cluster randomized controlled trial to examine the association between food insecurity and transactional sex. The explanatory variable was food security and the outcome was ever engaging in transactional sex. Over one quarter (28.7%) reported any food insecurity and 1.9% of all participants (9.6% of sexually active participants) reported ever engaging in transactional sex. In adjusted models, ever experiencing any food insecurity was associated with a higher prevalence of ever transactional sex (PR: 1.60; 95% CI: 1.02, 2.49) compared to little to no food insecurity. These results provide insight into potential predictors of higher-risk sexual behavior in Rwanda; they also provide policy-makers with populations with whom to intervene on upstream determinants of transactional sex, notably poverty and food insecurity.

Appointment keeping and self-report within 7-day or and 30-days recall periods are non-objective measures of antiretroviral treatment (ART) adherence. We assessed incidence of virological failure (VF), predictive performance and associations of these adherence measures with VF among adults on long-term ART. Data for persons initiated on ART between April 2004 and April 2005, enrolled in a long-term ART cohort at 10-years on ART (baseline) and followed until December 2021 was analyzed. VF was defined as two consecutives viral loads ≥1000 copies/ml at least within 3-months after enhanced adherence counselling. We estimated VF incidence using Kaplan-Meier and Cox-proportional hazards regression for associations between each adherence measure (analyzed as time-dependent annual values) and VF. The predictive performance of appointment keeping and self-reporting for identifying VF was assessed using receiver operating characteristic curves and reported as area under the curve (AUC). We included 900 of 1,000 participants without VF at baseline: median age was 47 years (Interquartile range: 41-51), 60% were women and 88% were virally suppressed. ART adherence was ≥95% for all three adherence measures. Twenty-one VF cases were observed with an incidence rate of 4.37 per 1000 person-years and incidence risk of 2.4% (95% CI: 1.6%-3.7%) over the 5-years of follow-up. Only 30-day self-report measure was associated with lower risk of VF, adjusted hazard ratio (aHR) = 0.14, 95% CI:0.05-0.37). Baseline CD4 count ≥200cells/ml was associated with lower VF for all adherence measures. The 30-day self-report measure demonstrated the highest predictive performance for VF (AUC = 0.751) compared to appointment keeping (AUC = 0.674), and 7-day self-report (AUC = 0.687). The incidence of virological failure in this study cohort was low. Whilst 30- day self-report was predictive, appointment keeping and 7-day self-reported adherence measures had low predictive performance in identifying VF. Viral load monitoring remains the gold standard for adherence monitoring and confirming HIV treatment response.