Toward an Understanding of Disengagement from HIV Treatment and Care in Sub-Saharan Africa: A Qualitative Study

Background: The rollout of antiretroviral therapy in sub-Saharan Africa has brought lifesaving treatment to millions of HIV-infected individuals. Treatment is lifelong, however, and to continue to benefit, patients must remain in care. Despite this, systematic investigations of retention have repeatedly documented high rates of loss to follow-up from HIV treatment programs. This paper introduces an explanation for missed clinic visits and subsequent disengagement among patients enrolled in HIV treatment and care programs in Africa. Methods and Findings: Eight-hundred-ninety patients enrolled in HIV treatment programs in Jos, Nigeria; Dar es Salaam, Tanzania; and Mbarara, Uganda who had extended absences from care were tracked for qualitative research interviews. Two-hundred-eighty-seven were located, and 91 took part in the study. Interview data were inductively analyzed to identify reasons for missed visits and to assemble them into a broader explanation of how missed visits may develop into disengagement. Findings reveal unintentional and intentional reasons for missing, along with reluctance to return to care following an absence. Disengagement is interpreted as a process through which missed visits and ensuing reluctance to return over time erode patients' subjective sense of connectedness to care. Conclusions: Missed visits are inevitable over a lifelong course of HIV care. Efforts to prevent missed clinic visits combined with moves to minimize barriers to re-entry into care are more likely than either approach alone to keep missed visits from turning into long-term disengagement

Treatment Outcomes in a Decentralized Antiretroviral Therapy Program: A Comparison of Two Levels of Care in North Central Nigeria

Background. Decentralization of antiretroviral therapy (ART) services is a key strategy to achieving universal access to treatment for people living with HIV/AIDS. Our objective was to assess clinical and laboratory outcomes within a decentralized program in Nigeria. Methods. Using a tiered hub-and-spoke model to decentralize services, a tertiary hospital scaled down services to 13 secondary-level hospitals using national and program guidelines. We obtained sociodemographic, clinical, and immunovirologic data on previously antiretroviral drug naïve patients aged ≥15 years that received HAART for at least 6 months and compared treatment outcomes between the prime and satellite sites. Results. Out of 7,747 patients, 3729 (48.1%) were enrolled at the satellites while on HAART, prime site patients achieved better immune reconstitution based on CD4+ cell counts at 12 (P < 0.001) and 24 weeks (P < 0.001) with similar responses at 48 weeks (P = 0.11) and higher rates of viral suppression (<400 c/mL) at 12 (P < 0.001) and 48 weeks (P = 0.03), but similar responses at 24 weeks (P = 0.21). Mortality was 2.3% versus 5.0% (P < 0.001) at prime and satellite sites, while transfer rate was 8.7% versus 5.5% (P = 0.001) at prime and satellites. Conclusion. ART decentralization is feasible in resource-limited settings, but efforts have to be intensified to maintain good quality of care

Association of HIV-induced immunosuppression and clinical malaria in Nigerian adults

Background: Despite the growing body of evidence on the interaction between HIV and malaria in sub-Saharan Africa, there is a dearth of data on clinical malaria in HIV-infected patients in Nigeria. We determined the burden of clinical malaria in HIV-infected adult Nigerians and further investigated the association between their immunological status and the rates of clinical malaria. Methods: Ninety seven antiretroviral treatment-naïve HIV-infected adults were enrolled in a cross-sectional study from August to December, 2009. The participants had a complete clinical evaluation, thick and thin blood films for malaria parasites and CD4 cell count quantification. Clinical malaria was defined as having fever (temperature ≥ 37.5oC or history of fever within 48 hours) and a malaria parasite density above the median value obtained for subjects with co-existing fever and parasitaemia. Results: Clinical malaria was diagnosed in 10 out of 97 patients (10.3%). Lower CD4 cell counts were associated with increasing rates of clinical malaria which was 0% at CD4 cell count of ≥ 500, 2.6% at 200-499 and 30% a

Treatment Outcomes Among Older Human Immunodeficiency Virus-Infected Adults in Nigeria

Abstract Background. Older age at initiation of combination antiretroviral therapy (cART) has been associated with poorer clinical outcomes. Our objectives were to compare outcomes between older and younger patients in our clinical cohort in Jos, Nigeria. Methods. This retrospective cohort study evaluated patients enrolled on cART at the Jos University Teaching Hospital, Nigeria between 2004 and 2012. We compared baseline and treatment differences between older (≥50 years) and younger (15–49 years) patients. Kaplan-Meier analysis and Cox proportional hazard models estimated survival and loss to follow-up (LTFU) and determined factors associated with these outcomes at 24 months. Results. Of 8352 patients, 643 (7.7%) were aged ≥50 years. The median change in CD4 count from baseline was 151 vs 132 (P = .0005) at 12 months and 185 vs 151 cells/mm3 (P = .03) at 24 months for younger and older patients, respectively. A total of 68.9% vs 71.6% (P = .13) and 69.6% vs 74.8% (P = .005) of younger and older patients achieved viral suppression at 12 and 24 months, with similar incidence of mortality and LTFU. In adjusted hazard models, factors associated with increased risk of mortality were male sex, World Health Organization (WHO) stage III/IV, and having a gap in care, whereas being fully suppressed was protective. The risk of being LTFU was lower for older patients, those fully suppressed virologically and with adherence rates >95%. Male sex, lack of education, WHO stage III/IV, body mass index <18.5 kg/m2, and having a gap in care independently predicted LTFU. Conclusions. Older patients achieved better viral suppression, and older age was not associated with increased mortality or LTFU in this study

Patient Experiences of Decentralized HIV Treatment and Care in Plateau State, North Central Nigeria: A Qualitative Study

Background. Decentralization of care and treatment for HIV infection in Africa makes services available in local health facilities. Decentralization has been associated with improved retention and comparable or superior treatment outcomes, but patient experiences are not well understood. Methods. We conducted a qualitative study of patient experiences in decentralized HIV care in Plateau State, north central Nigeria. Five decentralized care sites in the Plateau State Decentralization Initiative were purposefully selected. Ninety-three patients and 16 providers at these sites participated in individual interviews and focus groups. Data collection activities were audio-recorded and transcribed. Transcripts were inductively content analyzed to derive descriptive categories representing patient experiences of decentralized care. Results. Patient participants in this study experienced the transition to decentralized care as a series of &quot;trade-offs.&quot; Advantages cited included saving time and money on travel to clinic visits, avoiding dangers on the road, and the &quot;family-like atmosphere&quot; found in some decentralized clinics. Disadvantages were loss of access to ancillary services, reduced opportunities for interaction with providers, and increased risk of disclosure. Participants preferred decentralized services overall. Conclusion. Difficulty and cost of travel remain a fundamental barrier to accessing HIV care outside urban centers, suggesting increased availability of community-based services will be enthusiastically received

Hepatitis B Co-Infection is Associated with Poorer Survival of HIV-Infected Patients on Highly Active Antiretroviral Therapy in West Africa

Background: Hepatitis B has been reported to be high in HIV-infected African populations. However, the impact of this co-infection on the survival of HIV-infected Africans on long-term highly active antiretroviral therapy (HAART) remains poorly characterised. We investigated the impact of HBV/HIV co-infection on survival of HIV infected patients undergoing antiretroviral therapy in a West African population. Methods: This was a clinic-based cohort study of HIV-infected adults enrolled in Nigeria, West Africa. Study subjects (9,758) were screened for hepatitis B and hepatitis C at HAART initiation. Kaplan-Meier survival and Cox proportional hazards models were used to estimate probability of survival and to identify predictors of mortality respectively, based on hepatitis B surface antigen status. All patients had signed an informed written consent before enrolment into the study; and we additionally obtained permission for secondary use of data from the Harvard institutional review board. Results: Patients were followed up for a median of 41 months (interquartile range: 30–62 months) during which, 181 (1.9%) patients died. Most of the deaths; 143 (79.0%) occurred prior to availability of Tenofovir. Among those that were on antiretroviral therapy, hepatitis B co-infected patients experienced a significantly lower survival than HIV mono-infected patients at 74 months of follow up (94% vs. 97%; p=0.0097). Generally, hepatitis B co-infection: HBsAg-positive/HIV-positive (Hazards Rate [HR]; 1.5: 95% CI 1.09–2.11), co-morbid tuberculosis (HR; 2.2: 95% CI 1.57–2.96) and male gender (HR; 1.5: 95% CI 1.08–2.00) were significantly predictive of mortality. Categorising the patients based on use of Tenofovir, HBV infection failed to become a predictor of mortality among those on Tenofovir-containing HAART. Conclusions: HBsAg-positive status was associated with reduced survival and was an independent predictor of mortality in this African HIV cohort on HAART. However, Tenofovir annulled the impact of HBV on mortality of HIV patients in the present study cohort

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Prevalence of self-reported hypertension and diabetes and associated risk factors among university employees in Jos, Nigeria

Background: Non-communicable diseases (NCD) are emerging, and their risk factors are becoming more common as lifestyles change and rates of urbanization increase. We determined the prevalence of self-reported hypertension and diabetes mellitus (DM) and their relationship to common NCD risk factors among university employees.Methods: This was a cross-sectional study of 884 adults employed at the University of Jos, Nigeria. They were evaluated using the Step 1 of the WHO-STEPS questionnaire. We used logistic regression analysis to evaluate the common NCD risk factors associated with self-reported hypertension and DM.Results: Significant alcohol consumption was present in 77 (8.7%) while 26 (2.5%) were current cigarette smokers. Two hundred and seventy nine (31.5%) engaged in moderate intensity exercises like brisk walking and cycling for 10 minutes on a regular basis. The median weekly fruit and vegetable intake were 3 times (range 0-8) and 3 times (range 0-7) respectively. A total of 333 (39.7%) and 64 (7.3%) participants had a prior diagnosis of hypertension and DM respectively. Self-reported hypertension was associated with the female sex (OR = 2.30; 95% CI: 1.65-3.19), increasing age (OR = 1.08; 95% CI: 1.06-1.10) and alcohol use (OR=1.38; 95% CI: 1.00- 1.91), while self-reported DM was associated with increasing age (OR = 1.08; 95% CI: 1.05-1.12). Neither hypertension nor DM was associated with physical activity, smoking status or fruit and vegetable intake.Conclusion: This study provides evidence on self-reported NCDs in a developing economy. Concerted efforts to implement NCD prevention measures will serve to reduce the high burden of NCDs.Keywords: Non-communicable disease, Diabetes mellitus, Hypertension, Lifestyle, risk factor

Awareness and knowledge of human immunodeficiency virus post exposure prophylaxis among Nigerian Family Physicians

Background: To determine the level of awareness and knowledge of HIV postexposure prophylaxis (HIV PEP) and determinants of adequate knowledge among Family Physicians in Nigeria. Materials and Methods: This was a cross‑sectional questionnaire‑based survey conducted among 175 Family Physicians at two national conferences. Results: Majority (97.7%) of the respondents was aware of the concept of HIV PEP and 99.4% believed it was effective in preventing HIV transmission. Over two third of our respondents had been exposed to NSI; however, less than 25% of those exposed received PEP. There was high level of knowledge of the various high‑risk body fluids as well as types of high‑risk exposures. 93.9% of our respondents knew that HIV PEP should commence within 1 h of exposure, 83.3% knew the correct duration of HIV PEP, but only 57.0% knew the ideal PEP regimen for high‑risk exposures. The total mean score for our respondents was 17.8±2.9 with 79.4% having an adequate score. Being a junior doctor and male sex were associated with adequate knowledge. Conclusion: This study shows that despite high levels of awareness and knowledge of HIV PEP, access to its use among family physicians in Nigeria is still sub‑optimal.Keywords: Family physicians, HIV PEP, NigeriaNigerian Medical Journal | Vol. 53 | Issue 3 | July-September | 201