Treatment Outcomes for Tuberculosis Infection and Disease Among Persons Deprived of Liberty, Uganda, 2020.

We report that unsuccessful treatment outcomes were 11.8% for tuberculosis (TB) disease and 21.8% for TB infection among persons deprived of liberty in Uganda Prisons Service facilities. Remedial efforts should include enhancing referral networks to ensure treatment continuity, strengthening data systems for complete outcome documentation, and prioritizing short-course treatment regimens.

Provision of cervical cancer services for women living with HIV, Uganda.

Objective: To describe the scale-up of cervical cancer screening and treatment for women living with human immunodeficiency virus (HIV), aged 25-49 years in Uganda, and to analyse the programme data. Methods: The health ministry targeted existing HIV clinics in a 2-year scale-up of cervical cancer screening services from October 2020. In preparation, we trained health workers to assess women attending HIV clinics for screening eligibility, provided either by human papillomavirus (HPV) testing and/or visual inspection with acetic acid. Clinic staff treated women with precancerous cervical lesions with thermocoagulation or referred women with suspected cancer to external services. We analysed data reported every 6 months for the number of clinics offering screening, screening uptake, the number of positive diagnoses and the number of women who received treatment. Findings: The number of HIV clinics offering cervical cancer screening services increased from 11, before the programme launch, to 1571. During the programme, screening uptake increased from 5.0% (6506/130 293) to 107.3% (151 872/141 527) of targets. The cumulative proportion of positive diagnoses was 5.9% (23 970/407 323) overall, but was much lower for screening offering visual inspection only compared with clinics offering HPV testing. Although the proportion of women receiving treatment if positive increased from 12.8% (53/413) to 84.3% (8087/9592), the World Health Organization target of 90% was not reached. Conclusion: We demonstrated marked increases, potentially replicable by other countries, in screening and treatment. These increases could be improved further by expanding HPV testing and same-day treatment of precancerous lesions.

Impact of an intensive facility-community case management intervention on 6-month HIV outcomes among select key and priority populations in Uganda.

INTRODUCTION: Key and priority populations (with risk behaviours and health inequities) are disproportionately affected by HIV in Uganda. We evaluated the impact of an intensive case management intervention on HIV treatment outcomes in Kalangala District, predominantly inhabited by fisher folk and female sex workers. METHODS: This quasi-experimental pre-post intervention evaluation included antiretroviral therapy naïve adults aged ≥ 18 years from six health facilities in the pre-intervention (Jan 1, 2017-December 31, 2017) and intervention phase (June 13, 2018-June 30, 2019). The primary outcomes were 6-month retention and viral suppression (VS) before and after implementation of the intervention involving facility and community case managers who supported participants through at least the first three months of ART. We used descriptive statistics to compared the characteristics, overall outcomes (i.e., retention, lost to follow up, died), and VS of participants by phase, and used mixed-effects logistic regression models to determine factors associated with 6-month retention in care. Marginal (averaging over facilities) probabilities of retention were computed from the final multivariable model. RESULTS: We enrolled 606 and 405 participants in the pre-intervention and intervention phases respectively. Approximately 75% of participants were aged 25-44 years, with similar age and gender distributions among phases. Approximately 46% of participants in the intervention were fisher folk and 9% were female sex workers. The adjusted probability of 6-month retention was higher in the intervention phase, 0.83 (95% CI: 0.77-0.90) versus pre-intervention phase, 0.73 (95% CI: 0.69-0.77, p = 0.03). The retention probability increased from 0.59 (0.49-0.68) to 0.73 (0.59-0.86), p = 0.03 among participants aged 18-24 years, and from 0.75 (0.71-0.78) to 0.85 (0.78-0.91), p = 0.03 among participants aged ≥ 25 years. VS (< 1,000 copies/mL) was approximately 87% in both phases. CONCLUSIONS: After implementation of the case management intervention, we observed significant improvement in 6-month retention in all age groups of a highly mobile population of predominantly fisher folk.

Cryptococcal Antigenemia in Human Immunodeficiency Virus Antiretroviral Therapy-Experienced Ugandans With Virologic Failure.

BACKGROUND: Detectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization recommends CrAg screening for human immunodeficiency virus-positive persons with CD4 count <100 cells/µL initiating antiretroviral therapy (ART). However, an increasing proportion of patients with cryptococcosis are now ART experienced. Whether CrAg screening is cost-effective in those with virologic failure is unknown. METHODS: We retrospectively performed nationwide plasma CrAg testing among ART-experienced Ugandan adults with virologic failure (≥1000 copies/mL) using leftover plasma after viral load testing during September 2017-January 2018. For those who were CrAg positive, we obtained ART history, meningitis occurrence, and 6-month survival via medical records review. RESULTS: Among 1186 subjects with virologic failure, 35 (3.0%) were CrAg positive with median ART duration of 41 months (interquartile range, 10-84 months). Among 25 subjects with 6-month outcomes, 16 (64%) survived, 7 (28%) died, and 2 (8%) were lost. One survivor had suffered cryptococcal meningitis 2 years prior. Two others developed cryptococcal meningitis and survived. Five survivors were known to have received fluconazole. Thus, meningitis-free survival at 6 months was 61% (14/23). Overall, 91% (32/35) of CrAg-positive persons had viral load ≥5000 copies/mL compared with 64% (735/1151) of CrAg-negative persons (odds ratio, 6.0 [95% confidence interval, 1.8-19.8]; P = .001). CrAg prevalence was 4.2% (32/768) among those with viral loads ≥5000 copies/mL and 0.7% (3/419) among those with viral loads <5000 copies/mL. CONCLUSIONS: In addition to the CD4 threshold of <100 cells/µL, reflexive CrAg screening should be considered in persons failing ART in Uganda with viral loads ≥5000 copies/mL.

Determinants of HIV counseling and testing uptake among individuals in long-term sexual relationships in Uganda.

INTRODUCTION: Studies show that HIV counseling and testing (HCT) can improve linkage to HIV prevention, care and treatment services. However, uptake of HCT among couples remains low in most settings. We investigated the determinants of HCT uptake among individuals in long-term relationships in two districts in Uganda. METHODS: This case-control study was conducted among 787 (400 in Kampala and 387 in Soroti) individuals in long-term sexual relationships, aged 18-54 years, using interviewer-administered questionnaires. Cases were individuals who had ever tested for HIV (selected from health facility records and traced in the community for interview) while controls were individuals who had never tested for HIV, identified from the same community as the cases. Data were collected on sociodemographic and behavioral characteristics; entered into FoxPro and analyzed using STATA version 12.1. We performed multivariable logistic regression to estimate the odds ratio (OR) and 95% Confidence Intervals (95%CI) associated with prior HCT and couples' HCT uptake, controlling for suspected confounders. RESULTS: Of the 787 participants, 522 had ever tested for HIV (cases) while 265 had never tested for HIV (controls). Compared to those that had never tested for HIV, those that had ever tested for HIV were significantly more likely to be females (Adj. OR=3.23, 95%CI: 2.27, 4.60), to be 25-29 years old (Adj. OR=2.15, 95%CI: 1.32, 3.50), to report exposure to a couples' HCT promotional campaign (Adj. OR=2.01, 95%CI: 1.30, 3.10) and to believe that HIV discordance is possible among married couples (Adj. OR=1.77, 95%CI: 1.20, 2.63). Compared to individuals that had ever received individual HCT, those that had ever received couples' HCT were significantly more likely to report prior discussion of HIV testing with partner (Adj. OR=4.35, 95%CI: 2.61, 7.28) and to be residents of Soroti district (Adj. OR=6.01, 95%CI: 3.74, 9.65). CONCLUSION: Prior HCT was significantly associated with female gender and exposure to a couples' HCT promotional campaign while prior couples' HCT was significantly associated with prior discussion of HIV testing with partner. To increase HIV testing among couples, these findings suggest a need for HCT promotional campaigns that promote communication about HCT between partners.

Sexual behavior among persons living with HIV in Uganda: implications for policy and practice.

INTRODUCTION: HIV epidemics are sustained and propagated by new cases of infection which result from transmission from infected persons to uninfected susceptible individuals. People living with HIV (PLHIV) play a critical role in prevention if they adopt safer sexual behaviors. This study estimated the prevalence of and factors associated with safer sexual behaviors among PLHIV seeking care from civil society organizations (CSOs). METHODS: In a cross sectional study PLHIV were interviewed about their sexual practices, use of alcohol, HIV status of their regular sexual partners, desire for more children and about their socio-demographic characteristics. We calculated the proportion of PLHIV who abstained and consistently used condoms in the previous twelve months. Independent associations between safer sex and other variables were estimated using adjusted prevalence ratios (aPR) and their 95% confidence intervals (CI). RESULTS: Of the 939 PLHIV, 54% (508) were either abstaining or using condoms consistently and 291 (31%) desired more children. The prevalence of consistent condom use among the sexually active was 41.3% (300/731). Consistent condom use was higher among PLHIV who: didn't use alcohol (aPR 1.30, CI 1.03-1.63); were educated about re-infection with a new strain of HIV (aPR 1.84, CI 1.08-3.12) and had regular sexual partner who was HIV negative (aPR 1.29, CI 1.05-1.57). Prevalence of abstinence was 22.2% (208/939). Abstinence increased with age from 9.4% among PLHIV <25 years to 40.5% among those >50 years. Abstinence was extremely low (2.5%) among PLHIV who were married. CONCLUSIONS: Effective interventions that reduce alcohol consumption among PLHIV are needed to avert HIV transmission, prevent acquisition of new HIV strains and STIs. In addition, strategies are needed to address needs of PLHIV who desire more children.

Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.

BACKGROUND: Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy. METHODS: This analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/µL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1-infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list. RESULTS: Perinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. CONCLUSIONS: Infants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.

Poor immunological recovery among severely immunosuppressed antiretroviral therapy-naïve Ugandans.

INTRODUCTION: CD4 T lymphocytes remain the surrogate measure for monitoring HIV progress in resource-limited settings. The absolute CD4 cell counts form the basis for antiretroviral therapy (ART) initiation and monitoring among HIV-infected adults. However, the rate of CD4 cell change differs among patients, and the factors responsible are inadequately documented. OBJECTIVE: This study investigated the relationship between HIV severity and ART outcomes among ART-naïve Ugandans, with the primary outcome of complete immunological recovery among patients of different baseline CD4 counts. METHODS: Patients' records at two HIV/ART sites - the Joint Clinic Research Centre (JCRC) in the Kampala region and Mbarara Hospital in Western Uganda - were reviewed. Records of 426 patients - 68.3% female and 63.2% from JCRC - who initiated ART between 2002 and 2007 were included. HIV severity was based on baseline CD4 cell counts, with low counts considered as severe immunosuppression, while attaining 418 CD4 cells/µL signified complete immunological recovery. Incidence rates of complete immunological recovery were calculated for, and compared between baseline CD4 cell categories: <50 with ≥50, <100 with ≥100, <200 with ≥200, and ≥200 with ≥250 cells/µL. RESULTS: The incidence of complete immunological recovery was 158 during 791.9 person-years of observation, and patients with baseline CD4 ≥ 200 cells/µL reached the end point of immunological recovery 1.89 times faster than the patients with baseline CD4 < 200 cells/µL. CD4 cell change also differed by time, sex, and site, with a faster increase observed during the first year of treatment. CD4 cell increase was faster among females, and among patients from Mbarara. CONCLUSION: Initiating ART at an advanced HIV stage was the main reason for poor immunological recovery among Ugandans. Earlier ART initiation might lead to better immunological responses.

Clinical and genetic determinants of plasma nevirapine exposure following an intrapartum dose to prevent mother-to-child HIV transmission.

OBJECTIVE: Nevirapine is metabolized by cytochrome P450 (CYP) 2B6 and CYP3A4. We characterized relationships between clinical parameters, human genetics, pharmacokinetics, and human immunodeficiency virus type 1 (HIV-1) drug resistance mutations in pregnant women following single-dose intrapartum nevirapine. METHODS: In AIDS Clinical Trials Group study A5207, women received nevirapine at onset of labor and were randomly assigned to receive lamivudine/zidovudine, emtricitabine/tenofovir, or lopinavir/ritonavir for 7 or 21 days. Plasma nevirapine level was quantified on postpartum day 1 and on weeks 1, 3, and 5. We assayed 214 polymorphisms in CYP2B6 and other genes and evaluated associations with pharmacokinetic parameters, including elimination constant, time to protein-adjusted 50% inhibitory concentration (IC50), and week 5 nevirapine level below the quantification limit. RESULTS: Among 301 women with evaluable pharmacokinetic and genotype data, lower body mass index and random assignment to receive lopinavir/ritonavir were associated with more rapid nevirapine elimination. Among those of African ancestry, longer time to IC50 was associated with CYP2B6 983T → C (P = .004) but not with CYP2B6 516G → T (P = .8). Among Indians, slower nevirapine elimination was associated with CYP2B6 516G → T (P = .04). Emergent resistance was infrequent and not associated with pharmacokinetics or CYP2B6 genotype. CONCLUSIONS: The effects on plasma drug exposure following single-dose nevirapine may be greater for CYP2B6 983T → C than for 516G → T and are less pronounced than at steady state.

Greater suppression of nevirapine resistance with 21- vs 7-day antiretroviral regimens after intrapartum single-dose nevirapine for prevention of mother-to-child transmission of HIV.

BACKGROUND: Nevirapine (NVP) resistance emerges in up to 70% of women exposed to single-dose (sd) NVP for prevention of mother-to-child transmission of human immunodeficiency virus (HIV). METHODS: HIV-infected pregnant women were randomized to receive sdNVP and either zidovudine/lamivudine (3TC), tenofovir/emtricitabine (FTC), or lopinavir/ritonavir for either 7 or 21 days. The primary endpoint was the emergence of new NVP resistance mutations as detected by standard population genotype at 2 and 6 weeks after treatment. Low-frequency NVP- or 3TC/FTC-resistant mutants at codons 103, 181, and 184 were sought using allele-specific polymerase chain reaction (ASP). RESULTS: Among 484 women randomized, 422 (87%) received study treatment. Four hundred twelve (98%) women had primary endpoint results available; of these, 5 (1.2%) had new NVP resistance detected by population genotype: 4 of 215 in the 7-day arms (1.9%; K103N in 4 women with Y181C, Y188C, or G190A in 3 of 4) and 1 of 197 (0.5%; V108I) in the 21-day arms (P = .37). Among women with ASP results, new NVP resistance mutations emerged significantly more often in the 7-day arms (13/74 [18%]) than in the 21-day arms (3/66 [5%], P = .019). 3TC/FTC-resistant mutants (M184V/I) emerged infrequently (7/134 [5%]), and their occurrence did not differ by arm. CONCLUSIONS: Three short-term antiretroviral strategies, begun simultaneously with the administration of sdNVP, resulted in a low rate (1.2%) of new NVP-resistance mutations when assessed at 2 and 6 weeks following completion of study treatment by standard genotype. ASP revealed that 21-day regimens were significantly better than 7-day regimens at preventing the emergence of minor NVP resistance variants. Clinical Trials Registration.NCT00099632.