Introduction
Dolutegravir (DTG) has become a preferred component of first‐line antiretroviral therapy (ART) in many settings but may be associated with excess weight gain. We evaluated changes in ...weight and body mass index (BMI) after switch to single‐tablet tenofovir/lamivudine/dolutegravir (TLD) by people living with HIV (PLWH) in four African countries.
Methods
The African Cohort Study (AFRICOS) prospectively follows adults with and without HIV in Kenya, Uganda, Tanzania and Nigeria. Demographics, ART regimen, weight, BMI and waist‐to‐hip ratio were collected every 6 months. Multivariable Cox proportional hazards modelling was used to estimate hazard ratios and 95% confidence intervals (CIs) for factors associated with developing a BMI ≥25 kg/m2. Linear mixed effects models with random effects were used to examine the average change in BMI, weight and waist‐to‐hip ratio.
Results
From 23 January 2013 to 1 December 2020, 2950 PLWH were enrolled in AFRICOS and 1474 transitioned to TLD. In adjusted models, PLWH on TLD had 1.77 times the hazard of developing a high BMI (95% CI: 1.22–2.55) compared to PLWH on non‐TLD ART. Examining change in weight among all PLWH on ART, participants on TLD gained an average of 0.68 kg (95% CI: 0.32–1.04) more than PLWH on other regimens after adjusting for duration on ART, sex, age, study site and CD4 nadir. Among participants who switched to TLD, the average change in weight prior to TLD switch was 0.35 kg/year (95% CI: 0.25–0.46) and average change in weight was 1.46 kg/year (95% CI: 1.18–1.75) in the year following transition to TLD after adjustment for confounders.
Conclusions
Elevated BMI and weight gain among PLWH on TLD are concerning safety signals. Implications for the development of metabolic comorbidities should be monitored, particularly if annual weight gain persists during continued follow‐up after transitioning to TLD.
We hypothesized that total body weight (TBW) gain after switching antiretroviral therapy (ART) regimen to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) may negatively impact ART ...adherence and viral load (VL) and therefore sought to examine these associations.
The ongoing African Cohort Study (AFRICOS) enrols people with HIV at 12 facilities in Kenya, Nigeria, Tanzania and Uganda supported by The US President's Emergency Plan for AIDS Relief. Among ART-experienced participants who switched to TLD, we used multivariable multinomial logistic regression to examine associations between pre-/post-TLD changes in percentage TBW (≥5% gain, <5% change, ≥5% loss) and changes in self-reported ART adherence (0, 1-2, ≥3 days missed doses in past 30 days) and VL (<50 copies/mL (undetectable), 50-999 copies/mL (detectable, but suppressed), ≥1000 copies/mL (unsuppressed).
Among 1508 participants, median time from starting TLD to follow-up was 9 months (interquartile range: 7-11). Overall, 438 (29.1%) participants experienced a TBW gain ≥5%, which was more common among females than among males (32.2% vs 25.2%, p = 0.005) and participants switching from efavirenz 32.0% vs nevirapine (19.9%) and boosted protease inhibitor (20.0%); p < 0.001. Compared with a TBW change <5% 950 (63.0%) participants, TBW gain ≥5% was not significantly associated with more days with missed ART doses adjusted odds ratio (aOR) = 0.77, 95% confidence interval (CI): 0.48-1.23 or VL becoming detectable and/or unsuppressed (aOR = 0.69, 95% CI: 0.41-1.16).
Although a substantial proportion of participants experienced weight gain after switching to TLD, we did not identify a significant impact on adherence or virological outcomes.
Sexual stigma affecting MSM in Nigeria may be an important driver of HIV and other sexually transmitted infections (STIs), but potential mechanisms through which this occurs are not well understood. ...This study assessed the contributions of suicidal ideation and sexual risk behaviors to causal pathways between stigma and HIV/STIs.
Data were collected from the TRUST/RV368 Study, a prospective cohort of 1480 MSM from Abuja and Lagos, Nigeria.
Participants enrolled from March 2013 to February 2016 were classified into three stigma subgroups based on a latent class analysis of nine stigma indicators. Path analysis was used to test a model where disclosure led to stigma, then suicidal ideation, then condomless sex with casual sex partners, and finally incident HIV infection and/or newly diagnosed STIs, adjusting the model for age, education, having had female sex partners in the past 12 months, and sex position. Both direct and indirect (mediational) paths were tested for significance and analyses were clustered by city.
As stigma increased in severity, the proportion of incident HIV/STI infections increased in a dose-response relationship (low: 10.6%, medium: 14.2%, high 19.0%, P = 0.008). All direct relationships in the model were significant and suicidal ideation and condomless sex partially mediated the association between stigma and incident HIV/STI infection.
These findings highlight the importance of the meaningful integration of stigma-mitigation strategies in conjunction with mental health services as part of a broader strategy to reduce STI and HIV acquisitions among Nigerian MSM.
Preexposure prophylaxis (PrEP) is effective in preventing human immunodeficiency virus (HIV) infection among sexual and gender minorities (SGMs). We evaluated the characteristics associated with ...engagement in 7 steps of the PrEP cascade among SGMs in Nigeria.
Sexual and gender minorities without HIV from the Abuja site of TRUST/RV368 cohort who were surveyed on awareness of and willingness to use PrEP were approached for PrEP initiation upon availability of oral daily PrEP. To understand gaps in the uptake of oral daily PrEP, we categorized the HIV PrEP cascade as (i) education about PrEP, (ii) interest in PrEP, (iii) successful contact, (iv) appointment scheduled, (v) appointment attendance, (vi) PrEP initiation, and (vii) plasma protective levels of tenofovir disoproxil fumarate. Multivariable logistic regression models were used to determine factors associated with each of the 7 steps in the HIV PrEP cascade.
Of 788 participants, 718 (91.1%) showed interest in taking oral daily PrEP every day and/or after a sexual act, 542 (68.8%) were successfully contacted, 433 (54.9%) scheduled an appointment, 409 (51.9%) attended a scheduled appointment, 400 (50.8%) initiated oral daily PrEP, and 59 (7.4%) had protective levels of tenofovir disoproxil fumarate. Of initiators of PrEP, 23 (5.8%) seroconverted at a rate of 13.9 cases/100 person-years. Better social support, larger network density, and higher education were associated with engagement in 4 to 5 components of the cascade.
Our data highlight a gap between willingness and actual PrEP use. Despite PrEP's effectiveness in preventing HIV, the optimal impact of PrEP for SGMs in sub-Saharan Africa will require multifaceted approaches that combine social support, education, and destigmatization.
Earlier antiretroviral therapy (ART) may decrease progression to advanced HIV disease (AHD) with CD4 count of <200 cells per cubic millimeter or clinical sequelae. We assessed factors associated with ...AHD among people living with HIV before and during the "test and treat" era.
The African Cohort Study prospectively enrolls adults with and without HIV from 12 clinics in Uganda, Kenya, Tanzania, and Nigeria.
Enrollment evaluations included clinical history, physical examination, and laboratory testing. Generalized estimating equations were used to estimate adjusted odds ratios and 95% confidence intervals for factors associated with CD4 count of <200 cells per cubic millimeter at study visits.
From 2013 to 2021, 3059 people living with HIV with available CD4 at enrollment were included; median age was 38 years interquartile range: 30-46 years, and 41.3% were men. From 2013 to 2021, the prevalence of CD4 count of <200 cells per cubic millimeter decreased from 10.5% to 3.1%, whereas the percentage on ART increased from 76.6% to 100% ( P <0.001). Factors associated with higher odds of CD4 count of <200 cells per cubic millimeter were male sex (adjusted odds ratio 1.56 confidence interval: 1.29 to 1.89), being 30-39 years (1.42 1.11-1.82) or older (compared with <30), have World Health Organization stage 2 disease (1.91 1.48-2.49) or higher (compared with stage 1), and HIV diagnosis eras 2013-2015 (2.19 1.42-3.37) or later (compared with <2006). Compared with ART-naive, unsuppressed participants, being viral load suppressed on ART, regardless of ART duration, was associated with lower odds of CD4 count of <200 cells per cubic millimeter (<6 months on ART: 0.45 0.34-0.58).
With ART scale-up, AHD has declined. Efforts targeting timely initiation of suppressive ART may further reduce AHD risk.
Background. Elite controllers spontaneously suppress human immunodeficiency virus (HIV) viremia but also demonstrate chronic inflammation that may increase risk of comorbid conditions. We compared ...hospitalization rates and causes among elite controllers to those of immunologically intact persons with medically controlled HIV. Methods. For adults in care at 11 sites from 2005 to 2011, person-years with CD4 T-cell counts ≥350 cells/mm² were categorized as medical control, elite control, low viremia, or high viremia. All-cause and diagnostic categoryspecific hospitalization rates were compared between groups using negative binomial regression. Results. We identified 149 elite controllers (0.4%) among 34 354 persons in care. Unadjusted hospitalization rates among the medical control, elite control, low-viremia, and high-viremia groups were 10.5, 23.3, 12.6, and 16.9 per 100 person-years, respectively. After adjustment for demographic and clinical factors, elite control was associated with higher rates of all-cause (adjusted incidence rate ratio, 1.77 95% confidence interval, 1.21-2.60), cardiovascular (3.19 1.50-6.79) and psychiatric (3.98 1.54-10.28) hospitalization than was medical control. Non-AIDS-defining infections were the most common reason for admission overall (24.1% of hospitalizations) but were rare among elite controllers (2.7%), in whom cardiovascular hospitalizations were most common (31.1%). Conclusions. Elite controllers are hospitalized more frequently than persons with medically controlled HIV and cardiovascular hospitalizations are an important contributor.
Cervical cancer is a common preventable cancer among African women living with HIV (WLWH). Molecular diagnostics for high-risk human papillomavirus (HR-HPV) genotypes are standard components of ...cervical cancer screening in resource-rich countries but not in resource-limited settings. We evaluated HR-HPV genotypes among women with and without HIV in four African countries to inform cervical cancer preventive strategies.
The African Cohort Study (AFRICOS) enrolled participants with and without HIV at 12 clinics in Tanzania, Kenya, Uganda, and Nigeria. Cervical cytobrush specimens from women were genotyped for 14 HR-HPV types using the multiplex Seegene Anyplex real-time PCR assay. Robust Poisson regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for factors associated with HR-HPV in WLWH.
From January 2015 to March 2020, 868 WLWH and 134 women living without HIV (WLWoH) were tested for HR-HPV with prevalence of 50.9 and 38.1%, respectively ( P = 0.007). Among WLWH, 844 (97.4%) were antiretroviral therapy (ART)-experienced and 772 (89.7%) virally suppressed 1000 copies/ml or less. The most frequent HR-HPV types among WLWH were HPV-16 (13.5%), HPV-52 (9.5%), and HPV-35 (9.3%). HR-HPV infection was more common among Tanzanian WLWH (adjusted RR: 1.23, 95% CI 1.05-1.44, P = 0.012). Also, WLWH with CD4 + T cells of less than 200 cell/μl had 1.51-fold increased risk of having HR-HPV (95% CI 1.23-1.86, P < 0.001).
HR-HPV was common in WLWH in four African countries, particularly among women with low CD4 + cell count. Scale up of HPV vaccines and development of vaccines with broader activity against less common HR-HPV types may improve cervical cancer prevention in Africa.
We estimated the effects of cumulative exposure to depressive symptoms on risk of all-cause mortality among people with HIV (PWH) in four African countries.
An analysis of prospective cohort data.
...The African Cohort Study (AFRICOS) is a prospective cohort of people receiving care at twelve clinics in Kenya, Nigeria, Tanzania, and Uganda. Every 6 months from January 2013 to May 2020, participants underwent laboratory monitoring, structured surveys, and assessment of depressive symptom severity using the Center for Epidemiologic Studies Depression Scale (CES-D). All-cause mortality was the outcome of interest. The predictor of interest was a time-updated measure of the percentage of days lived with depression (PDD). Marginal structural Cox proportional hazards regression models were used, adjusting for potential confounders including time-varying alcohol use, drug use, and viral load.
Among 2520 enrolled participants, 1479 (59%) were women and the median age was 38 (interquartile range IQR: 32-46). At enrollment, 1438 (57%) were virally suppressed (<200 copies/ml) and 457 (18%) had CES-D at least 16, indicating possible depression. Across 9093 observed person-years, the median PDD was 0.7% (IQR: 0-5.9%) with 0.8 deaths per 100 person-years. Leading causes of death included cancer (18% of deaths) and accidents (14%). Models suggested that each 25% absolute increase in PDD was associated with a 69% increase in the risk of all-cause mortality (hazard ratio: 1.69; 95% confidence interval: 1.18-2.43).
Cumulative exposure to depressive symptoms was substantially associated with the risk of mortality in this cohort of PWH in Africa.
Although sexual stigma has been linked to decreased HIV testing among men who have sex with men (MSM), mechanisms for this association are unclear. We evaluated the role of psychosocial well-being in ...connecting sexual stigma and HIV testing using an explanatory sequential mixed methods analysis of 25 qualitative and 1480 quantitative interviews with MSM enrolled in a prospective cohort study in Nigeria from March/2013–February/2016. Utilizing structural equation modeling, we found a synergistic negative association between sexual stigma and suicidal ideation on HIV testing. Qualitatively, prior stigma experiences often generated psychological distress and perceptions of feeling unsafe, which decreased willingness to seek services at general health facilities. MSM reported feeling safe at the MSM-friendly study clinic but still described a need for psychosocial support services. Addressing stigma and unmet mental health needs among Nigerian MSM has the potential to improve HIV testing uptake.
•HIV and malaria remain important concerns with major global health implications.•Co-infection can cause hematologic abnormalities and greater morbidity in Africa.•The prevalence of asymptomatic ...malaria was highest in Uganda and Western Kenya.•Asymptomatic malaria was common and impacted hematologic parameters.•Anemia was more likely among people living with HIV.
HIV and malaria coinfection impacts disease management and clinical outcomes. This study investigated hematologic abnormalities in malaria-asymptomatic people living with HIV (PLHIV) in regions with differing malaria transmission.
Study participants were enrolled in the African Cohort Study: two sites in Kenya, one in Uganda, and one in Nigeria. Data was collected at enrollment and every 6 months. Logistic regression estimated odds ratios for associations between HIV/malaria status and anemia, thrombocytopenia, and leucopenia.
Samples from 1587 participants with one or more visits comprising 1471 (92.7%) from PLHIV and 116 (7.3%) without HIV were analyzed. Parasite point prevalence significantly differed across the study sites (P <0.001). PLHIV had higher odds of anemia, with males at lower odds compared to females; the odds of anemia decreased with age, reaching significance in those ≥50 years old. Participants in Kisumu, Kenya had higher odds of anemia compared to other sites. PLHIV had higher odds of leucopenia, but malaria co-infection was not associated with worsened leucopenia. The odds of thrombocytopenia were decreased in HIV/malaria co-infection compared to the uninfected group.
Hematological parameters are important indicators of health and disease. In PLHIV with asymptomatic malaria co-infection enrolled across four geographic sites in three African countries, abnormalities in hematologic parameters differ in different malaria transmission settings and are region-specific.
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