Antiretroviral Treatment In Uganda Research Articles

A Qualitative Exploration of Causes of Depression among Persons Living with HIV Receiving Antiretroviral Therapy in Uganda: Implications for Policy.

Depression is the fourth leading cause of the global disease burden and worsens the outcome of comorbidities including HIV/AIDS. Depression is particularly problematic among persons living with HIV in sub-Saharan Africa where scarcity of cost-effective interventions is compounded by inadequate understanding of the disease. We examine risk factors for depression among persons living with HIV undergoing antiretroviral treatment in Uganda and discuss policy implications. A qualitative study using a narrative approach was conducted, the formative phase of a large study to develop a model for integrating depression management into routine HIV care in Uganda. Participants were purposively sampled at four public health facilities in Mpigi District. In-depth interviews were conducted with four clinicians, three supervisors, and 11 persons living with HIV and suffering from depression, as were three focus group discussions with lay health workers. Exit interviews were conducted with 17 persons living with HIV who completed/interrupted depression treatment but had not been interviewed. Only data collected from persons living with HIV and lay health workers were analysed for the purpose of this paper. A narrative thematic approach was used in data analysis. Findings. There were several pathways through which lack of family social support reportedly led to depression: worries about disclosure in discordant relationships, false perceptions of social support, stigmatisation and discrimination, and domestic violence. Economic/poverty and other causes were identified, but their role was less significant or moderated by family social support. Family social support plays a dominant role-both directly and indirectly-in influencing depression risk. We propose the mainstreaming of formal psychosocial support and a shift from individual to family-focused counselling that targets both persons living with HIV and their family.

Discontinuing cotrimoxazole preventive therapy in HIV-infected adults who are stable on antiretroviral treatment in Uganda (COSTOP): A randomised placebo controlled trial.

BackgroundCotrimoxazole (CTX) preventive therapy (CPT) reduces opportunistic infections and malaria in HIV-infected patients. In Africa, policies on sustained CPT during antiretroviral therapy (ART) differ between countries. We assessed the safety of discontinuing CPT in stable patients on ART in Uganda.MethodsCOSTOP was a double-blind placebo-controlled trial. Patients aged ≥18 years, on CPT, and stable on ART (CD4 counts ≥250 cells/μL); were randomised to daily oral placebo (PLC group) or cotrimoxazole 960 mg/tablet (CTX group). Co-primary outcomes were: (i) time to first cotrimoxazole-preventable infection, with non- inferiority of PLC defined as the upper one-sided 95% confidence limit of the adjusted hazard ratio(aHR) ≤1.25; and (ii) time to first grade 3/4 haematological adverse event.Findings2180 subjects (1091 PLC; 1089 CTX) were enrolled. 932 PLC and 943 CTX completed the trial after 12 months minimum follow up. Ninety-eight participants (59 PLC; 39 CTX) experienced 120 cotrimoxazole- preventable events, mainly bacterial pneumonia (72 events, 4 deaths PLC); (48 events, 2 deaths CTX). The aHR for time to first event was 1.57 (upper one-sided 95% confidence limit 2.21) in per protocol population (similar results in ITT population). 551 participants (318 CTX; 233 PLC) experienced 1043 haematological adverse events (616 CTX; 427 PLC). Time to the first adverse event, mainly neutropenia, was shorter in the CTX group (aHR 0.70 95%CI 0.59–0.82; log-rank χ2 = 18.08; P<0.0001). 362 (276 PLC, 86 CTX) participants experienced at least one episode of confirmed clinical malaria (P<0.0001).InterpretationIn ART stable patients with CD4 counts ≥250 cells/μL, continued CPT significantly reduces risk of severe bacterial infections and protects against malaria, while discontinuing CPT reduces haematological adverse events.

Risky sexual behavior among patients on\xa0long-term antiretroviral therapy: a prospective cohort study in urban and rural Uganda

BackgroundWhile the effects of initiation of antiretroviral treatment (ART) on risky sexual behavior have been extensively studied, less is known about the long-term changes in risky sexual behavior over time in resource-poor settings.MethodsWe conducted a secondary longitudinal analysis of one rural and one urban cohort of patients who initiated ART in Uganda between April 2004 and July 2007 followed up-to 2016. Data on sexual behavior were collected every 6 months for 3.5 years in individuals on ART ≥ 4 years (baseline) when a behavioral questionnaire was introduced. Risky sexual behavior was defined as sexual intercourse with ≥ 2 partners or inconsistent or no condom use in previous 6 months. We report characteristics overall, and by cohort. We used multivariable generalized estimating equations logistic regression to assess the effects of time on ART on risky sexual behavior.ResultsOf 1012 participants, 402 (39.8%) were urban and 610 (60.2%) were rural residents. Mean age was 42.8 years (SD 8.5). Mean duration of follow-up was 51.3 months (SD 15.3), but longer for urban than rural participants (64.5 vs 36.4 months). Risky sexual behavior declined from 33.1% at baseline to 9.6% after 3.5 years of follow-up in the rural cohort (p ≤ 0.01 for the test of trend) and was unchanged from 9.7% at baseline to 9.9% after 3.5 years in the urban cohort (p = 0.51). Receiving care at a rural clinic (aOR 4.99, 95% CI 3.64–6.84); male gender (aOR 1.66, 95% CI 1.26–2.19) and being younger (aOR 5.60, 95% CI 3.80–8.25 for 18–34 years and aOR 2.34, 95% CI 1.74–3.14 for 35–44 years) were associated with increased odds of risky sexual behavior. Not being married (aOR 0.25; 95% CI 0.19–0.34), and longer time on ART (aOR 0.71 95% CI 0.67–0.76) were associated with reduced odds of risky sex.ConclusionsWe observed a decline in risky sexual behavior in rural people on long-term (≥ 4 years) ART. Rural, male and young individuals had higher odds of self-reported risky sexual behavior. ART programs should continue to emphasize risk reduction practices, especially among people receiving care in rural health facilities, males, younger individuals and those who are married.

Low-Frequency Drug Resistance in HIV-Infected Ugandans on Antiretroviral Treatment Is Associated with Regimen Failure.

Most patients failing antiretroviral treatment in Uganda continue to fail their treatment regimen even if a dominant drug-resistant HIV-1 genotype is not detected. In a recent retrospective study, we observed that approximately 30% of HIV-infected individuals in the Joint Clinical Research Centre (Kampala, Uganda) experienced virologic failure with a susceptible HIV-1 genotype based on standard Sanger sequencing. Selection of minority drug-resistant HIV-1 variants (not detectable by Sanger sequencing) under antiretroviral therapy pressure can lead to a shift in the viral quasispecies distribution, becoming dominant members of the virus population and eventually causing treatment failure. Here, we used a novel HIV-1 genotyping assay based on deep sequencing (DeepGen) to quantify low-level drug-resistant HIV-1 variants in 33 patients failing a first-line antiretroviral treatment regimen in the absence of drug-resistant mutations, as screened by standard population-based Sanger sequencing. Using this sensitive assay, we observed that 64% (21/33) of these individuals had low-frequency (or minority) drug-resistant variants in the intrapatient HIV-1 population, which correlated with treatment failure. Moreover, the presence of these minority HIV-1 variants was associated with higher intrapatient HIV-1 diversity, suggesting a dynamic selection or fading of drug-resistant HIV-1 variants from the viral quasispecies in the presence or absence of drug pressure, respectively. This study identified low-frequency HIV drug resistance mutations by deep sequencing in Ugandan patients failing antiretroviral treatment but lacking dominant drug resistance mutations as determined by Sanger sequencing methods. We showed that these low-abundance drug-resistant viruses could have significant consequences for clinical outcomes, especially if treatment is not modified based on a susceptible HIV-1 genotype by Sanger sequencing. Therefore, we propose to make clinical decisions using more sensitive methods to detect minority HIV-1 variants.

HIV Drug Resistance Among Children Initiating First-Line Antiretroviral Treatment in Uganda.

Background: There are limited data on primary human immunodeficiency virus drug resistance (HIVDR) in pediatric populations. This study aimed to assess the prevalence of primary HIVDR and associated risk factors among children initiating first-line antiretroviral therapy (ART) in Uganda.Methods: At three Ugandan clinics, children (age <12 years) requiring ART were recruited between January 2010 and August 2011. Before starting ART, blood was collected for viral load and pol gene sequencing. Drug resistance mutations were determined using the 2010 International AIDS Society–USA mutation list. Risk factors for HIVDR were assessed with multivariate regression analysis.Results: Three hundred nineteen HIV-infected children with a median age of 4.9 years were enrolled. Sequencing was successful in 279 children (87.5%). HIVDR was present in 10% of all children and 15.2% of children <3 years. Nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTI (NNRTI), and dual-class resistance was present in 5.7%, 7.5%, and 3.2%, respectively. HIVDR occurred in 35.7% of prevention of mother-to-child transmission (PMTCT)–exposed children, 15.6% in children with unknown PMTCT history, and 7.7% among antiretroviral-naive children. History of PMTCT exposure [adjusted odds ratio (AOR): 2.6, 95% CI: 1.3–5.1] or unknown PMTCT status (AOR: 3.8, 95% CI: 1.1–13.5), low CD4 (AOR: 2.2, 95% CI: 1.3–3.6), current breastfeeding (AOR: 7.4, 95% CI: 2.6–21), and current maternal ART use (AOR: 6.4, 95% CI: 3.4–11.9) emerged as risk factors for primary HIVDR in multivariate analysis.Conclusion: Pretreatment HIVDR is high, especially in children with PMTCT exposure. Protease inhibitor (PI)–based regimens are advocated by the World Health Organization, but availability in children is limited. Children with (unknown) PMTCT exposure, low CD4 count, current breastfeeding, or maternal ART need to be prioritized to receive PI-based regimens.

Higher quality of life and lower depression for people on ART in Uganda as compared to a community control group.

Provision of antiretroviral treatment (ART) to people living with HIV (PLWH) has increased globally. Research measuring whether ART restores subjective well-being to “normal” levels is lacking, particularly in resource limited settings. The study objectives are to compare quality of life and depression symptoms for PLWH on ART to a general community population and to explore factors to explain these differences, including socio-economic status and the impact of urban or rural residence. PLWH on ART (n = 263) were recruited from ART delivery sites and participants not on ART (n = 160) were recruited from communities in Wakiso District, Uganda. Participants were interviewed using the translated World Health Organisation Quality of Life brief measure, the Hopkins Symptom Checklist depression section, and questions about socio-economic status, residence as urban or rural and, for PLWH on ART, self-reported adherence and use of HIV counselling. Compared to the community sample and controlling for location of residence, PLWH on ART had significantly higher quality of life (QOL) for physical, psychological and environment domains, but not the social domain. These differences were not due to socio-economic status alone. Depression scores were significantly lower for PLWH on ART. Both comparisons controlled for the effect of location of residence. People on ART self-reported high adherence and the majority had used HIV counselling services. Our findings show better QOL amongst PLWH on ART compared to a general community sample, which cannot be explained solely by differences in socio-economic status nor location of residence. The general community sample results point towards the challenges of life in this setting. Access to health services may underpin this difference and further research should explore this finding, in addition to identification of psychological mechanisms that relate to better QOL. ART provision infrastructure has clear benefits. Further work should consider sustainability and replication for other health conditions.

Improving adherence to antiretroviral treatment in Uganda with a low-resource facility-based intervention

ObjectiveTo assess the effects of facility-based interventions using existing resources to improve overall patient attendance and adherence to antiretroviral therapy (ART) at ART-providing facilities in Uganda.MethodsThis was an interventional study which tracked attendance and treatment adherence of two distinct cohorts: experienced patients who had been on treatment for at least 12 months prior to the intervention and patients newly initiated on ART before or during the intervention. The interventions included instituting appointment system, fast-tracking, and giving longer prescriptions to experienced stable patients. Mixed-effects models were used to examine intervention effects on the experienced patients, while Cox proportional hazards models were used to determine the intervention effects on time until newly treated patients experienced gaps in medication availability.ResultsIn all, 1481 patients’ files were selected for follow-up from six facilities – 720 into the experienced cohort, and 761 into the newly treated cohort. Among patients in the experienced cohort, the interventions were associated with a significant reduction from 24.4 to 20.3% of missed appointments (adjusted odds ratio (AOR): 0.67; 95% confidence interval (CI): 0.59–0.77); a significant decrease from 20.2 to 18.4% in the medication gaps of three or more days (AOR: 0.69; 95% CI: 0.60–0.79); and a significant increase from 4.3 to 9.3% in the proportion of patients receiving more than 30 days of dispensed medication (AOR: 2.35; 95% CI: 1.91–2.89). Among newly treated patients, the interventions were associated with significant reductions of 44% (adjusted hazard rate (AHR): 0.56, 95% CI: 0.42–0.74) and 38% (AHR: 0.62; 95% CI: 0.45–0.85) in the hazards of experiencing a medication gap of 7 and 14 days or more, respectively.ConclusionsPatients’ adherence was improved with low-cost and easily implemented interventions using existing health facilities’ resources. We recommend that such interventions be considered for scale-up at national levels as measures to improve clinic attendance and ART adherence among patients in Uganda and other low-resource settings in sub-Saharan Africa.

Early HIV disclosure and nondisclosure among men and women on antiretroviral treatment in Uganda

Efforts to expand access to HIV care and treatment often stress the importance of disclosure of HIV status to aid adherence, social support, and continued resource mobilization. We argue that an examination of disclosure processes early in the process of seeking testing and treatment can illuminate individual decisions and motivations, offering insight into potentially improving engagement in care and adherence. We report on baseline data of early HIV disclosure and nondisclosure, including reasons for and responses to disclosure from a cohort of men and women (n=949) currently accessing antiretroviral treatment in two regions of Uganda. We found early disclosures at the time of suspicion or testing positive for HIV by men and women to be largely for the purposes of emotional support and friendship. Responses to these selected disclosures were overwhelmingly positive and supportive, including assistance in accessing treatment. Nonetheless, some negative responses of worry, fear, or social ostracism did occur. Individuals deliberately chose to not disclose their status to partners, relatives, and others in their network, for reasons of privacy or not wanting to cause worry from the other person. These data demonstrate the strategic choices that individuals make early in the course of suspicion, testing, and treatment for HIV to mobilize resources and gain emotional or material support, and similarly their decisions and ability to maintain privacy regarding their status.

Rates and Predictors of Consistent Condom-use by People Living with HIV/AIDS on Antiretroviral Treatment in Uganda

Antiretroviral treatment (ART) has been recognized as one of the methods for reducing the risk of HIV transmission, and access to this is being rapidly expanded. However, in a generalized HIV epidemic, ART could increase unprotected sex by people living with HIV/AIDS (PHAs). This paper assessed the rates and predictors of consistent condom-use by sexually-active PHAs after initiating ART. The study used cross-sectional data on sexual behaviour of 269 sexually-active ART-experienced individuals (95 males and 174 females) aged 18 years and above. The results revealed that 65% (70% of men and 61% of women) used condom consistently after initiating ART. Consistent use of condom was more likely if PHAs had secondary- or tertiary-level education and had more than one sex partner in the 12 months preceding the study. However, PHAs were less likely to have used condom consistently if they worked in the informal and formal sectors, belonged to the medium- and high-income groups, and were married. PHAs, who were on ART for less than 1 year and 1-2 year(s), had a good self-perception of health, had a sexual partner who was HIV-negative or a partner with unknown HIV status, and desired to bear children, were also less likely to have used condom consistently. The paper concluded that, although the majority of PHAs consistently used condom, there was potential for unprotected sex by PHAs on ART.

Changes in sexual desires and behaviours of people living with HIV after initiation of ART: implications for HIV prevention and health promotion.

BackgroundAs immune compromised HIV sero-positive people regain health after initiating antiretroviral treatment (ART), they may seek a return to an active 'normal' life, including sexual activity. The aim of the paper is to explore the changing sexual desires and behaviour of people on ART in Uganda over a 30 month period.MethodsThis study employed longitudinal qualitative interviews with forty people starting ART. The participants received their ART, adherence education and counselling support from The AIDS Support Organisation (TASO). The participants were selected sequentially as they started ART, stratified by sex, ART delivery mode (clinic or home-based) and HIV progression stage (early or advanced) and interviewed at enrolment, 3, 6, 18 and 30 months of their ART use.ResultsSexual desire changed over time with many reporting diminished desire at 3 and 6 months on ART compared to 18 and 30 months of use. The reasons for remaining abstinent included fear of superinfection or infecting others, fear that engaging in sex would awaken the virus and weaken them and a desire to adhere to the counsellors' health advice to remain abstinent. The motivations for resumption of sexual activity were: for companionship, to obtain material support, social norms around marriage, desire to bear children as well as to satisfy sexual desires. The challenges for most of the participants were using condoms consistently and finding a suitable sexual partner (preferably someone with a similar HIV serostatus) who could agree to have a sexual relationship with them and provide for their material needs.ConclusionsThese findings point to the importance of tailoring counselling messages to the changing realities of the ART users' cultural expectations around child bearing, marriage and sexual desire. People taking ART require support so they feel comfortable to disclose their HIV status to sexual partners.

Stavudine Toxicity in Women is the Main Reason for Treatment Change in a 3-Year Prospective Cohort of Adult Patients Started on First-Line Antiretroviral Treatment in Uganda

In resource-limited settings, there are only a few antiretroviral treatment (ART) options. Our objective was to evaluate the reasons for first-line ART changes in resource-limited settings. Prospective research cohort of patients initiating ART between April 2004 and April 2005 in Kampala, Uganda. The main endpoint was the substitution of at least 1 drug included in the initial combination. Five hundred Fifty-nine patients initiated on ART, 70% were female, median CD4+ count 98 (21-163) cells per microliter, median HIV RNA log₁₀ 5.4 (5.0-5.8). 413 (74%) patients were started on stavudine, lamivudine, and nevirapine, and 146 (36%) on zidovudine, lamivudine and efavirenz. One hundred Forty-eight (26.5%) had at least one treatment change (incidence rate 14.3 per 100 person-years; confidence interval: 12.2 to 16.9). The main reason for first treatment change was drug toxicity (n = 91, 61.5%). Stavudine accounted for the majority of the toxicities that led to drug substitution (n = 76, 84%). In the multivariate analysis, being female (P = 0.011) and being stage 3-4 as compared with 1-2 at ART initiation were predictive of stavudine substitution (P = 0.05). There was no difference in virologic outcome in patients who changed due to toxicity compared with those who did not. The majority of the treatment changes were due to stavudine-related toxicity. Long-term stavudine use is less well tolerated in women.

Reconsidering the impact of conflict on HIV infection among women in the era of antiretroviral treatment scale-up in sub-Saharan Africa: a gender lens

As increasing international and local efforts focus on scaling up access to antiretroviral treatment (ART) in sub-Saharan Africa the United Nations High Commissioner for Refugees (UNHCR) Medecins Sans Frontieres and the Joint United Nations Program on HIV/AIDS have increasingly advocated that the lack of essential medicines in conflict settings including ART is a violation of human rights. HIV infection and armed conflict are disproportionately represented in sub-Saharan Africa with women and children experiencing the largest burden of harms and adverse health outcomes due to both HIV infection risk and impact of conflict. Given emerging disparities in access to ART among HIV-positive women in conflict zones there is an urgent need to reconsider the impact of conflict on HIV infection. Importantly recent evidence suggests that there may be a protective effect of armed conflict on HIV prevalence as a result of reduced mobility and urbanization disruption of sexual networks and decreased casual consensual sex. At the same time substantial evidence suggests an increased vulnerability to HIV in conflict settings among women and children due to widespread human rights violations rape as a weapon of war forced occupational exposure the need for women to turn to sex work to support themselves and their families (i.e. survival sex) and reduced access to HIV prevention and reproductive health services. Regardless inequitable access to ART scale up in conflict zones suggests a need to re-examine the complex relationship between conflict and HIV infection. (excerpt)

A Cluster-Randomised Trial to Compare Home-Based with Health Facility-Based Antiretroviral Treatment in Uganda: Study Design and Baseline Findings

The scale-up of antiretroviral therapy is progressing rapidly in Africa but with a limited evidence-base. We report the baseline results from a large pragmatic cluster-randomised trial comparing different strategies of ART delivery. The trial is integrated in normal health service delivery. 1453 subjects were recruited into the study. Significantly more women (71%) than men (29%) were recruited. The WHO HIV clinical stage at presentation did not differ significantly between men and women: 58% and 53% respectively were at WHO stage III or IV (p=0.9). Median CD4 counts (IQR) x 106cells/l were 98 (28, 160) among men and 111 (36, 166) among women. Sixty-four percent of women and 61% men had plasma viral load ≥100,000 copies. Baseline characteristics did not change over time. Considerably fewer men than women presented for treatment. Both men and women presented at an advanced stage with very low median CD4 count and high plasma viral load.