Determinants of Mortality and Loss to Follow-Up among Adults Enrolled in HIV Care Services in Rwanda

Background

Antiretroviral therapy (ART) improves morbidity and mortality in patients with HIV, however high rates of loss to follow-up (LTF) and mortality have been documented in HIV care and treatment programs.

Methods

We analyzed routinely-collected data on HIV-infected patients ≥15 years enrolled at 41 healthcare facilities in Rwanda from 2005 to 2010. LTF was defined as not attending clinic in the last 12 months for pre-ART patients and 6 months for ART patients. For the pre-ART period, sub-distribution hazards models were constructed to estimate LTF and death to account for competing risks. Kaplan-Meier (KM) and Cox proportional hazards models were used for patients on ART.

Results

31,033 ART-naïve adults were included, 64% were female and 75% were WHO stage I or II at enrollment. 17,569 (56%) patients initiated ART. Pre-ART competing risk estimates of LTF at 2 years was 11.2% (95%CI, 10.9–11.6%) and 2.9% for death (95%CI 2.7–3.1%). Among pre-ART patients, male gender was associated with higher LTF (adjusted sub-hazard ratio (aSHR) 1.3, 95%CI 1.1–1.5) and death (aSHR 1.7, 95%CI 1.4–2.1). Low CD4 count (CD4<100 vs. ≥350 aSHR 0.2, 95%CI 0.1–0.3) and higher WHO stage (WHO stage IV vs. stage I aSHR 0.4, 95%CI 0.2–0.6) were protective against pre-ART LTF. KM estimates for LTF and death in ART patients at 2 years were 4.4% (95%CI 4.4–4.5%) and 6.3% (95%CI 6.2–6.4%). In patients on ART, male gender was associated with LTF (adjusted hazard ratio (AHR) 1.4, 95%CI 1.2–1.7) and death (AHR1.3, 95%CI 1.2–1.5). Mortality was higher for ART patients ≥40 years and in those with lower CD4 count at ART initiation.

Conclusions

Low rates of LTF and death were founds among pre-ART and ART patients in Rwanda but greater efforts are needed to retain patients in care prior to ART initiation, particularly among those who are healthy at enrollment.     

A Phase I Double Blind,Placebo-Controlled,Randomized Study of the Safety and Immunogenicity of Electroporated HIV DNA with or without Interleukin 12 in Prime-Boost Combinations with an Ad35 HIV Vaccine in Healthy HIV-Seronegative African Adults

Background

Strategies to enhance the immunogenicity of DNA vaccines in humans include i) co-administration of molecular adjuvants, ii) intramuscular administration followed by in vivo electroporation (IM/EP) and/or iii) boosting with a different vaccine. Combining these strategies provided protection of macaques challenged with SIV; this clinical trial was designed to mimic the vaccine regimen in the SIV study.

Methods

Seventy five healthy, HIV-seronegative adults were enrolled into a phase 1, randomized, double-blind, placebo-controlled trial. Multi-antigenic HIV (HIVMAG) plasmid DNA (pDNA) vaccine alone or co-administered with pDNA encoding human Interleukin 12 (IL-12) (GENEVAX IL-12) given by IM/EP using the TriGrid Delivery System was tested in different prime-boost regimens with recombinant Ad35 HIV vaccine given IM.

Results

All local reactions but one were mild or moderate. Systemic reactions and unsolicited adverse events including laboratory abnormalities did not differ between vaccine and placebo recipients. No serious adverse events (SAEs) were reported. T cell and antibody response rates after HIVMAG (x3) prime—Ad35 (x1) boost were independent of IL-12, while the magnitude of interferon gamma (IFN-γ) ELISPOT responses was highest after HIVMAG (x3) without IL-12. The quality and phenotype of T cell responses shown by intracellular cytokine staining (ICS) were similar between groups. Inhibition of HIV replication by autologous T cells was demonstrated after HIVMAG (x3) prime and was boosted after Ad35. HIV specific antibodies were detected only after Ad35 boost, although there was a priming effect with 3 doses of HIVMAG with or without IL-12. No anti-IL-12 antibodies were detected.

Conclusion

The vaccines were safe, well tolerated and moderately immunogenic. Repeated administration IM/EP was well accepted. An adjuvant effect of co-administered plasmid IL-12 was not detected.

Trial Registration

ClinicalTrials.gov NCT01496989     

High burden of prevalent and recently acquired HIV among female sex workers and female HIV voluntary testing center clients in Kigali, Rwanda

Objectives

To estimate HIV prevalence and risk factors in population-based samples of female sex workers (FSW) and female voluntary counseling and testing (VCT) clients in Rwanda.

Methods

We conducted a cross-sectional survey of 800 FSW and 1,250 female VCT clients in Rwanda, which included interviewing and testing for HIV-1/2, HSV-2 and pregnancy, and BED-CEIA and Avidity Index (AI) to identify recent infections among HIV-infected women.

Results

Prevalence of HIV-1, HSV-2, and pregnancy were 24% (95% CI: 21.0–27.0), 59.8% (56.4–63.2), and 7.6% (5.8–9.5) among FSW, and 12.8% (10.9–14.6), 43.2% (40.4–46.0), and 11.4% (9.7–13.3) among VCT clients, respectively. Thirty-five percent of FSW and 25% of VCT clients had never been HIV tested. Per national guidelines, 33% of newly HIV-diagnosed FSW and 36% of VCT clients were already eligible for ART based on CD4<350 cells/µl. Condom use at last sex was higher among FSW (74%) than VCT clients (12%). In age and district of residence-adjusted models, HIV-1 seropositivity was associated with HSV-2 co-infection; recent treatment for sexually transmitted infection (STI); genital symptoms; forced sex; imprisonment; widowhood; and alcohol consumption. Eleven percent of FSW and 12% of VCT clients had recently acquired HIV-1 per BED-CEIA and AI. HSV-2 infection and recent STI treatment were associated with recent HIV infection in both groups, and being married and vaginal cleansing were associated with recent infection before last sex among VCT clients.

Conclusions

This population-based survey reveals a high HIV prevalence and incidence among FSW and female VCT clients in Kigali, the scale of which is masked by the low general-population HIV prevalence in Rwanda. HIV/STI and family planning services should be strengthened.     

PrePex Male Circumcision: Follow-Up and Outcomes during the First Two Years of Implementation at the Rwanda Military Hospital

Background

PrePex Male Circumcision (MC) has been demonstrated as an effective and scalable strategy to prevent HIV infection in low- and middle-income countries. This study describes the follow-up and outcomes of clients who underwent PrePex MC between January 2011 and December 2012 with weekly follow-up at the Rwanda Military Hospital, the first national hospital in Rwanda to adopt PrePex.

Methods

Data on570 clients age 21 to 54 were extracted from patient records. We compared socio-demographic and clinical characteristics, the operator''s qualification, HIV status, pain before and after device removal, urological status, device size and follow-up time between clients who were formally discharged and those who defaulted. We reported bivariate associations between each covariate and discharge status, number of people with adverse events by discharge status, and time to formal discharge or defaulting using life table methods. Data were entered into Epidata and analyzed with Stata v13.

Results

Among study participants, 96.5% were circumcised by non-physician operators, 85.4%were under 30years, 98.9% were HIV-negative and 97.9% were without any urological problems that could delay the healing time. Most (70.7%) defaulted before formal discharge. Pain before (p<0.001) and after PrePex device removal (p = 0.001) were associated with discharge status, although very few cases were reported, and pain was more commonly missing among defaulters. Twenty-seven adverse events were reported (7 formally discharged, 20 defaulters). Median follow-up time was seven weeks among formally discharged and six weeks among defaulters (p<0.001).

Conclusion

Given that all socio-demographic and most clinical characteristics were not associated with defaulting, we hypothesize that clients stopped returning once they determined they were healed. We recommend less frequent follow-up protocols to encourage clinical visits until formal discharge. Based on these results and recommendations, we believe PrePex MC is a practical circumcision strategy in Rwanda and in sub-Saharan Africa.     

A new Parakneria Poll 1965 (Gonorhynchiformes: Kneriidae), ‘Mikinkidi’ from the Upper Lufira Basin (Upper Congo: DRC): Evidence from a morphologic and DNA barcoding integrative approach

A new species, Parakneria alytogrammus, is described from the main stream of the Upper Lufira River. This species is easily distinguished from its congeners from the Congo Basin by its unique colouration, consisting of a low number of transversal bands on each of the caudal-fin lobes, 2 (vs. 3–5) and the presence of an uninterrupted lateral mid-longitudinal black band in fresh and preserved specimens (vs. absent). In addition, the new species differs from its Upper Lualaba congeners by the narrow width of its pectoral-fin base, 4.8–5.6% L_S [vs. wider, 8.2–10.1% for P. lufirae, 8.6% L_S for P. damasi (holotype), and 7.6–7.9% L_S for P. thysi]. Finally, it differs from the only species currently known from the Luapula-Mweru system, P. malaissei, by having a short post-dorsal distance, 36.4–36.6% L_S (vs. longer, 38.6–41.1% L_S) and a short post-pelvic distance of 40.0–40.6% L_S (vs. longer, 41.4–44.1% L_S). Mitochondrial DNA-haplotypes of P. alytogrammus sp. nov. form a clade, which is sister to the P. thysi clade, and from which it diverges by a genetic (Kimura 2-parameter and uncorrected p) distance of 0.7% in the COI-barcoding locus. The Upper Lufira, one of the sub-basins of the Upper Congo Basin, remains poorly explored relative to its fish fauna. In contrast, the region is well explored with regard to its mineral wealth. Unfortunately, mining exploitation is carried out in the region without proper concern for the environment. Thus, the discovery of this new species for science calls for increased protection and aquatic biodiversity exploration in this mining region.