Trends in body mass index in the pre-dolutegravir period in South Africa.

Background: Antiretroviral therapy (ART) is associated with weight gain, but this has been shown to be more marked with dolutegravir and other integrase strand transfer inhibitors. Objectives: We studied weight gain in people living with HIV (PLWH) on ART compared to the general population in the period before dolutegravir was introduced in a rural South African cohort. Method: Longitudinal analysis of the Ndlovu Cohort Study including 36-48 months' follow-up data. From 2014 to 2019, data were collected annually in Limpopo, rural South Africa. Linear mixed models using HIV status, demographics, ART use and cardiovascular risk factors were used to estimate trends in body mass index (BMI) over time. Results: In total, 1518 adult, non-pregnant participants were included, of whom 518 were PLWH on ART (79.8%), 135 PLWH not yet on ART (20.2%) and 865 HIV-negative. HIV-negative participants had significantly higher BMIs than PLWH on ART at all study visits. There was a significant increase in BMI in all subgroups after 36 months (PLWH on ART, BMI +1.2 kg/m2, P < 0.001; PLWH not on ART, BMI +1.8 kg/m2, P < 0.001 and HIV-negative, BMI +1.3 kg/m2, P < 0.001). Conclusion: The increase in BMI in PLWH and HIV-negative participants is a serious warning signal as obesity results in morbidity and mortality.

Immune activation correlates with and predicts CXCR4 co-receptor tropism switch in HIV-1 infection.

HIV-1 cell entry is mediated by binding to the CD4-receptor and chemokine co-receptors CCR5 (R5) or CXCR4 (X4). R5-tropic viruses are predominantly detected during early infection. A switch to X4-tropism often occurs during the course of infection. X4-tropism switching is strongly associated with accelerated disease progression and jeopardizes CCR5-based HIV-1 cure strategies. It is unclear whether host immunological factors play a causative role in tropism switching. We investigated the relationship between immunological factors and X4-tropism in a cross-sectional study in HIV-1 subtype C (HIV-1C)-infected patients and in a longitudinal HIV-1 subtype B (HIV-1B) seroconverter cohort. Principal component analysis identified a cluster of immunological markers (%HLA-DR+ CD4+ T-cells, %CD38+HLA-DR+ CD4+ T-cells, %CD38+HLA-DR+ CD8+ T-cells, %CD70+ CD4+ T-cells, %CD169+ monocytes, and absolute CD4+ T-cell count) in HIV-1C patients that was independently associated with X4-tropism (aOR 1.044, 95% CI 1.003-1.087, p = 0.0392). Analysis of individual cluster contributors revealed strong correlations of two markers of T-cell activation (%HLA-DR+ CD4+ T-cells, %HLA-DR+CD38+ CD4+ T-cells) with X4-tropism, both in HIV-1C patients (p = 0.01;p = 0.03) and HIV-1B patients (p = 0.0003;p = 0.0001). Follow-up data from HIV-1B patients subsequently revealed that T-cell activation precedes and independently predicts X4-tropism switching (aHR 1.186, 95% CI 1.065-1.321, p = 0.002), providing novel insights into HIV-1 pathogenesis and CCR5-based curative strategies.

The effects of a physiotherapist-led exercise intervention on peripheral neuropathy among people living with HIV on antiretroviral therapy in Kigali, Rwanda.

BACKGROUND: HIV-associated peripheral neuropathy (PN) is common in people living with HIV. Its management is mostly symptomatic utilising pharmacological approaches. OBJECTIVES: This study determined the effects of an exercise intervention on PN among Rwandan people living with HIV receiving antiretroviral therapy (ART). METHODS: A 12-week single-blinded randomised controlled trial using the Brief Peripheral Neuropathy Screen (BPNS) as the assessment tool tested the effects of an exercise intervention on PN, followed by a 12-week non-intervention period. A total of 120 people with HIV- associated PN on ART were randomised to an exercise or no exercise group. Both groups continued receiving routine care. A bivariate analysis using Pearson's chi-square test for significant differences in PN symptoms and signs, between groups, at baseline, after the 12 weeks intervention and 12 weeks post-intervention using generalised linear regression models to determine predictors of treatment outcomes was undertaken, utilising an intention-to-treat analysis (alpha p ≤ 0.05). RESULTS: At 12 weeks, the intervention group compared to the control: neuropathic pain 70% versus 94% (p < 0.005), PN symptoms severity - mild and/or none in 85% versus 60% (p < 0.001) and radiation of PN symptoms reduced, 80% versus 37% (p < 0.001). There were no differences in PN signs at 12 weeks intervention and at 12 weeks post-intervention. Having changed the antiretroviral (ARV) and having developed PN symptoms after the start on ARVs predicted treatment improvement, while demographic factors did not predict any treatment outcome. CONCLUSION: A physiotherapist-led exercise intervention improved PN symptoms, but with non-significant improvement in PN signs. Factors related to early diagnosis and treatment of PN were facilitators for the improvement of PN symptoms. CLINICAL IMPLICATIONS: Physiotherapist-led exercises should be integrated into the routine management of people living with HIV on ART with PN symptoms.

Over-reported peripheral neuropathy symptoms in a cohort of HIV infected and uninfected Rwandan women: the need for validated locally appropriate questionnaires.

BACKGROUND: Peripheral neuropathy symptoms (PNS) are commonly manifested in HIV-infected (HIV+) individuals, although data are limited on the prevalence and predictors of PNS in HIV+ patients from sub-Saharan Africa. OBJECTIVE: To determine the prevalence and predictors of PNS in HIV+ and HIV-uninfected (HIV-) Rwandan women. METHODS: Data were analysed from 936 (710 HIV+ and 226 HIV-) women from the Rwanda Women Interassociation Study and Assessment (RWISA), an observational prospective cohort study investigating the effectiveness and toxicity of ART in HIV+ women. RESULTS: Of 936 enrolled, 920 (98.3%) were included in this analysis with 44% of HIV- and 52% of the HIV+ women reporting PNS (p=0.06). CD4+ count was not associated with PNS, although there was a non-significant trend towards higher prevalence in those with lower CD4+ counts. For the HIV- women, only alcohol and co-trimoxazole use were independently associated with PNS. WHO HIV stage IV illness and albumin ≤ 3.5 were associated with PNS in HIV+ women. CONCLUSIONS: The rate of peripheral neuropathy symptoms reported in this cohort of HIV-infected African women seems implausible, and rather suggests that the screening tool for peripheral neuropathy in culturally diverse African settings be locally validated.

Tuberculosis case finding: evaluation of a paper slip method to trace contacts.

SETTING: South Africa has the third highest tuberculosis (TB) burden in the world. Intensified case finding, recommended by WHO, is one way to control TB. OBJECTIVE: To evaluate the effectiveness and acceptability of a paper slip method for TB contact tracing. METHOD: TB patients were offered paper slips to give to their contacts, inviting them for TB screening. The number of contacts screened and the proportion diagnosed with TB was calculated. Contacts that returned to the clinic after receiving the slips were interviewed. A focus group discussion (FGD) with TB patients was held to determine their acceptability. RESULTS: From 718 paper slips issued, a 26% TB contact tracing rate was found, with a 12% case detection rate. The majority (68%) of contacts were screened within 2 weeks of receiving the slip. Age and gender were not significantly associated with time to screening. 16% of the contacts screened did not reside with the TB patients. 98% of the contacts said the method was acceptable. FGD findings show that this method is acceptable and may prevent stigma associated with TB/HIV. CONCLUSION: This simple, inexpensive method yields high contact tracing and case detection rates and potentially would yield additional benefits outside households.

Efavirenz use during pregnancy and for women of child-bearing potential.

BACKGROUND: Efavirenz is the preferred non-nucleoside reverse transcriptase inhibitor for first-line antiretroviral treatment in many countries. For women of childbearing potential, advantages of efavirenz are balanced by concerns that it is teratogenic. This paper reviews evidence of efavirenz teratogenicity and considers implications in common clinical scenarios. FINDINGS: Concerns of efavirenz-induced fetal effects stem from animal studies, although the predictive value of animal data for humans is unknown. Four retrospective cases of central nervous system birth defects in infants with first trimester exposure to efavirenz have been interpreted as being consistent with animal data. In a prospective pregnancy registry, which is subject to fewer potential biases, no increase was detected in overall risk of birth defects following exposure to efavirenz in the first-trimester. DISCUSSION: For women planning a pregnancy or not using contraception, efavirenz should be avoided if alternatives are available. According to WHO guidelines for resource-constrained settings, benefits of efavirenz are likely to outweigh risks for women using contraception. Women who become pregnant while receiving efavirenz often consider drug substitution or temporarily suspending treatment. Both options have substantial risks for maternal and fetal health which, we argue, appear unjustified after the critical period of organogenesis (3-8 weeks post-conception). Efavirenz-based triple regimens, initiated after the first trimester of pregnancy and discontinued after childbirth, are potentially an important alternative for reducing mother-to-child transmission in pregnant women who do not yet require antiretroviral treatment. CONCLUSION: Current recommendations for care for women who become pregnant while receiving efavirenz may need to be re-considered, particularly in settings with limited alternative drugs and laboratory monitoring. With current data limitations, additional adequately powered prospective studies are needed.